Vitamin B 12
Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene. (1/91)We previously showed that rat liver betaine-homocysteine methyltransferase (BHMT) mRNA content and activity increased 4-fold when rats were fed a methionine-deficient diet containing adequate choline, compared with rats fed the same diet with control levels of methionine (Park, E. I., Renduchintala, M. S., and Garrow, T. A. (1997) J. Nutr. Biochem. 8, 541-545). A further 2-fold increase was observed in rats fed the methionine-deficient diet with supplemental betaine. The nutrition studies reported here were designed to determine whether other methyl donors would induce rat liver BHMT gene expression when added to a methionine-deficient diet and to define the relationship between the degree of methionine restriction and level of methyl donor intake on BHMT expression. Therefore, rats were fed amino acid-defined diets varying in methionine and methyl donor composition. The effect of diet on BHMT expression was evaluated using Northern, Western, and enzyme activity analyses. Similar to when betaine was added to a methionine-deficient diet, choline or sulfonium analogs of betaine induced BHMT expression. The diet-induced induction of hepatic BHMT activity was mediated by increases in the steady-state level of its mRNA and immunodetectable protein. Using methyl donor-free diets, we found that methionine restriction was required but alone not sufficient for the high induction of BHMT expression. Concomitant with methionine restriction, dietary methyl groups were required for high levels of BHMT induction, and a dose-dependent relationship was observed between methyl donor intake and BHMT induction. Furthermore, the severity of methionine restriction influenced the magnitude of BHMT induction. To study the molecular mechanisms that regulate the expression of BHMT, we have cloned the human BHMT gene. This gene spans about 20 kilobases of DNA and contains 8 exons and 7 introns. Using RNA isolated from human liver and hepatoma cells, a major transcriptional start site has been mapped using the 5' rapid amplification of cDNA ends technique, and this start site is 26 nucleotides downstream from a putative TATA box. (+info)
Autolysosomal membrane-associated betaine homocysteine methyltransferase. Limited degradation fragment of a sequestered cytosolic enzyme monitoring autophagy. (2/91)We compared the membrane proteins of autolysosomes isolated from leupeptin-administered rat liver with those of lysosomes. In addition to many polypeptides common to the two membranes, the autolysosomal membranes were found to be more enriched in endoplasmic reticulum lumenal proteins (protein-disulfide isomerase, calreticulin, ER60, BiP) and endosome/Golgi markers (cation-independent mannose 6-phosphate receptor, transferrin receptor, Golgi 58-kDa protein) than lysosomal membranes. The autolysosomal membrane proteins include three polypeptides (44, 35, and 32 kDa) whose amino-terminal sequences have not yet been reported. Combining immunoblotting and reverse transcriptase-polymerase chain reaction analyses, we identified the 44-kDa peptide as the intact subunit of betaine homocysteine methyltransferase and the 35- and 32-kDa peptides as two proteolytic fragments. Pronase digestion of autolysosomes revealed that the 44-kDa and 32-kDa peptides are present in the lumen, whereas the 35-kDa peptide is not. In primary hepatocyte cultures, the starvation-induced accumulation of the 32-kDa peptide occurs in the presence of E64d, showing that the 32-kDa peptide is formed from the sequestered 44-kDa peptide during autophagy. The accumulation is induced by rapamycin but completely inhibited by wortmannin, 3-methyladenine, and bafilomycin. Thus, detection of the 32-kDa peptide by immunoblotting can be used as a streamlined assay for monitoring autophagy. (+info)
Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase. (3/91)The cDNA encoding rat betaine-homocysteine S-methyltransferase (BHMT) was isolated through production of monoclonal antibodies against protein fractions enriched with apolipoprotein B (apo B)-mRNA-editing complexes. BHMT mRNA was expressed predominantly in liver, and also in kidney, but not in small intestine. In stable McArdle RH-7777 (McA) cell lines expressing differing levels of BHMT, the editing efficiency of apo B mRNA was unchanged. Evaluation of apo B-mRNA expression revealed that steady-state levels were increased significantly and in parallel with BHMT protein expression. The highest levels of BHMT mRNA and BHMT enzyme activity expressed in stably transfected McA cells were comparable with those found in rat hepatocytes. In contrast to the changes in apo B-mRNA abundance, levels of other apolipoprotein-encoding mRNAs and several liver-specific and ubiquitously expressed mRNAs were unchanged by BHMT expression. In the cell line expressing the highest level of BHMT, apo B-containing lipoprotein secretion was increased, indicating utilization of increased endogenous message. Results suggest that apo B-mRNA abundance in McA cells is related to the expression of BHMT, an enzyme important in homocysteine metabolism. (+info)
Leupeptin-induced appearance of partial fragment of betaine homocysteine methyltransferase during autophagic maturation in rat hepatocytes. (4/91)A cytosolic enzyme, betaine homocysteine methyltransferase (BHMT), and its partial fragments were discovered as autolysosomal membrane proteins from rat liver in the presence of leupeptin [Ueno et al. (1999) J. Biol. Chem. 274, 15222-15229]. The present study was undertaken to further characterize the transport and processing of BHMT from cytosol to autolysosome and to test if the fragment can be used as an in vitro probe for the maturation step of macroautophagy. Upon subcellular fractionation, BHMT (p44) was found in all fractions, while its 32-kDa fragment (p32) was found only in the mitochondrial-lysosomal (ML) fraction. Incubation of isolated hepatocytes with leupeptin induced time-dependent accumulation of p32 in the ML fraction from 30 to 90 min after the start of incubation. However, chloroquine completely inhibited the appearance of p32, indicating that the processing from p44 to p32 is lysosomal. Incubation with Bafilomycin A(1), a vacuolar H(+)-ATPase inhibitor, together with leupeptin, led to linear accumulation of p44, but not of p32. The p44 accumulation rate was calculated to be 4.9%/h, which was comparable to autophagic sequestration rate. The distribution of p44 within the ML fraction turned out to be dual, i.e., the membrane-surface attached and luminal/sedimentable forms. Amino acids and 3-methyladenine, both of which specifically suppress macroautophagy, inhibited the accumulation of p32 as well as of p44. Finally, energy-dependent appearance of p32 was demonstrated during incubation of postnucler supernatant fractions, making it possible to establish an in vitro assay system. All the results strongly support the idea that BHMT is taken up and degraded to p32 through the macroautophagic pathway, and that p32 could be a novel probe for the maturation of macroautophagy. (+info)
Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. (5/91)BACKGROUND: Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity. METHODS: Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression. RESULTS: Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy. CONCLUSIONS: DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF. (+info)
Selenium deficiency in Fisher-344 rats decreases plasma and tissue homocysteine concentrations and alters plasma homocysteine and cysteine redox status. (6/91)The purpose of the present study was to determine the effect of graded amounts of dietary selenium on plasma and tissue parameters of methionine metabolism including homocysteine. Male weanling Fisher-344 rats (n = 7-8/group) were fed a selenium-deficient, torula yeast-based diet, supplemented with 0 (selenium deficient), 0.02, 0.05 or 0.1 microg (adequate) selenium (as selenite)/g diet. After 61 d, plasma total homocysteine and cysteine were decreased (P < 0.0001) and glutathione increased (P < 0.0001) by selenium deficiency. The concentrations of homocysteine in kidney and heart were decreased (P = 0.02) by selenium deficiency. The activities of liver betaine homocysteine methyltransferase, methionine synthase, S-adenosylmethionine synthase, cystathionine synthase and cystathionase were determined; selenium deficiency affected only betaine homocysteine methyltransferase, which was decreased (P < 0.0001). The ratios of plasma free reduced homocysteine (or cysteine) to free oxidized homocysteine (or cysteine) or to total homocysteine (or cysteine) were increased by selenium deficiency, suggesting that selenium status affects the normally tightly controlled redox status of these thiols. Most differences due to dietary selenium were between rats fed 0 or 0.02 microg selenium/g diet and those fed 0.05 or 0.1 microg selenium/g diet. The metabolic consequences of a marked decrease in plasma homocysteine and smaller but significant decreases in tissue homocysteine are not known. (+info)
Methionine supply to growing steers affects hepatic activities of methionine synthase and betaine-homocysteine methyltransferase, but not cystathionine synthase. (7/91)The effects of supplemental methionine (Met), supplied abomasally, on the activities of methionine synthase (MS), cystathionine synthase (CS) and betaine-homocysteine methyltransferase (BHMT) were studied in growing steers. Six Holstein steers (205 kg) were used in a replicated 3 x 3 Latin square experiment. Steers were fed 2.6 kg dry matter daily of a diet containing 83% soybean hulls and 8% wheat straw. Ruminal infusions of 180 g/d acetate, 180 g/d propionate, 45 g/d butyrate, and abomasal infusion of 300 g/d dextrose provided additional energy. An amino acid mixture (299 g/d) limiting in Met was infused into the abomasum to ensure that nonsulfur amino acids did not limit growth. Treatments were infused abomasally and included 0, 5 or 10 g/d L-Met. Retained N (20.5, 26.9 and 31.6 g/d for 0, 5 and 10 g/d L-Met, respectively) increased (P < 0.01) linearly with increased supplemental Met. Hepatic Met, vitamin B-12, S-adenosylmethionine and S-adenosylhomocysteine were not affected by Met supplementation. Hepatic folates tended (P = 0.07) to decrease linearly with Met supplementation. All three enzymes were detected in hepatic tissue of our steers. Hepatic CS activity was not affected by Met supplementation. Hepatic MS decreased (P < 0.01) linearly with increasing Met supply, and hepatic BHMT activity responded quadratically (P = 0.04), with 0 and 10 g/d Met being higher than the intermediate level. Data from this experiment indicate that sulfur amino acid metabolism may be regulated differently in cattle than in other tested species. (+info)
Betaine-homocysteine methyltransferase: zinc in a distorted barrel. (8/91)Betaine-homocysteine methyl transferase (BHMT) catalyzes the synthesis of methionine from betaine and homocysteine (Hcy), utilizing a zinc ion to activate Hcy. BHMT is a key liver enzyme that is important for homocysteine homeostasis. X-ray structures of human BHMT in its oxidized (Zn-free) and reduced (Zn-replete) forms, the latter in complex with the bisubstrate analog, S(delta-carboxybutyl)-L-homocysteine, were determined at resolutions of 2.15 A and 2.05 A. BHMT is a (beta/alpha)(8) barrel that is distorted to construct the substrate and metal binding sites. The zinc binding sequences G-V/L-N-C and G-G-C-C are at the C termini of strands beta6 and beta8. Oxidation to the Cys217-Cys299 disulfide and expulsion of Zn are accompanied by local rearrangements. The structures identify Hcy binding fingerprints and provide a prototype for the homocysteine S-methyltransferase family. (+info)
Betaine-Homocysteine S-Methyltransferase (BHMT) is an enzyme that catalyzes the methylation of homocysteine to methionine using betaine as a methyl donor. This reaction plays a crucial role in maintaining the homeostasis of methionine and homocysteine, which are important for various biological processes such as methylation reactions, protein synthesis, and neurotransmitter production.
The BHMT enzyme is primarily found in the liver and kidneys, where it helps to regulate the levels of homocysteine in the body. Elevated levels of homocysteine have been linked to several health issues, including cardiovascular disease, neurological disorders, and bone diseases. Therefore, BHMT plays an essential role in maintaining overall health by regulating homocysteine metabolism.
Glycine N-Methyltransferase (GNMT) is an enzyme that plays a crucial role in methionine and homocysteine metabolism. It is primarily found in the liver and to some extent in the kidneys, pancreas, and brain.
GNMT catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to glycine, forming S-adenosylhomocysteine (SAH) and sarcosine as products. This reaction helps regulate the levels of SAM, SAH, and homocysteine in the body.
Additionally, GNMT has been shown to have other functions, such as detoxification of xenobiotics and regulation of lipid metabolism. Abnormal GNMT activity or expression has been linked to various diseases, including liver disorders, cardiovascular disease, and cancer.
Betaine, also known as trimethylglycine, is a naturally occurring compound that can be found in various foods such as beets, spinach, and whole grains. In the body, betaine functions as an osmolyte, helping to regulate water balance in cells, and as a methyl donor, contributing to various metabolic processes including the conversion of homocysteine to methionine.
In medical terms, betaine is also used as a dietary supplement and medication. Betaine hydrochloride is a form of betaine that is sometimes used as a supplement to help with digestion by providing additional stomach acid. Betaine anhydrous, on the other hand, is often used as a supplement for improving athletic performance and promoting liver health.
Betaine has also been studied for its potential role in protecting against various diseases, including cardiovascular disease, diabetes, and neurological disorders. However, more research is needed to fully understand its mechanisms of action and therapeutic potential.
Methyltransferases are a class of enzymes that catalyze the transfer of a methyl group (-CH3) from a donor molecule to an acceptor molecule, which is often a protein, DNA, or RNA. This transfer of a methyl group can modify the chemical and physical properties of the acceptor molecule, playing a crucial role in various cellular processes such as gene expression, signal transduction, and DNA repair.
In biochemistry, methyltransferases are classified based on the type of donor molecule they use for the transfer of the methyl group. The most common methyl donor is S-adenosylmethionine (SAM), a universal methyl group donor found in many organisms. Methyltransferases that utilize SAM as a cofactor are called SAM-dependent methyltransferases.
Abnormal regulation or function of methyltransferases has been implicated in several diseases, including cancer and neurological disorders. Therefore, understanding the structure, function, and regulation of these enzymes is essential for developing targeted therapies to treat these conditions.
Methylation, in the context of genetics and epigenetics, refers to the addition of a methyl group (CH3) to a molecule, usually to the nitrogenous base of DNA or to the side chain of amino acids in proteins. In DNA methylation, this process typically occurs at the 5-carbon position of cytosine residues that precede guanine residues (CpG sites) and is catalyzed by enzymes called DNA methyltransferases (DNMTs).
DNA methylation plays a crucial role in regulating gene expression, genomic imprinting, X-chromosome inactivation, and suppression of repetitive elements. Hypermethylation or hypomethylation of specific genes can lead to altered gene expression patterns, which have been associated with various human diseases, including cancer.
In summary, methylation is a fundamental epigenetic modification that influences genomic stability, gene regulation, and cellular function by introducing methyl groups to DNA or proteins.
Protein methyltransferases (PMTs) are a family of enzymes that transfer methyl groups from a donor, such as S-adenosylmethionine (SAM), to specific residues on protein substrates. This post-translational modification plays a crucial role in various cellular processes, including epigenetic regulation, signal transduction, and protein stability.
PMTs can methylate different amino acid residues, such as lysine, arginine, and histidine, on proteins. The methylation of these residues can lead to changes in the charge, hydrophobicity, or interaction properties of the target protein, thereby modulating its function.
For example, lysine methyltransferases (KMTs) are a subclass of PMTs that specifically methylate lysine residues on histone proteins, which are the core components of nucleosomes in chromatin. Histone methylation can either activate or repress gene transcription, depending on the specific residue and degree of methylation.
Protein arginine methyltransferases (PRMTs) are another subclass of PMTs that methylate arginine residues on various protein substrates, including histones, transcription factors, and RNA-binding proteins. Arginine methylation can also affect protein function by altering its interaction with other molecules or modulating its stability.
Overall, protein methyltransferases are essential regulators of cellular processes and have been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases. Therefore, understanding the mechanisms and functions of PMTs is crucial for developing novel therapeutic strategies to target these diseases.
Hyperhomocysteinemia is a medical condition characterized by an excessively high level of homocysteine, an amino acid, in the blood. Generally, a level of 15 micromoles per liter (μmol/L) or higher is considered elevated.
Homocysteine is a byproduct of methionine metabolism, an essential amino acid obtained from dietary proteins. Normally, homocysteine gets converted back to methionine with the help of vitamin B12 and folate (vitamin B9), or it can be converted to another amino acid, cysteine, with the aid of vitamin B6.
Hyperhomocysteinemia can occur due to genetic defects in these enzymes, nutritional deficiencies of vitamins B12, B6, or folate, renal insufficiency, or aging. High homocysteine levels are associated with increased risks of cardiovascular diseases, including atherosclerosis, thrombosis, and stroke. It may also contribute to neurodegenerative disorders like Alzheimer's disease and cognitive decline.
It is essential to diagnose and manage hyperhomocysteinemia early to prevent potential complications. Treatment typically involves dietary modifications, supplementation of the deficient vitamins, and, in some cases, medication.
S-Adenosylmethionine (SAMe) is a physiological compound involved in methylation reactions, transulfuration pathways, and aminopropylation processes in the body. It is formed from the coupling of methionine, an essential sulfur-containing amino acid, and adenosine triphosphate (ATP) through the action of methionine adenosyltransferase enzymes.
SAMe serves as a major methyl donor in various biochemical reactions, contributing to the synthesis of numerous compounds such as neurotransmitters, proteins, phospholipids, nucleic acids, and other methylated metabolites. Additionally, SAMe plays a crucial role in the detoxification process within the liver by participating in glutathione production, which is an important antioxidant and detoxifying agent.
In clinical settings, SAMe supplementation has been explored as a potential therapeutic intervention for various conditions, including depression, osteoarthritis, liver diseases, and fibromyalgia, among others. However, its efficacy remains a subject of ongoing research and debate within the medical community.
Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays a crucial role in the synthesis of DNA, formation of red blood cells, and maintenance of the nervous system. It is involved in the metabolism of every cell in the body, particularly affecting DNA regulation and neurological function.
Vitamin B12 is unique among vitamins because it contains a metal ion, cobalt, from which its name is derived. This vitamin can be synthesized only by certain types of bacteria and is not produced by plants or animals. The major sources of vitamin B12 in the human diet include animal-derived foods such as meat, fish, poultry, eggs, and dairy products, as well as fortified plant-based milk alternatives and breakfast cereals.
Deficiency in vitamin B12 can lead to various health issues, including megaloblastic anemia, fatigue, neurological symptoms such as numbness and tingling in the extremities, memory loss, and depression. Since vitamin B12 is not readily available from plant-based sources, vegetarians and vegans are at a higher risk of deficiency and may require supplementation or fortified foods to meet their daily requirements.
Folic acid is the synthetic form of folate, a type of B vitamin (B9). It is widely used in dietary supplements and fortified foods because it is more stable and has a longer shelf life than folate. Folate is essential for normal cell growth and metabolism, and it plays a critical role in the formation of DNA and RNA, the body's genetic material. Folic acid is also crucial during early pregnancy to prevent birth defects of the brain and spine called neural tube defects.
Medical Definition: "Folic acid is the synthetic form of folate (vitamin B9), a water-soluble vitamin involved in DNA synthesis, repair, and methylation. It is used in dietary supplementation and food fortification due to its stability and longer shelf life compared to folate. Folic acid is critical for normal cell growth, development, and red blood cell production."
Histone-Lysine N-Methyltransferase is a type of enzyme that transfers methyl groups to specific lysine residues on histone proteins. These histone proteins are the main protein components of chromatin, which is the complex of DNA and proteins that make up chromosomes.
Histone-Lysine N-Methyltransferases play a crucial role in the regulation of gene expression by modifying the structure of chromatin. The addition of methyl groups to histones can result in either the activation or repression of gene transcription, depending on the specific location and number of methyl groups added.
These enzymes are important targets for drug development, as their dysregulation has been implicated in various diseases, including cancer. Inhibitors of Histone-Lysine N-Methyltransferases have shown promise in preclinical studies for the treatment of certain types of cancer.
tRNA (transfer RNA) methyltransferases are a group of enzymes that catalyze the transfer of a methyl group (-CH3) to specific positions on the tRNA molecule. These enzymes play a crucial role in modifying and regulating tRNA function, stability, and interaction with other components of the translation machinery during protein synthesis.
The addition of methyl groups to tRNAs can occur at various sites, including the base moieties of nucleotides within the anticodon loop, the TψC loop, and the variable region. These modifications help maintain the structural integrity of tRNA molecules, enhance their ability to recognize specific codons during translation, and protect them from degradation by cellular nucleases.
tRNA methyltransferases are classified based on the type of methylation they catalyze:
1. N1-methyladenosine (m1A) methyltransferases: These enzymes add a methyl group to the N1 position of adenosine residues in tRNAs. An example is TRMT6/TRMT61A, which methylates adenosines at position 58 in human tRNAs.
2. N3-methylcytosine (m3C) methyltransferases: These enzymes add a methyl group to the N3 position of cytosine residues in tRNAs. An example is Dnmt2, which methylates cytosines at position 38 in various organisms.
3. N7-methylguanosine (m7G) methyltransferases: These enzymes add a methyl group to the N7 position of guanosine residues in tRNAs, primarily at position 46 within the TψC loop. An example is Trm8/Trm82, which catalyzes this modification in yeast and humans.
4. 2'-O-methylated nucleotides (Nm) methyltransferases: These enzymes add a methyl group to the 2'-hydroxyl group of ribose sugars in tRNAs, which can occur at various positions throughout the molecule. An example is FTSJ1, which methylates uridines at position 8 in human tRNAs.
5. Pseudouridine (Ψ) synthases: Although not technically methyltransferases, pseudouridine synthases catalyze the isomerization of uridine to pseudouridine, which can enhance tRNA stability and function. An example is Dyskerin (DKC1), which introduces Ψ at various positions in human tRNAs.
These enzymes play crucial roles in modifying tRNAs, ensuring proper folding, stability, and function during translation. Defects in these enzymes can lead to various diseases, including neurological disorders, cancer, and premature aging.
Lipotropic agents are substances that help to promote the breakdown and removal of fats from the liver. They are often used in weight loss supplements because they can help to speed up the metabolism of fat and prevent the accumulation of excess fat in the liver. Some common lipotropic agents include methionine, choline, inositol, and betaine. These compounds work by increasing the production of lecithin, which helps to emulsify fats in the liver and facilitate their transport out of the body. Additionally, lipotropic agents can also help to protect the liver from damage caused by toxins such as alcohol and drugs.
S-Adenosylhomocysteine (SAH) is a metabolic byproduct formed from the demethylation of various compounds or from the breakdown of S-adenosylmethionine (SAM), which is a major methyl group donor in the body. SAH is rapidly hydrolyzed to homocysteine and adenosine by the enzyme S-adenosylhomocysteine hydrolase. Increased levels of SAH can inhibit many methyltransferases, leading to disturbances in cellular metabolism and potential negative health effects.
Protein-Arginine N-Methyltransferases (PRMTs) are a group of enzymes that catalyze the transfer of methyl groups from S-adenosylmethionine to specific arginine residues in proteins, leading to the formation of N-methylarginines. This post-translational modification plays a crucial role in various cellular processes such as signal transduction, DNA repair, and RNA processing. There are nine known PRMTs in humans, which can be classified into three types based on the type of methylarginine produced: Type I (PRMT1, 2, 3, 4, 6, and 8) produce asymmetric dimethylarginines, Type II (PRMT5 and 9) produce symmetric dimethylarginines, and Type III (PRMT7) produces monomethylarginine. Aberrant PRMT activity has been implicated in several diseases, including cancer and neurological disorders.
Sarcosine is not a medical condition or disease, but rather it is an organic compound that is classified as a natural amino acid. It is a metabolite that can be found in the human body, and it is involved in various biochemical processes. Specifically, sarcosine is formed from the conversion of the amino acid glycine by the enzyme glycine sarcosine N-methyltransferase (GSMT) and is then converted to glycine betaine (also known as trimethylglycine) by the enzyme betaine-homocysteine S-methyltransferase (BHMT).
Abnormal levels of sarcosine have been found in various disease states, including cancer. Some studies have suggested that high levels of sarcosine in urine or prostate tissue may be associated with an increased risk of developing prostate cancer or a more aggressive form of the disease. However, more research is needed to confirm these findings and establish the clinical significance of sarcosine as a biomarker for cancer or other diseases.
DNA cytosine methylases are a type of enzyme that catalyze the transfer of a methyl group (-CH3) to the carbon-5 position of the cytosine ring in DNA, forming 5-methylcytosine. This process is known as DNA methylation and plays an important role in regulating gene expression, genomic imprinting, X-chromosome inactivation, and suppression of transposable elements in eukaryotic organisms.
In mammals, the most well-studied DNA cytosine methylases are members of the DNMT (DNA methyltransferase) family, including DNMT1, DNMT3A, and DNMT3B. DNMT1 is primarily responsible for maintaining existing methylation patterns during DNA replication, while DNMT3A and DNMT3B are involved in establishing new methylation patterns during development and differentiation.
Abnormal DNA methylation patterns have been implicated in various diseases, including cancer, where global hypomethylation and promoter-specific hypermethylation can contribute to genomic instability, chromosomal aberrations, and silencing of tumor suppressor genes.
List of EC numbers (EC 2)
List of MeSH codes (D08)
Amino acid synthesis
Diet and cancer
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- In the field of enzymology, a betaine-homocysteine S-methyltransferase also known as betaine-homocysteine methyltransferase (BHMT) is a zinc metallo-enzyme that catalyzes the transfer of a methyl group from trimethylglycine and a hydrogen ion from homocysteine to produce dimethylglycine and methionine respectively: Trimethylglycine (methyl donor) + homocysteine (hydrogen donor) → dimethylglycine (hydrogen receiver) + methionine (methyl receiver) This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. (wikipedia.org)
- In remethylation pathway, Hcy can be remethylated to form Met via methionine synthase (MS) or betaine-homocysteine methyltransferase (BHMT), in which cofactors such as folic acid and vitamin B 12 or betaine are required. (hindawi.com)
- Homocysteine is a sulphur containing amino acid that plays an important role in methionine and folate metabolism. (bmj.com)
- BACKGROUND/AIM: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese. (bvsalud.org)
- This report is a summary of a symposium on the role of S-adenosylmethionine (SAM), betaine, and folate in the treatment of alcoholic liver disease (ALD), which was organized by the National Institute on Alcohol Abuse and Alcoholism in collaboration with the Office of Dietary Supplements and the National Center for Complementary and Alternative Medicine of the National Institutes of Health (Bethesda, MD) and held on 3 October 2005. (nebraska.edu)
- Methylation also requires certain nutrients such as choline, betaine, methionine, folate, vitamins B12 and B6, as well as minerals including magnesium and zinc. (elizabethpattalis.com)
- Simplified picture showing homocysteine involvement in different metabolic pathways, as well as the role of vitamins B-6, B-12, and folate as a co-factors in this pathway. (medscape.com)
- Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B 12 , provide methyl groups for DNA methylation of these pathways. (biomedcentral.com)
- Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation ( r = − 0.13, p = 0.049 and r = − 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. (biomedcentral.com)
- Anomalies may influence the metabolism of homocysteine , which is implicated in disorders ranging from vascular disease, autism, and schizophrenia to neural tube birth defects such as spina bifida. (wikipedia.org)
- Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? (wikipedia.org)
- This study was aimed at investigating the effects of quercetin on mRNA expression and activity of critical enzymes in homocysteine metabolism in rats fed a methionine-enriched diet. (hindawi.com)
- Homocysteine (Hcy) is a nonprotein amino acid, derived from methionine (Met) metabolism [ 1 ]. (hindawi.com)
- Pathways for the metabolism of homocysteine. (bmj.com)
- Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). (biomedcentral.com)
- Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the metabolism of homocysteine was reduced under diabetic conditions, and consequently homocysteine accumulated in the elimination phase. (biomedcentral.com)
- Here, we focused on the fact that a high-fat diet affects the metabolism of both methionine and homocysteine in a diabetic rat model [ 14 ]. (biomedcentral.com)
- To verify this hypothesis, mathematical modeling of methionine metabolism was required to predict the levels of homocysteine derived from given amounts of methionine. (biomedcentral.com)
- As part of this regulation, homocysteine is re-methylated to methionine via two different routes requiring either methionine synthase or betaine-homocysteine methyltransferase. (stackexchange.com)
- The enzymes that the methylation cycle is mediated by include methyltetrahydrofolate reductase (MTHFR), catechol-O-methyltransferase (COMT), and cystathionine beta-synthase (CBS). (elizabethpattalis.com)
Elevated homocysteine levels1
- This should help answer the question: how to people without problematic genetic variants avoid problems associated with elevated homocysteine levels (most notably arteriosclerosis)? (radicalhealing.info)
- These methyltransferases are involved in a very diverse set of pathways including the synthesis of nucleic acids and of certain phospholipids, as well as the methylation of DNA and histones. (stackexchange.com)
- If there is a problem with homocysteine recycling then yes, homocysteine levels would rise, but given that there so many AdoMet-dependent methylation reactions it is unclear how big a contribution PNMT would make to the overall homocysteine load. (stackexchange.com)
- TMG plays an important role in the methylation process as a methyl donor for betaine homocysteine-S-methyltransferase, an enzyme capable of recycling homocysteine to methionine. (bioticsresearch.com)
- Catechol-O-methyltransferase is shown in green boxes. (en-academic.com)
- In humans, catechol- O -methyltransferase protein is encoded by the COMT gene . (en-academic.com)
- Catechol- O -methyltransferase is involved in the inactivation of the catecholamine neurotransmitters ( dopamine , epinephrine , and norepinephrine ). (en-academic.com)
- About 10 years after the discovery of homocystinuria it was hypothesised by McCully 4 that high plasma homocysteine might be causally related to the vascular complications of the disease. (bmj.com)
- When pyridoxine supplementation was initiated at age 18 years, the patient's plasma homocysteine levels decreased below the reference range. (medscape.com)
- At age 50 years, the patient's plasma homocysteine levels still remained low. (medscape.com)
- Betaine may attenuate ALD by increasing the synthesis of SAM and, eventually, glutathione, decreasing the hepatic concentrations of homocysteine and SAH, and increasing the SAM-SAH ratio, which can trigger a cascade of events that lead to the activation of phosphatidylethanolamine methyltransferase, increased phosphatidylcholine synthesis, and formation of VLDL for the export of triacylglycerol from the liver to the circulation. (nebraska.edu)
- The remethylation pathway comprises 2 intersecting biochemical pathways and results in the transfer of a methyl group (CH 3 ) to homocysteine from methylcobalamin, which receives its methyl group from S-adenosylmethionine (SAM), from 5-methyltetrahydrofolate (an active form of folic acid), or from betaine (trimethylglycine). (medscape.com)
- Other possible treatments include the use of folic acid (in pharmacologic doses), betaine (3-methylglycine decreases serum concentrations of homocysteine), or cyanocobalamin, as well as symptomatic supportive measures. (medscape.com)
- Serum homocysteine was significantly increased after methionine treatment and decreased after the addition of quercetin. (hindawi.com)
- It is concluded that quercetin reduces serum homocysteine by increasing remethylation and transsulfuration of homocysteine in rats exposed to a methionine-enriched diet. (hindawi.com)
- Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of homocysteine in the serum and an increased excretion of homocysteine in the urine. (medscape.com)
- However, even when patients' serum betaine concentrations are increased by supplementation, serum homocysteine concentrations are often not lowered to the reference range. (medscape.com)
- Following a low-methionine diet that keeps serum methionine within the reference range may be necessary when treating patients with homocystinuria due to cystathionine beta-synthase deficiency when betaine is administered. (medscape.com)
- Using the methionine loading test, in which 0.1 mg/kg body weight of this amino acid is administered orally, they found that the prevalence of high circulating homocysteine concentrations, or hyperhomocysteinaemia, was higher than in normal controls. (bmj.com)
- The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model. (biomedcentral.com)
- Using our model, we performed simulations to compare the changes in plasma methionine and homocysteine concentrations between ZDF and normal rats, by multiple administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. (biomedcentral.com)
- Additionally, decreased concentrations of homocysteine can down-regulate endoplasmic reticulum stress, which leads to the attenuation of apoptosis and fatty acid synthesis. (nebraska.edu)
- In mammals PNMT is just one member of a large family of methyltransferases which use S -adenosylmethionine (AdoMet) as a cofactor to provide a methyl group. (stackexchange.com)
- Here are 6 enzymes, the first 3 directly convert homocysteine to other amino acids, the other 3 listed here are enzymes which a deficiency of will limit one of those conversions. (radicalhealing.info)
- Unlike EC 18.104.22.168 , EC 22.214.171.124 and EC 126.96.36.199 , this enzyme, from the halophilic methanoarchaeon Methanohalophilus portucalensis, can methylate glycine and all of its intermediates to form the compatible solute betaine. (expasy.org)
- DL-homocysteine inhibits the production of tyrosinase, which is the major pigment enzyme. (medscape.com)
- Conventional treatment of cystathionine beta-synthase deficiency by diet and pyridoxine/betaine normalizes many, but not all, metabolic abnormalities associated with cystathionine beta-synthase deficiency. (medscape.com)
- Thus, 0we hypothesized that long-term administration of a high-methionine diet to T2DM rats with normal renal function may create metabolic changes, culminating in an elevated level of circulating homocysteine. (biomedcentral.com)
- What is the relationship between Homocysteine and Norepinephrine metabolic cycles? (stackexchange.com)
- Homocysteine is actually a by product of certain normal metabolic amino acid breakdown and processing. (ecopolitan.com)
- Genes encoding homocysteine methyltransferase (HMT) have been identified in some plant species in response to abiotic stress, but its molecular mechanism in plant drought tolerance remains unclear. (bvsalud.org)
- Choline acts to reduce harmful levels of the amino acid homocysteine, converting it to the beneficial chemical methionine. (azbio.org)
- First, choline reduces levels of homocysteine‚ an amino acid that can act as a potent neurotoxin, contributing to the hallmarks of Alzheimer's disease: neurodegeneration and the formation of amyloid plaques. (azbio.org)
- Choline performs a chemical transformation, converting the harmful homocysteine into the helpful chemical methionine. (azbio.org)
- An alternative remethylation pathway also exists using the cobalamin independent betaine-homocysteine methyltransferase. (bmj.com)
- As a universal key intermediate in the MMC, homocysteine is not obtained from the diet, but is remethylated to methionine, or converted to cysteine by the trans-sulfuration pathway. (biomedcentral.com)
- One of my genetic defects affects my ability to break down betaine into the free amino acids glycine and methionine (roughly, I would have to review the chemistry for the specifics). (effectiveselfcare.info)
- Homocysteine is known to double the risk of developing Alzheimer's disease and is found in elevated levels in patients with Alzheimer's disease. (azbio.org)
- The levels of methionine and homocysteine were elevated approximately two- and three-fold, respectively, in ZDF rats, while there were no changes observed in the normal control rats. (biomedcentral.com)
- 2009) Glycine N -methyltransferase and regulation of S -adenosylmethionine levels. (stackexchange.com)
- In conclusion, my answer to your question is that it is unlikely that stress leads to elevated levels of homocysteine as long as all of the relevant regulatory machinery is functioning correctly. (stackexchange.com)
- Homocysteine Reduction Formula, a special nutritional supplement created by Brimhall, can also lower homocysteine levels. (medscape.com)
- In patients with hypothyroidism, treatment with L-thyroxine can normalize homocysteine levels. (medscape.com)
- The diagram appears to state that Dopamine gets converted to Norepinephrine , which gets converted to Epinephrine, and as a side effect, Homocysteine cycle gets advanced too (or is it involved? (stackexchange.com)
- Norepinephrine is converted to epinephrine by phenylethanolamine N -methyltransferase (PNMT). (stackexchange.com)
- By what mechanism does elevated homocysteine level cause endothelial dysfunction and damage? (stackexchange.com)
- By what mechanism does elevated homocysteine level accelerate thrombin formation? (stackexchange.com)
- Betaine therapy can precipitate cerebral edema, although the exact mechanism is uncertain. (medscape.com)
- consider betaine as an adjunct, not an alternative, to dietary control. (medscape.com)
- Glycine N -methyltransferase deficiency: a new patient with a novel mutation. (medscape.com)
- These results can be interpreted to mean that both methionine and homocysteine will accumulate in patients with T2DM, who regularly consume high-methionine foods. (biomedcentral.com)
- What is the role of Homocysteine in cognitive function? (stackexchange.com)