Steroids, Fluorinated
Steroids, Chlorinated
Steroid Hydroxylases
Steroids
Procollagen-Proline Dioxygenase
Mixed Function Oxygenases
Hypoxia-Inducible Factor-Proline Dioxygenases
Hydroxylation
Hypoxia-Inducible Factor 1, alpha Subunit
Ketoglutaric Acids
Alkane 1-Monooxygenase
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Aldehyde Oxidase
Gonadal Steroid Hormones
Dioxygenases
Receptors, Steroid
Cytochrome P-450 Enzyme System
Phenylalanine Hydroxylase
Cholestanetriol 26-Monooxygenase
Hypoxia-Inducible Factor 1
Tryptophan Hydroxylase
Xanthine Dehydrogenase
Molybdenum
Methylococcus
Amino Acids, Dicarboxylic
Von Hippel-Lindau Tumor Suppressor Protein
Oxygen
Molecular Sequence Data
Alkanes
Amino Acid Sequence
Steroid 21-Hydroxylase
Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls. (1/1365)
Induction of cytochrome P450 isoforms, specifically CYP1A1, and their catalytic activities are potential biomarkers of environmental contamination by polychlorinated biphenyls (PCBs). In this study, dogs were exposed to 25 ppm or 5 ppm Aroclor 1248 (PCB mixture) daily in their diet for 10 or 20 weeks, respectively. Relative to controls, hepatic microsomes from dogs dosed with PCBs had higher levels of CYP1A1 detected in immunoblots and higher levels of EROD activity, but low levels of induction for CYP2B and PROD activity. Concentrations of 96 PCB congeners in serum and liver were evaluated using capillary chromatography. Results showed that all dogs exposed to PCB mixtures had higher levels of PCB in serum and liver. Dogs preferentially sequestered highly chlorinated PCB congeners in liver relative to serum. With these experiments, we demonstrated that EROD activity was a potentially sensitive marker of PCB exposure at 5 and 25 ppm. Furthermore, CYP1A1 and EROD activity were maximally induced in dogs consuming dietary concentrations only 2.5 times the maximal permissible level for human food (FDA). The value of CYP1A1 induction as a biomarker of PCB exposure was tenuous because neither CYP1A1 levels nor EROD activity correlated with total PCB body burden. However, a small subset of congeners were identified in liver that may strongly influence EROD and PROD induction. Finally, two dogs in the 25 ppm dose group were fasted for 48 h. After 24 h of fasting, several new congeners appeared in the serum and remained in the serum for the remainder of the fast. The fast caused a 293% increase in PCB concentration in serum. This increase has strong implications regarding mobilization of toxic PCBs in wildlife during fasting (e.g., migration, hibernation). (+info)An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (2/1365)
Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease. (+info)Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine. (3/1365)
Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model. (+info)Expression of 25(OH)D3 24-hydroxylase in distal nephron: coordinate regulation by 1,25(OH)2D3 and cAMP or PTH. (4/1365)
Previous studies using microdissected nephron segments reported that the exclusive site of renal 25-hydroxyvitamin D3-24-hydroxylase (24OHase) activity is the renal proximal convoluted tubule (PCT). We now report the presence of 24OHase mRNA, protein, and activity in cells that are devoid of markers of proximal tubules but express characteristics highly specific for the distal tubule. 24OHase mRNA was undetectable in vehicle-treated mouse distal convoluted tubule (DCT) cells but was markedly induced when DCT cells were treated with 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. 24OHase protein and activity were also identified in DCT cells by Western blot analysis and HPLC, respectively. 8-Bromo-cAMP (1 mM) or parathyroid hormone [PTH-(1-34); 10 nM] was found to potentiate the effect of 1, 25(OH)2D3 on 24OHase mRNA. The stimulatory effect of cAMP or PTH on 24OHase expression in DCT cells suggests differential regulation of 24OHase expression in the PCT and DCT. In the presence of cAMP and 1, 25(OH)2D3, a four- to sixfold induction in vitamin D receptor (VDR) mRNA was observed. VDR protein, as determined by Western blot analysis, was also enhanced in the presence of cAMP. Transient transfection analysis in DCT cells with rat 24OHase promoter deletion constructs demonstrated that cAMP enhanced 1, 25(OH)2D3-induced 24OHase transcription but this enhancement was not mediated by cAMP response elements (CREs) in the 24OHase promoter. We conclude that 1) although the PCT is the major site of localization of 24OHase, 24OHase mRNA and activity can also be localized in the distal nephron; 2) both PTH and cAMP modulate the induction of 24OHase expression by 1,25(OH)2D3 in DCT cells in a manner different from that reported in the PCT; and 3) in DCT cells, upregulation of VDR levels by cAMP, and not an effect on CREs in the 24OHase promoter, is one mechanism involved in the cAMP-mediated modulation of 24OHase transcription. (+info)Analysis of RNA-protein interactions of mouse liver cytochrome P4502A5 mRNA. (5/1365)
In our previous studies we have identified a 37/39 kDa, pyrazole-inducible, cytochrome P4502A5 (CYP2A5) mRNA binding protein and provided evidence that it may play a role in the stabilization and processing of the RNA [Geneste, Rafalli and Lang (1996) Biochem. J. 313, 1029-1037; Thulke-Gross, Hergenhahn, Tilloy-Ellul, Lang and Bartsch (1998) Biochem. J. 331, 473-481]. Details of the RNA-protein interactions are, however, not known. In this report we have performed an analysis of the interaction between the CYP2A5 mRNA and the 37/39 kDa protein. With UV-cross linking experiments, using RNA probes corresponding to various parts of the CYP2A5 mRNA, and with antisense oligonucleotides complementary to certain areas of the 3'-untranslated region (3'UTR), we could map the primary binding site to the tip of a 71 nt hair-pin loop at the 3'-UTR. This analysis also showed that the protein may have more than one site of interaction with the RNA and/or that, within the binding region, there could be more than one protein molecule binding to the RNA. Analysis of the probable conformations of the various probes used in the UV cross-linking experiments, in combination with the estimated binding affinities of the protein to the different probes, suggests that important factors in the high-affinity binding are the UAG triplet flanked by GA-rich sequences at the tip of the hair-pin loop, in addition to the conformation of the loop itself. Within the binding region, similarities with known binding sites of heterogeneous nuclear ribonucleoprotein (hnRNP) A1 in other RNA molecules were revealed by sequence alignment analysis. Moreover, competition experiments with an oligoribonucleotide corresponding to a known high-affinity binding site of hnRNP A1, and immunoprecipitation of the UV cross-linked 37/39 kDa complex showed that the protein binding to the CYP2A5 mRNA could be hnRNP A1 or its close analogue. It was also shown that the 37/39 kDa protein binds with less affinity to CYP2A4 mRNA than to CYP2A5 mRNA. This is in accordance with experiments characterizing the binding site, since these two otherwise highly homologous genes are kown to have a three nucleotide difference within the region important for the high binding affinity. Since the response of CYP2A4 to pyrazole is known to be weak, as compared with CYP2A5, this observation provides further evidence for a regulatory role of the 37/39 kDa protein in CYP2A5 mRNA metabolism. (+info)Competition between cytochrome P-450 isozymes for NADPH-cytochrome P-450 oxidoreductase affects drug metabolism. (6/1365)
NADPH-cytochrome P-450 oxidoreductase (CPR) is essential for the catalytic activity of cytochrome P-450 (P-450). On a molar basis, the amount of P-450 exceeds that of CPR in human liver. In this study, we investigated whether drug-drug interactions can occur as a result of competition between P-450 isozymes for this ancillary protein. For this purpose, combinations of P-450 isozymes were coexpressed together with P-450 reductase in Escherichia coli. We show that testosterone inhibited the CYP2D6-mediated bufuralol 1'-hydroxylase activity in bacterial membranes containing both CYP2D6 and CYP3A4 but not in membranes containing CYP2D6 alone. Conversely, bufuralol inhibited the CYP3A4-mediated testosterone 6beta-hydroxylase activity in bacterial membranes containing both CYP3A4 and CYP2D6 but not in membranes containing only CYP3A4. In each case, inhibition was seen even at a P-450 to P-450 reductase ratio of 1.9:1, which is more favorable than the ratio of 4 reported for human liver. The physiological significance of this mechanism was demonstrated by the observation that testosterone inhibited several prototypical P-450 enzyme activities, such as bufuralol 1'-hydroxylase, coumarin 7-hydroxylase, and 7-ethoxyresorufin O-dealkylase, in human liver microsomes, but not if tested against a panel of bacterial membranes containing the human P-450 isozymes that mainly catalyze these reactions. (+info)Metabolic studies using recombinant escherichia coli cells producing rat mitochondrial CYP24 CYP24 can convert 1alpha,25-dihydroxyvitamin D3 to calcitroic acid. (7/1365)
Previously we expressed rat 25-hydroxyvitamin D3 24-hydroxylase (CYP24) cDNA in Escherichia coli JM109 and showed that CYP24 catalyses three-step monooxygenation towards 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 [Akiyoshi-Shibata, M., Sakaki, T., Ohyama, Y., Noshiro, M., Okuda, K. & Yabusaki, Y. (1994) Eur. J. Biochem. 224, 335-343]. In this study, we demonstrate further oxidation by CYP24 including four- and six-step monooxygenation towards 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3, respectively. When the substrate 25-hydroxyvitamin D3 was added to a culture of recombinant E. coli, four metabolites, 24, 25-dihydroxyvitamin D3, 24-oxo-25-hydroxyvitamin D3, 24-oxo-23, 25-dihydroxyvitamin D3 and 24,25,26,27-tetranor-23-hydroxyvitamin D3 were observed. These results indicate that CYP24 catalyses at least four-step monooxygenation toward 25-hydroxyvitamin D3. Furthermore, in-vivo and in-vitro metabolic studies on 1alpha,25-dihydroxyvitamin D3 clearly indicated that CYP24 catalyses six-step monooxygenation to convert 1alpha,25-dihydroxyvitamin D3 into calcitroic acid which is known as a final metabolite of 1alpha,25-dihydroxyvitamin D3 for excretion in bile. These results strongly suggest that CYP24 is largely responsible for the metabolism of both 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3. (+info)Thyroid hormone suppresses hepatic sterol 12alpha-hydroxylase (CYP8B1) activity and messenger ribonucleic acid in rat liver: failure to define known thyroid hormone response elements in the gene. (8/1365)
Sterol 12alpha-hydroxylase (CYP 8B1) is a microsomal cytochrome P450 enzyme involved in bile acid synthesis that is of critical importance for the composition of bile acids formed in the liver. Thyroidectomy of rats caused a more than twofold increase of CYP8B1 and an almost fourfold increase of the corresponding mRNA levels compared to sham-operated rats. Treatment of intact rats with thyroxine caused a 60% reduction of enzyme activity and a 50% reduction of mRNA levels compared to rats injected with saline only. To investigate whether the promoter of the gene contains thyroid hormone response elements, the complete structure of the rat gene was defined. In similarity with the corresponding gene in mouse, rabbit and man, the rat gene was found to lack introns. It had an open reading frame containing 1500 bp corresponding to a protein of 499 amino acid residues. Although thyroid hormone decreased CYP8B1 activity and mRNA in vivo, no hitherto described thyroid hormone response elements were identified 1883 bases upstream of the transcription start site. It is concluded that rat CYP8B1 is regulated by thyroid hormone at the mRNA level. The results are discussed in relation to the structure of the gene coding for the enzyme. (+info)Fluorinated steroids are a type of synthetic corticosteroid that contain fluorine atoms in their chemical structure. Corticosteroids are a class of hormones that are naturally produced by the adrenal gland and have various important functions in the body, including regulating metabolism, immune response, and stress response.
Fluorinated steroids are often used as medications to reduce inflammation and suppress the immune system. They are commonly prescribed for a variety of conditions such as asthma, allergies, skin conditions, and autoimmune disorders. The fluorine atoms in these drugs help to prolong their activity in the body, making them more potent and longer-lasting than non-fluorinated steroids.
However, fluorinated steroids can also have significant side effects, particularly when used at high doses or for long periods of time. These may include weight gain, mood changes, thinning of the bones (osteoporosis), and increased risk of infections. Therefore, they are usually prescribed at the lowest effective dose and for the shortest duration possible to minimize these risks.
Chlorinated steroids are a type of synthetic steroid hormones that have been chemically modified to contain chlorine atoms. This alteration is often done to enhance the stability and potency of the steroid molecule. These compounds are used in various medical treatments, including as anti-inflammatory agents and for hormone replacement therapies. However, it's important to note that misuse or abuse of chlorinated steroids can lead to serious health consequences, including liver damage, cardiovascular problems, and psychiatric disorders.
Steroid hydroxylases are enzymes that catalyze the addition of a hydroxyl group (-OH) to a steroid molecule. These enzymes are located in the endoplasmic reticulum and play a crucial role in the biosynthesis of various steroid hormones, such as cortisol, aldosterone, and sex hormones. The hydroxylation reaction catalyzed by these enzymes increases the polarity and solubility of steroids, allowing them to be further metabolized and excreted from the body.
The most well-known steroid hydroxylases are part of the cytochrome P450 family, specifically CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, and CYP21A2. Each enzyme has a specific function in steroid biosynthesis, such as converting cholesterol to pregnenolone (CYP11A1), hydroxylating the 11-beta position of steroids (CYP11B1 and CYP11B2), or performing multiple hydroxylation reactions in the synthesis of sex hormones (CYP17A1, CYP19A1, and CYP21A2).
Defects in these enzymes can lead to various genetic disorders, such as congenital adrenal hyperplasia, which is characterized by impaired steroid hormone biosynthesis.
Brominated steroids are a class of compounds that are derived from natural or synthetic steroid hormones and have been chemically modified to contain bromine atoms. Steroids are a type of organic compound with a specific structure that includes four fused rings, typically composed of carbon and hydrogen atoms. In the case of brominated steroids, bromine atoms replace some of the hydrogen atoms in the steroid molecule.
Bromination of steroids is a process that can alter their biological activity and pharmacological properties. These compounds have been studied for various medical applications, including as anti-inflammatory agents, anticancer drugs, and contraceptives. However, it's important to note that brominated steroids may also have potential risks and side effects, and their use in clinical settings is subject to regulatory approval and medical supervision.
Steroids, also known as corticosteroids, are a type of hormone that the adrenal gland produces in your body. They have many functions, such as controlling the balance of salt and water in your body and helping to reduce inflammation. Steroids can also be synthetically produced and used as medications to treat a variety of conditions, including allergies, asthma, skin conditions, and autoimmune disorders.
Steroid medications are available in various forms, such as oral pills, injections, creams, and inhalers. They work by mimicking the effects of natural hormones produced by your body, reducing inflammation and suppressing the immune system's response to prevent or reduce symptoms. However, long-term use of steroids can have significant side effects, including weight gain, high blood pressure, osteoporosis, and increased risk of infections.
It is important to note that anabolic steroids are a different class of drugs that are sometimes abused for their muscle-building properties. These steroids are synthetic versions of the male hormone testosterone and can have serious health consequences when taken in large doses or without medical supervision.
Procollagen-proline dioxygenase is an enzyme that belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as an acceptor. This enzyme is involved in the post-translational modification of procollagens, which are the precursors of collagen, a crucial protein found in connective tissues such as tendons, ligaments, and skin.
Procollagen-proline dioxygenase catalyzes the reaction that adds two hydroxyl groups to specific proline residues in the procollagen molecule, converting them into hydroxyprolines. This modification is essential for the proper folding and stabilization of the collagen triple helix structure, which provides strength and resilience to connective tissues.
The enzyme requires iron as a cofactor and molecular oxygen as a substrate, with vitamin C (ascorbic acid) acting as an essential cofactor in the reaction cycle. The proper functioning of procollagen-proline dioxygenase is critical for maintaining the integrity and health of connective tissues, and deficiencies or mutations in this enzyme can lead to various connective tissue disorders, such as scurvy (caused by vitamin C deficiency) or certain forms of osteogenesis imperfecta (a genetic disorder characterized by fragile bones).
Mixed Function Oxygenases (MFOs) are a type of enzyme that catalyze the addition of one atom each from molecular oxygen (O2) to a substrate, while reducing the other oxygen atom to water. These enzymes play a crucial role in the metabolism of various endogenous and exogenous compounds, including drugs, carcinogens, and environmental pollutants.
MFOs are primarily located in the endoplasmic reticulum of cells and consist of two subunits: a flavoprotein component that contains FAD or FMN as a cofactor, and an iron-containing heme protein. The most well-known example of MFO is cytochrome P450, which is involved in the oxidation of xenobiotics and endogenous compounds such as steroids, fatty acids, and vitamins.
MFOs can catalyze a variety of reactions, including hydroxylation, epoxidation, dealkylation, and deamination, among others. These reactions often lead to the activation or detoxification of xenobiotics, making MFOs an important component of the body's defense system against foreign substances. However, in some cases, these reactions can also produce reactive intermediates that may cause toxicity or contribute to the development of diseases such as cancer.
Prolyl hydroxylases are a group of enzymes that play a crucial role in the regulation of collagen synthesis and stability. These enzymes catalyze the hydroxylation of specific proline residues in the collagen molecule, which is an essential step for the formation of stable collagen triple helices. Prolyl hydroxylases require molecular oxygen, iron, and α-ketoglutarate as cofactors to carry out this reaction. In humans, there are four known prolyl hydroxylase isoforms (PHD1, PHD2, PHD3, and SMHL), which have distinct but overlapping substrate specificities and tissue distributions. Mutations in the genes encoding these enzymes can lead to various connective tissue disorders, such as osteogenesis imperfecta and Ehlers-Danlos syndrome. Additionally, prolyl hydroxylases have been identified as key regulators of hypoxia-inducible factor (HIF) stability, making them important players in the cellular response to low oxygen levels (hypoxia).
Hypoxia-Inducible Factor (HIF) is a transcription factor that plays a crucial role in the body's response to low oxygen levels (hypoxia). HIF is composed of two subunits: an alpha subunit and a beta subunit. Under normal oxygen conditions, the alpha subunit is constantly being broken down by prolyl hydroxylase domain-containing proteins, which are a type of enzyme known as HIF-Proline Dioxygenases (HIF-PDOs).
HIF-PDOs post-translationally modify the HIF alpha subunit by adding a hydroxyl group to specific proline residues. This modification marks the HIF alpha subunit for degradation by the proteasome, a complex that breaks down unneeded or damaged proteins in the cell. However, under hypoxic conditions, the activity of HIF-PDOs is inhibited, leading to the stabilization and accumulation of HIF alpha subunits.
Once stabilized, HIF alpha subunits dimerize with HIF beta subunits and translocate to the nucleus where they bind to hypoxia response elements (HREs) in the DNA. This binding induces the expression of genes involved in various cellular responses to hypoxia, such as angiogenesis, metabolic reprogramming, and erythropoiesis. Therefore, HIF-PDOs play a critical role in regulating the body's response to low oxygen levels by controlling the stability and activity of HIF.
Hydroxylation is a biochemical process that involves the addition of a hydroxyl group (-OH) to a molecule, typically a steroid or xenobiotic compound. This process is primarily catalyzed by enzymes called hydroxylases, which are found in various tissues throughout the body.
In the context of medicine and biochemistry, hydroxylation can have several important functions:
1. Drug metabolism: Hydroxylation is a common way that the liver metabolizes drugs and other xenobiotic compounds. By adding a hydroxyl group to a drug molecule, it becomes more polar and water-soluble, which facilitates its excretion from the body.
2. Steroid hormone biosynthesis: Hydroxylation is an essential step in the biosynthesis of many steroid hormones, including cortisol, aldosterone, and the sex hormones estrogen and testosterone. These hormones are synthesized from cholesterol through a series of enzymatic reactions that involve hydroxylation at various steps.
3. Vitamin D activation: Hydroxylation is also necessary for the activation of vitamin D in the body. In order to become biologically active, vitamin D must undergo two successive hydroxylations, first in the liver and then in the kidneys.
4. Toxin degradation: Some toxic compounds can be rendered less harmful through hydroxylation. For example, phenol, a toxic compound found in cigarette smoke and some industrial chemicals, can be converted to a less toxic form through hydroxylation by enzymes in the liver.
Overall, hydroxylation is an important biochemical process that plays a critical role in various physiological functions, including drug metabolism, hormone biosynthesis, and toxin degradation.
Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the body's response to low oxygen levels, also known as hypoxia. HIF-1 is a heterodimeric protein composed of two subunits: an alpha subunit (HIF-1α) and a beta subunit (HIF-1β).
The alpha subunit, HIF-1α, is the regulatory subunit that is subject to oxygen-dependent degradation. Under normal oxygen conditions (normoxia), HIF-1α is constantly produced in the cell but is rapidly degraded by proteasomes due to hydroxylation of specific proline residues by prolyl hydroxylase domain-containing proteins (PHDs). This hydroxylation reaction requires oxygen as a substrate, and under hypoxic conditions, the activity of PHDs is inhibited, leading to the stabilization and accumulation of HIF-1α.
Once stabilized, HIF-1α translocates to the nucleus, where it heterodimerizes with HIF-1β and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes. This binding results in the activation of gene transcription programs that promote cellular adaptation to low oxygen levels. These adaptive responses include increased erythropoiesis, angiogenesis, glucose metabolism, and pH regulation, among others.
Therefore, HIF-1α is a critical regulator of the body's response to hypoxia, and its dysregulation has been implicated in various pathological conditions, including cancer, cardiovascular disease, and neurodegenerative disorders.
Alpha-ketoglutaric acid, also known as 2-oxoglutarate, is not an acid in the traditional sense but is instead a key molecule in the Krebs cycle (citric acid cycle), which is a central metabolic pathway involved in cellular respiration. Alpha-ketoglutaric acid is a crucial intermediate in the process of converting carbohydrates, fats, and proteins into energy through oxidation. It plays a vital role in amino acid synthesis and the breakdown of certain amino acids. Additionally, it serves as an essential cofactor for various enzymes involved in numerous biochemical reactions within the body. Any medical conditions or disorders related to alpha-ketoglutaric acid would typically be linked to metabolic dysfunctions or genetic defects affecting the Krebs cycle.
Alkane 1-monooxygenase is an enzyme that catalyzes the addition of one oxygen atom from molecular oxygen to a alkane, resulting in the formation of an alcohol. This reaction also requires the cofactor NADH or NADPH and generates water as a byproduct.
The general reaction catalyzed by alkane 1-monooxygenase can be represented as follows:
R-CH3 + O2 + NAD(P)H + H+ -> R-CH2OH + H2O + NAD(P)+
where R represents an alkyl group.
This enzyme is found in various microorganisms, such as bacteria and fungi, and plays a crucial role in their ability to degrade hydrocarbons, including alkanes, which are major components of fossil fuels. Alkane 1-monooxygenase has potential applications in bioremediation and the production of biofuels from renewable resources.
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase is an enzyme that plays a crucial role in the biosynthesis of collagen. The medical definition of this enzyme is:
"An enzyme that catalyzes the post-translational modification of specific lysine residues in procollagens and related proteins. This enzyme requires Fe2+, 2-oxoglutarate, molecular oxygen, and ascorbic acid as cofactors. It hydroxylates certain lysine residues to form hydroxylysine, which is essential for the stabilization of collagen triple helices and for the formation of covalent cross-links between individual collagen molecules. Mutations in this gene have been associated with several types of Ehlers-Danlos syndrome."
The systematic name for this enzyme is "procollagen-lysine, 2-oxoglutarate 5-dioxygenase (hydroxylating)." It is also known as "procollagen-lysine, lysine hydroxylase," or simply "LH." This enzyme is responsible for the hydroxylation of specific lysine residues in procollagens and related proteins during their biosynthesis. The hydroxylation reaction catalyzed by this enzyme involves the incorporation of a hydroxyl group (-OH) into the lysine side chain, resulting in the formation of hydroxylysine. This modification is essential for the proper folding and stabilization of collagen molecules, as well as for their subsequent cross-linking and assembly into extracellular matrix structures.
Defects or mutations in the gene encoding this enzyme can lead to various types of Ehlers-Danlos syndrome (EDS), a group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility.
Aldehyde oxidase is an enzyme found in the liver and other organs that helps to metabolize (break down) various substances, including drugs, alcohol, and environmental toxins. It does this by catalyzing the oxidation of aldehydes, which are organic compounds containing a functional group consisting of a carbon atom bonded to a hydrogen atom and a double bond to an oxygen atom. Aldehyde oxidase is a member of the molybdenum-containing oxidoreductase family, which also includes xanthine oxidase and sulfite oxidase. These enzymes all contain a molybdenum cofactor that plays a critical role in their catalytic activity.
Aldehyde oxidase is an important enzyme in the metabolism of many drugs, as it can convert them into more water-soluble compounds that can be easily excreted from the body. However, variations in the activity of this enzyme between individuals can lead to differences in drug metabolism and response. Some people may have higher or lower levels of aldehyde oxidase activity, which can affect how quickly they metabolize certain drugs and whether they experience adverse effects.
In addition to its role in drug metabolism, aldehyde oxidase has been implicated in the development of various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. For example, elevated levels of aldehydes produced by lipid peroxidation have been linked to oxidative stress and inflammation, which can contribute to the progression of these conditions. Aldehyde oxidase may also play a role in the detoxification of environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs), which have been associated with an increased risk of cancer.
Overall, aldehyde oxidase is an important enzyme that plays a critical role in the metabolism of drugs and other substances, as well as in the development of various diseases. Understanding its activity and regulation may help to develop new strategies for treating or preventing these conditions.
Gonadal steroid hormones, also known as gonadal sex steroids, are hormones that are produced and released by the gonads (i.e., ovaries in women and testes in men). These hormones play a critical role in the development and maintenance of secondary sexual characteristics, reproductive function, and overall health.
The three main classes of gonadal steroid hormones are:
1. Androgens: These are male sex hormones that are primarily produced by the testes but also produced in smaller amounts by the ovaries and adrenal glands. The most well-known androgen is testosterone, which plays a key role in the development of male secondary sexual characteristics such as facial hair, deepening of the voice, and increased muscle mass.
2. Estrogens: These are female sex hormones that are primarily produced by the ovaries but also produced in smaller amounts by the adrenal glands. The most well-known estrogen is estradiol, which plays a key role in the development of female secondary sexual characteristics such as breast development and the menstrual cycle.
3. Progestogens: These are hormones that are produced by the ovaries during the second half of the menstrual cycle and play a key role in preparing the uterus for pregnancy. The most well-known progestogen is progesterone, which also plays a role in maintaining pregnancy and regulating the menstrual cycle.
Gonadal steroid hormones can have significant effects on various physiological processes, including bone density, cognitive function, mood, and sexual behavior. Disorders of gonadal steroid hormone production or action can lead to a range of health problems, including infertility, osteoporosis, and sexual dysfunction.
Dioxygenases are a class of enzymes that catalyze the incorporation of both atoms of molecular oxygen (O2) into their substrates. They are classified based on the type of reaction they catalyze and the number of iron atoms in their active site. The two main types of dioxygenases are:
1. Intradiol dioxygenases: These enzymes cleave an aromatic ring by inserting both atoms of O2 into a single bond between two carbon atoms, leading to the formation of an unsaturated diol (catechol) intermediate and the release of CO2. They contain a non-heme iron(III) center in their active site.
An example of intradiol dioxygenase is catechol 1,2-dioxygenase, which catalyzes the conversion of catechol to muconic acid.
2. Extradiol dioxygenases: These enzymes cleave an aromatic ring by inserting one atom of O2 at a position adjacent to the hydroxyl group and the other atom at a more distant position, leading to the formation of an unsaturated lactone or cyclic ether intermediate. They contain a non-heme iron(II) center in their active site.
An example of extradiol dioxygenase is homogentisate 1,2-dioxygenase, which catalyzes the conversion of homogentisate to maleylacetoacetate in the tyrosine degradation pathway.
Dioxygenases play important roles in various biological processes, including the metabolism of aromatic compounds, the biosynthesis of hormones and signaling molecules, and the detoxification of xenobiotics.
Steroid receptors are a type of nuclear receptor protein that are activated by the binding of steroid hormones or related molecules. These receptors play crucial roles in various physiological processes, including development, homeostasis, and metabolism. Steroid receptors function as transcription factors, regulating gene expression when activated by their respective ligands.
There are several subtypes of steroid receptors, classified based on the specific steroid hormones they bind to:
1. Glucocorticoid receptor (GR): Binds to glucocorticoids, which regulate metabolism, immune response, and stress response.
2. Mineralocorticoid receptor (MR): Binds to mineralocorticoids, which regulate electrolyte and fluid balance.
3. Androgen receptor (AR): Binds to androgens, which are male sex hormones that play a role in the development and maintenance of male sexual characteristics.
4. Estrogen receptor (ER): Binds to estrogens, which are female sex hormones that play a role in the development and maintenance of female sexual characteristics.
5. Progesterone receptor (PR): Binds to progesterone, which is a female sex hormone involved in the menstrual cycle and pregnancy.
6. Vitamin D receptor (VDR): Binds to vitamin D, which plays a role in calcium homeostasis and bone metabolism.
Upon ligand binding, steroid receptors undergo conformational changes that allow them to dimerize, interact with co-regulatory proteins, and bind to specific DNA sequences called hormone response elements (HREs) in the promoter regions of target genes. This interaction leads to the recruitment of transcriptional machinery, ultimately resulting in the modulation of gene expression. Dysregulation of steroid receptor signaling has been implicated in various diseases, including cancer, metabolic disorders, and inflammatory conditions.
The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.
The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.
The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.
There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:
1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.
Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.
Phenylalanine Hydroxylase (PAH) is an enzyme that plays a crucial role in the metabolism of the essential amino acid phenylalanine. This enzyme is primarily found in the liver and is responsible for converting phenylalanine into tyrosine, another amino acid. PAH requires a cofactor called tetrahydrobiopterin (BH4) to function properly.
Defects or mutations in the gene that encodes PAH can lead to a genetic disorder known as Phenylketonuria (PKU). In PKU, the activity of PAH is significantly reduced or absent, causing an accumulation of phenylalanine in the body. If left untreated, this condition can result in severe neurological damage and intellectual disability due to the toxic effects of high phenylalanine levels on the developing brain. A strict low-phenylalanine diet and regular monitoring of blood phenylalanine levels are essential for managing PKU and preventing associated complications.
Cholestanetriol 26-monooxygenase is an enzyme that is involved in the metabolism of bile acids and steroids in the body. This enzyme is responsible for adding a hydroxyl group (-OH) to the cholestanetriol molecule at position 26, which is a critical step in the conversion of cholestanetriol to bile acids.
The gene that encodes this enzyme is called CYP3A4, which is located on chromosome 7 in humans. Mutations in this gene can lead to various metabolic disorders, including impaired bile acid synthesis and altered steroid hormone metabolism.
Deficiency or dysfunction of cholestanetriol 26-monooxygenase has been associated with several diseases, such as liver disease, cerebrotendinous xanthomatosis, and some forms of cancer. Therefore, understanding the function and regulation of this enzyme is essential for developing new therapies and treatments for these conditions.
Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the cellular response to low oxygen levels, also known as hypoxia. It is a heterodimeric protein composed of two subunits: HIF-1α and HIF-1β.
Under normoxic conditions (adequate oxygen supply), HIF-1α is constantly produced but rapidly degraded by proteasomes due to the action of prolyl hydroxylases, which mark it for destruction in the presence of oxygen. However, under hypoxic conditions, the activity of prolyl hydroxylases is inhibited, leading to the stabilization and accumulation of HIF-1α.
Once stabilized, HIF-1α translocates to the nucleus and forms a complex with HIF-1β. This complex then binds to hypoxia-responsive elements (HREs) in the promoter regions of various genes involved in angiogenesis, glucose metabolism, erythropoiesis, cell survival, and other processes that help cells adapt to low oxygen levels.
By activating these target genes, HIF-1 plays a critical role in regulating the body's response to hypoxia, including promoting the formation of new blood vessels (angiogenesis), enhancing anaerobic metabolism, and inhibiting cell proliferation and apoptosis under low oxygen conditions. Dysregulation of HIF-1 has been implicated in several diseases, such as cancer, cardiovascular disease, and ischemic disorders.
Tryptophan hydroxylase is an enzyme that plays a crucial role in the synthesis of neurotransmitters and hormones, including serotonin and melatonin. It catalyzes the conversion of the essential amino acid tryptophan to 5-hydroxytryptophan (5-HTP), which is then further converted to serotonin. This enzyme exists in two isoforms, TPH1 and TPH2, with TPH1 primarily located in peripheral tissues and TPH2 mainly found in the brain. The regulation of tryptophan hydroxylase activity has significant implications for mood, appetite, sleep, and pain perception.
Xanthine dehydrogenase (XDH) is an enzyme involved in the metabolism of purines, which are nitrogen-containing compounds that form part of DNA and RNA. Specifically, XDH helps to break down xanthine and hypoxanthine into uric acid, a waste product that is excreted in the urine.
XDH can exist in two interconvertible forms: a dehydrogenase form (XDH) and an oxidase form (XO). In its dehydrogenase form, XDH uses NAD+ as an electron acceptor to convert xanthine into uric acid. However, when XDH is converted to its oxidase form (XO), it can use molecular oxygen as an electron acceptor instead, producing superoxide and hydrogen peroxide as byproducts. These reactive oxygen species can contribute to oxidative stress and tissue damage in the body.
Abnormal levels or activity of XDH have been implicated in various diseases, including gout, cardiovascular disease, and neurodegenerative disorders.
I'm sorry for any confusion, but "Molybdenum" is not a medical term. It is an element with the symbol Mo and atomic number 42 on the periodic table. Molybdenum is used in various industries, including medicine, for example in the production of surgical instruments and some prosthetics due to its strength and resistance to corrosion. However, it is not a term used to describe a medical condition or bodily process. If you have any questions related to elements and their uses in medicine, I'd be happy to help with those!
"Methylococcus" is a genus of bacteria that have the ability to oxidize methane as their source of carbon and energy. These bacteria are gram-negative, non-spore forming, and facultatively aerobic, meaning they can grow in both the presence and absence of oxygen. They typically form spherical or coccoid cells and are commonly found in environments that are rich in methane, such as soil, freshwater, and marine habitats. One notable species is "Methylococcus capsulatus," which has been studied for its potential use in bioremediation and biofuel production.
Dicarboxylic amino acids are a type of amino acid that contain two carboxyl (–COOH) groups in their chemical structure. In the context of biochemistry and human physiology, the dicarboxylic amino acids include aspartic acid (Asp) and glutamic acid (Glu). These amino acids play important roles in various biological processes, such as neurotransmission, energy metabolism, and cell signaling.
Aspartic acid (Asp, D) is an alpha-amino acid with the chemical formula: HO2CCH(NH2)CH2CO2H. It is a genetically encoded amino acid, which means that it is coded for by DNA in the genetic code and is incorporated into proteins during translation. Aspartic acid has a role as a neurotransmitter in the brain, where it is involved in excitatory neurotransmission.
Glutamic acid (Glu, E) is another alpha-amino acid with the chemical formula: HO2CCH(NH2)CH2CH2CO2H. Like aspartic acid, glutamic acid is a genetically encoded amino acid and is an important component of proteins. Glutamic acid also functions as a neurotransmitter in the brain, where it is the primary mediator of excitatory neurotransmission. Additionally, glutamic acid can be converted into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) through the action of the enzyme glutamate decarboxylase.
Both aspartic acid and glutamic acid are considered to be non-essential amino acids, meaning that they can be synthesized by the human body and do not need to be obtained through the diet. However, it is important to note that a balanced and nutritious diet is necessary for maintaining optimal health and supporting the body's ability to synthesize these and other amino acids.
The Von Hippel-Lindau (VHL) tumor suppressor protein is a crucial component in the regulation of cellular growth and division, specifically through its role in oxygen sensing and the ubiquitination of hypoxia-inducible factors (HIFs). The VHL protein forms part of an E3 ubiquitin ligase complex that targets HIFs for degradation under normoxic conditions. In the absence of functional VHL protein or in hypoxic environments, HIFs accumulate and induce the transcription of genes involved in angiogenesis, cell proliferation, and metabolism.
Mutations in the VHL gene can lead to the development of Von Hippel-Lindau syndrome, a rare inherited disorder characterized by the growth of tumors and cysts in various organs, including the central nervous system, retina, kidneys, adrenal glands, and pancreas. These tumors often arise from the overactivation of HIF-mediated signaling pathways due to the absence or dysfunction of VHL protein.
Oxygen is a colorless, odorless, tasteless gas that constitutes about 21% of the earth's atmosphere. It is a crucial element for human and most living organisms as it is vital for respiration. Inhaled oxygen enters the lungs and binds to hemoglobin in red blood cells, which carries it to tissues throughout the body where it is used to convert nutrients into energy and carbon dioxide, a waste product that is exhaled.
Medically, supplemental oxygen therapy may be provided to patients with conditions such as chronic obstructive pulmonary disease (COPD), pneumonia, heart failure, or other medical conditions that impair the body's ability to extract sufficient oxygen from the air. Oxygen can be administered through various devices, including nasal cannulas, face masks, and ventilators.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
Cell hypoxia, also known as cellular hypoxia or tissue hypoxia, refers to a condition in which the cells or tissues in the body do not receive an adequate supply of oxygen. Oxygen is essential for the production of energy in the form of ATP (adenosine triphosphate) through a process called oxidative phosphorylation. When the cells are deprived of oxygen, they switch to anaerobic metabolism, which produces lactic acid as a byproduct and can lead to acidosis.
Cell hypoxia can result from various conditions, including:
1. Low oxygen levels in the blood (hypoxemia) due to lung diseases such as chronic obstructive pulmonary disease (COPD), pneumonia, or high altitude.
2. Reduced blood flow to tissues due to cardiovascular diseases such as heart failure, peripheral artery disease, or shock.
3. Anemia, which reduces the oxygen-carrying capacity of the blood.
4. Carbon monoxide poisoning, which binds to hemoglobin and prevents it from carrying oxygen.
5. Inadequate ventilation due to trauma, drug overdose, or other causes that can lead to respiratory failure.
Cell hypoxia can cause cell damage, tissue injury, and organ dysfunction, leading to various clinical manifestations depending on the severity and duration of hypoxia. Treatment aims to correct the underlying cause and improve oxygen delivery to the tissues.
Alkanes are a group of saturated hydrocarbons, which are characterized by the presence of single bonds between carbon atoms in their molecular structure. The general formula for alkanes is CnH2n+2, where n represents the number of carbon atoms in the molecule.
The simplest and shortest alkane is methane (CH4), which contains one carbon atom and four hydrogen atoms. As the number of carbon atoms increases, the length and complexity of the alkane chain also increase. For example, ethane (C2H6) contains two carbon atoms and six hydrogen atoms, while propane (C3H8) contains three carbon atoms and eight hydrogen atoms.
Alkanes are important components of fossil fuels such as natural gas, crude oil, and coal. They are also used as starting materials in the production of various chemicals and materials, including plastics, fertilizers, and pharmaceuticals. In the medical field, alkanes may be used as anesthetics or as solvents for various medical applications.
Anoxia is a medical condition that refers to the absence or complete lack of oxygen supply in the body or a specific organ, tissue, or cell. This can lead to serious health consequences, including damage or death of cells and tissues, due to the vital role that oxygen plays in supporting cellular metabolism and energy production.
Anoxia can occur due to various reasons, such as respiratory failure, cardiac arrest, severe blood loss, carbon monoxide poisoning, or high altitude exposure. Prolonged anoxia can result in hypoxic-ischemic encephalopathy, a serious condition that can cause brain damage and long-term neurological impairments.
Medical professionals use various diagnostic tests, such as blood gas analysis, pulse oximetry, and electroencephalography (EEG), to assess oxygen levels in the body and diagnose anoxia. Treatment for anoxia typically involves addressing the underlying cause, providing supplemental oxygen, and supporting vital functions, such as breathing and circulation, to prevent further damage.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
Biopterin is a type of pteridine compound that acts as a cofactor in various biological reactions, particularly in the metabolism of amino acids such as phenylalanine and tyrosine. It plays a crucial role in the production of neurotransmitters like dopamine, serotonin, and noradrenaline. Biopterin exists in two major forms: tetrahydrobiopterin (BH4) and dihydrobiopterin (BH2). BH4 is the active form that participates in enzymatic reactions, while BH2 is an oxidized form that can be reduced back to BH4 by the action of dihydrobiopterin reductase.
Deficiencies in biopterin metabolism have been linked to several neurological disorders, including phenylketonuria (PKU), dopamine-responsive dystonia, and certain forms of autism. In these conditions, the impaired synthesis or recycling of biopterin can lead to reduced levels of neurotransmitters, causing various neurological symptoms.
Steroid 21-hydroxylase, also known as CYP21A2, is a crucial enzyme involved in the synthesis of steroid hormones in the adrenal gland. Specifically, it catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone in the glucocorticoid and mineralocorticoid pathways, respectively.
Deficiency or mutations in this enzyme can lead to a group of genetic disorders called congenital adrenal hyperplasia (CAH), which is characterized by impaired cortisol production and disrupted hormonal balance. Depending on the severity of the deficiency, CAH can result in various symptoms such as ambiguous genitalia, precocious puberty, sexual infantilism, infertility, and increased risk of adrenal crisis.
Steroid 11β-hydroxylase
Steroid hydroxylase
Adrenodoxin-NADP+ reductase
Late onset congenital adrenal hyperplasia
Maria New
Aldosterone synthase
21-Hydroxylase
Steroid 9alpha-monooxygenase
Androgen backdoor pathway
Cunninghamella elegans
Alternatives to animal testing
Rhizopus oryzae
Peter M. Schneider
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Walter L. Miller (endocrinologist)
Drug metabolism
Colin Skinner
Neurosteroidogenesis inhibitor
7α-Thiospironolactone
CYP154C3
Glucocorticoid remediable aldosteronism
Adrenal ferredoxin
Steroidogenic factor 1
Steroid 15beta-monooxygenase
CYP7B1
21-Deoxycortisol
Intersex
PITX1
Androsterone
Steroid 11β-hydroxylase - Wikipedia
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Congenital Adrenal Hyperplasia: Practice Essentials, Background, Pathophysiology
2019 AACC
Congenital adrenal hyp10
- A mutation in genes encoding 11β-hydroxylase is associated with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. (wikipedia.org)
- 11β-hydroxylase is involved in the metabolism of 17α-hydroxyprogesterone to 21-deoxycortisol, in cases of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. (wikipedia.org)
- Steroid 21-hydroxylase deficiency accounts for about 95% of cases of congenital adrenal hyperplasia (CAH). (columbia.edu)
- Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. (medlineplus.gov)
- CAH due to 11-beta-hydroxylase deficiency accounts for 5 to 8 percent of all cases of congenital adrenal hyperplasia. (medlineplus.gov)
- 21-hydroxylase deficiency is responsible for about 95 percent of all cases of congenital adrenal hyperplasia. (medlineplus.gov)
- Congenital adrenal hyperplasia (CAH) is a common genetic disorder due to defective 21-hydroxylation of steroid hormones. (elsevierpure.com)
- Knowledge of this pathway is vital to understanding the clinical presentation of 11-beta-hydroxylase deficiency and the other variants of congenital adrenal hyperplasia (CAH). (medscape.com)
- Context: Congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase deficiency in 95% of the cases. (endocrine-abstracts.org)
- Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21OHD) is the commonest inborn error in steroid biosynthesis. (endocrine-abstracts.org)
Vitamin D3 24-Hydroxylase1
- A cytochrome P450 enzyme family that includes VITAMIN D3 24-HYDROXYLASE. (bvsalud.org)
Enzyme9
- 11β-hydroxylase is a steroidogenic enzyme, i.e. the enzyme involved in the metabolism of steroids. (wikipedia.org)
- A mitochondrial cytochrome P450 enzyme that catalyzes the 11-beta-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. (childrensmercy.org)
- The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. (medlineplus.gov)
- CAH due to 11-beta-hydroxylase deficiency is caused by a shortage (deficiency) of the 11-beta-hydroxylase enzyme. (medlineplus.gov)
- The amount of functional 11-beta-hydroxylase enzyme that an individual produces typically determines the extent of abnormal sexual development. (medlineplus.gov)
- The CYP21A2 gene provides instructions for making an enzyme called 21-hydroxylase. (medlineplus.gov)
- 21-hydroxylase deficiency is caused by a shortage (deficiency) of the 21-hydroxylase enzyme. (medlineplus.gov)
- The amount of functional 21-hydroxylase enzyme determines the severity of the disorder. (medlineplus.gov)
- The activity of the enzyme 21-hydroxylase, encoded by the CYP21A2 gene, is deficient, leading to an accumulation of 17-hydroxyprogesterone (17-OHP) and subsequent elevation of androgens. (mssm.edu)
Cytochrome4
- The CYP11B1 gene encodes 11β-hydroxylase - a member of the cytochrome P450 superfamily of enzymes. (wikipedia.org)
- The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. (wikipedia.org)
- The human P450XXIA2 gene encodes cytochrome P450c21 [steroid 21-monooxygenase (steroid 21-hydroxylase), EC 1.14.99.10], which mediates 21-hydroxylation. (elsevierpure.com)
- T cell responses to steroid cytochrome P450 21‑ hydroxylase in patients with autoimmune primary adrenal insufficiency. (prolekare.cz)
Classic 21-hydroxylas2
- Approximately 75 percent of individuals with classic 21-hydroxylase deficiency have the salt-wasting type. (medlineplus.gov)
- We report a female infant aged two months, from Nag Hammadi, Upper Egypt, whose presentation and laboratory abnormalities were consistent with CAH, the classic 21-hydroxylase deficiency (salt-wasting type). (uwi.edu)
Biosynthesis2
- Bovine adrenodoxin (Adx) and adrenodoxin reductase (AdR) are involved in steroid hormone biosynthesis in the adrenal gland mitochondria. (nature.com)
- It is derived from progesterone via 17α-hydroxylase and is a chemical intermediate in the biosynthesis of several other steroids, including cortisol. (cdc.gov)
CYP21A22
- Mutations in the CYP21A2 gene cause 21-hydroxylase deficiency. (medlineplus.gov)
- It is caused by mutations in the 21-hydroxylase gene (CYP21A2). (endocrine-abstracts.org)
ACTH6
- CYP11B1 (11β-hydroxylase) is expressed at high levels and is regulated by ACTH, while CYP11B2 (aldosterone synthase) is usually expressed at low levels and is regulated by angiotensin II. (wikipedia.org)
- In the zona fasciculata, the typical end product of the steroid biosynthetic pathway is cortisol, as shown in the image above, and cortisol regulates pituitary ACTH production through negative feedback inhibition. (medscape.com)
- Loss of 11-beta-hydroxylase activity in the adrenal gland blocks the synthesis of cortisol and results in an increase in ACTH production. (medscape.com)
- CAH due to 11-hydroxylase deficiency is due to genetic defects of CYP11B1 characterized by impaired conversion of 11-deoxycortisol to cortisol, reduced cortisol, impaired conversion of DOC to corticosterone, and increased 11-deoxycortisol, DOC, and ACTH secretion. (medscape.com)
- To investigate this, we cultured HFT tissue with and without ACTH for up to 5 days, and quantified adrenal steroid hormones and expression of adrenal steroidogenic enzymes. (bvsalud.org)
- In contrast to fetal adrenal tissues, the expression of ACTH receptor MC2R was either absent or expressed at extremely low levels in ex vivo HFT tissue and no clear response to ACTH in gene expression or steroid hormone production was observed. (bvsalud.org)
Aldosterone2
- Steroidogenic pathway for cortisol, aldosterone, and sex steroid synthesis. (medscape.com)
- The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well understood. (bvsalud.org)
Metabolism3
- The rate of electron leakage during metabolism depends on the functional groups of the steroid substrate. (wikipedia.org)
- Little is known about the effects of the vitamin D receptor (VDR) on hepatic activity of human cholesterol 7α-hydroxylase (CYP7A1) and cholesterol metabolism. (nih.gov)
- Congenital abnormality of steroid metabolism (eg, adrenogenital syndrome, 17? (unboundmedicine.com)
Cholesterol3
- Cholesterol 7-alpha-Hydroxylase" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uams.edu)
- This graph shows the total number of publications written about "Cholesterol 7-alpha-Hydroxylase" by people in UAMS Profiles by year, and whether "Cholesterol 7-alpha-Hydroxylase" was a major or minor topic of these publications. (uams.edu)
- Below are the most recent publications written about "Cholesterol 7-alpha-Hydroxylase" by people in Profiles over the past ten years. (uams.edu)
Precursors2
- When 11-beta-hydroxylase is lacking, precursors that are used to form cortisol and corticosterone build up in the adrenal glands and are converted to androgens. (medlineplus.gov)
- A buildup in the precursors used to form corticosterone increases salt retention, leading to hypertension in individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency. (medlineplus.gov)
Hormones3
- In people with CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones. (medlineplus.gov)
- This data will allow for analysis of the selected steroid hormones and related binding protein that can be used to assist in disease diagnosis, treatment, and prevention of diseases, such as Polycystic Ovary Syndrome (PCOS), androgen deficiency, certain cancers, and hormone imbalances. (cdc.gov)
- While DHEAS itself is hormonally inactive, it can be converted to DHEA, which in turn can serve as a precursor to more active steroid hormones, such as testosterone or estradiol. (cdc.gov)
Biosynthetic pathway1
- The steroid biosynthetic pathway is shown in the image below. (medscape.com)
Corticosterone2
- 11β-hydroxylase has strong catalytic activity during conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone, by catalyzing the hydroxylation of carbon hydrogen bond at 11-beta position. (wikipedia.org)
- The adrenal fasciculata production of corticosterone, a weak glucocorticoid, and deoxycorticosterone (DOC), a potent mineralocorticoid, is minimal and relatively unimportant in healthy normal individuals, but it is important in patients with 11-beta-hydroxylase deficiency. (medscape.com)
Progesterone1
- Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone. (cdc.gov)
Protein2
- The product of this CYP11B1 gene is the 11β-hydroxylase protein. (wikipedia.org)
- This protein localizes to the mitochondrial inner membrane and is involved in the conversion of various steroids in the adrenal cortex. (wikipedia.org)
CYP11B14
- Humans have two isozymes with 11β-hydroxylase activity: CYP11B1 and CYP11B2. (wikipedia.org)
- The CYP11B1 isozyme has strong 11β-hydroxylase activity, but the activity of 18-hydroxylase is only one-tenth of CYP11B2. (wikipedia.org)
- The weak 18-hydroxylase activity of CYP11B1 explains why an adrenal with suppressed CYP11B2 expression continues to synthesize 18-hydroxycorticosterone. (wikipedia.org)
- Mutations in the CYP11B1 gene cause CAH due to 11-beta-hydroxylase deficiency. (medlineplus.gov)
Genes1
- And disadvantages of taking Stanozolol it just means you transcriptional regulation of the genes encoding P-450 steroid hydroxylases. (mdtmag.com)
Mutations2
- Introduction: Steroid 5-α reductase type 2 deficiency causes 46,XY disorder of sex development (DSD) and is an autosomal recessive disorder resulting from mutations in the SRD5A2 gene. (endocrine-abstracts.org)
- Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A , is the most common form of CAH, accounting for more than 90% of cases. (medscape.com)
MICROSOMES2
Androgen3
- Patients with 11-beta-hydroxylase deficiency present with features of androgen excess, including masculinization of female newborns and precocious puberty in male children. (medscape.com)
- Patients with 11-beta-hydroxylase deficiency have clinical features of androgen excess, such as premature sexual maturation observed in boys and virilization in females. (medscape.com)
- These symptoms are the result of excess adrenal androgen production and are similar to those observed in the more common virilizing form of CAH, 21-hydroxylase deficiency. (medscape.com)
Antibodies1
- The KRONUS® 21-OHAb Kit is for the qualitative determination of antibodies to 21-hydroxylase in human serum. (jspargo.com)
Genetic3
- The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases and can have diverse manifestations: from the salt wasting to the non-classical form due to a highly variable genetic mutation. (uwi.edu)
- Hormonal testing is important in making the diagnosis of 21-hydroxylase deficiency, yet genetic testing is crucial to secure the diagnosis. (mssm.edu)
- In Genetic Steroid Disorders (pp. 29-51). (mssm.edu)
Defect1
- An enzymatic defect in 11-beta-hydroxylase is the second most common variant of CAH and accounts for approximately 5-8% of cases. (medscape.com)
Autoantibody1
- Autoantibody epitope mapping of the 21‑ hydroxylase antigen in autoimmune Addison's disease. (prolekare.cz)
Isoenzymes1
- Humans have two 11-beta-hydroxylase isoenzymes that are 93% identical. (medscape.com)
Diagnosis1
- The measurement of steroid 21-OHAbs is useful as an aid in the diagnosis of autoimmune adrenal disease, whether expressed as autoimmune Addison's disease (isolated) or Addison's disease as part of the more complex autoimmune polyglandular syndrome (APS), type I or II, and may also aid in the detection of those at risk of developing autoimmune adrenal failure in the future. (jspargo.com)
Nonclassic1
- Nonclassic 11-beta-hydroxylase deficiency is more subtle and presents later in life. (medscape.com)
Zona fasciculata1
- Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. (wikipedia.org)
Benzphetamine1
- Cd and Zn caused concentration dependent decreases in benzphetamine- demethylase and biphenyl-hydroxylase activities in liver, lung, and adrenals. (cdc.gov)
Androgens2
- The excess production of androgens leads to abnormalities of sexual development, particularly in females with CAH due to 11-beta-hydroxylase deficiency. (medlineplus.gov)
- The excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency. (medlineplus.gov)
Dehydroepiandrosterone1
- It is a conjugated steroid converted by the sulfation of dehydroepiandrosterone (DHEA) at the 3β position via hydroxysteroid sulfotransferase. (cdc.gov)
Profiles2
- Below are the most recent publications written about "Steroid 11-beta-Hydroxylase" by people in Profiles. (childrensmercy.org)
- When the lipid profiles and glucose administered as a supplement steroid use by athletes vary markedly to those used in clinical studies. (mdtmag.com)
Activity1
- In addition to the 11β-hydroxylase activity, both isozymes have 18-hydroxylase activity. (wikipedia.org)
Hormone production1
- 21-hydroxylase deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development. (medlineplus.gov)
Males1
- Males and females with either classic form of 21-hydroxylase deficiency tend to have an early growth spurt, but their final adult height is usually shorter than others in their family. (medlineplus.gov)