25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Mixed Function Oxygenases
Bile Acids and Salts
Adrenal Hyperplasia, Congenital
Hydroxymethylglutaryl CoA Reductases
Hypoxia-Inducible Factor 1, alpha Subunit
Cytochrome P-450 Enzyme System
ATP Binding Cassette Transporter 1
Receptors, Adrenergic, alpha
Molecular Sequence Data
ATP-Binding Cassette Transporters
Hypoxia-Inducible Factor-Proline Dioxygenases
Cholesterol Ester Transfer Proteins
Amino Acid Sequence
Hydroxymethylglutaryl-CoA Reductase Inhibitors
alpha7 Nicotinic Acetylcholine Receptor
Gene Expression Regulation
Dose-Response Relationship, Drug
Orphan Nuclear Receptors
Cholesterol Side-Chain Cleavage Enzyme
Rats, Inbred Strains
Scavenger Receptors, Class B
Gene Expression Regulation, Enzymologic
Aryl Hydrocarbon Hydroxylases
Receptors, Adrenergic, alpha-2
Receptors, Adrenergic, alpha-1
Chromatography, High Pressure Liquid
Electrophoresis, Polyacrylamide Gel
Sterol Regulatory Element Binding Protein 2
Reverse Transcriptase Polymerase Chain Reaction
Receptors, Cytoplasmic and Nuclear
Chinese hamster ovary cells require the coexpression of microsomal triglyceride transfer protein and cholesterol 7alpha-hydroxylase for the assembly and secretion of apolipoprotein B-containing lipoproteins. (1/481)Due to the absence of microsomal triglyceride transfer protein (MTP), Chinese hamster ovary (CHO) cells lack the ability to translocate apoB into the lumen of the endoplasmic reticulum, causing apoB to be rapidly degraded by an N-acetyl-leucyl-leucyl-norleucinal-inhibitable process. The goal of this study was to examine if expression of MTP, whose genetic deletion is responsible for the human recessive disorder abetalipoproteinemia, would recapitulate the lipoprotein assembly pathway in CHO cells. Unexpectedly, expression of MTP mRNA and protein in CHO cells did not allow apoB-containing lipoproteins to be assembled and secreted by CHO cells expressing apoB53. Although expression of MTP in cells allowed apoB to completely enter the endoplasmic reticulum, it was degraded by a proteolytic process that was inhibited by dithiothreitol (1 mM) and chloroquine (100 microM), but resistant to N-acetyl-leucyl-leucyl-norleucinal. In marked contrast, coexpression of the liver-specific gene product cholesterol 7alpha-hydroxylase with MTP resulted in levels of MTP lipid transfer activity that were similar to those in mouse liver and allowed intact apoB53 to be secreted as a lipoprotein particle. These data suggest that, although MTP-facilitated lipid transport is not required for apoB translocation, it is required for the secretion of apoB-containing lipoproteins. We propose that, in CHO cells, MTP plays two roles in the assembly and secretion of apoB-containing lipoproteins: 1) it acts as a chaperone that facilitates apoB53 translocation, and 2) its lipid transfer activity allows apoB-containing lipoproteins to be assembled and secreted. Our results suggest that the phenotype of the cell (e.g. expression of cholesterol 7alpha-hydroxylase by the liver) may profoundly influence the metabolic relationships determining how apoB is processed into lipoproteins and/or degraded. (+info)
The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil. (2/481)Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body. (+info)
High plasma cholesterol in drug-induced cholestasis is associated with enhanced hepatic cholesterol synthesis. (3/481)In alpha-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7alpha-hydroxylase activity was decreased by approximately 70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma. (+info)
Identification of a nuclear receptor for bile acids. (4/481)Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport. (+info)
CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene. (5/481)Cholesterol 7alpha-hydroxylase is the first and rate-limiting enzyme in a pathway through which cholesterol is metabolized to bile acids. The gene encoding cholesterol 7alpha-hydroxylase, CYP7A, is expressed exclusively in the liver. Overexpression of CYP7A in hamsters results in a reduction of serum cholesterol levels, suggesting that the enzyme plays a central role in cholesterol homeostasis. Here, we report the identification of a hepatic-specific transcription factor that binds to the promoter of the human CYP7A gene. We designate this factor CPF, for CYP7A promoter binding factor. Mutation of the CPF binding site within the CYP7A promoter abolished hepatic-specific expression of the gene in transient transfection assays. A cDNA encoding CPF was cloned and identified as a human homolog of the Drosophila orphan nuclear receptor fushi tarazu F1 (Ftz-F1). Cotransfection of a CPF expression plasmid and a CYP7A reporter gene resulted in specific induction of CYP7A-directed transcription. These observations suggest that CPF is a key regulator of human CYP7A gene expression in the liver. (+info)
Lipoprotein cholesterol uptake mediates up-regulation of bile-acid synthesis by increasing cholesterol 7alpha-hydroxylase but not sterol 27-hydroxylase gene expression in cultured rat hepatocytes. (6/481)Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7alpha-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different lipoproteins in regulating both enzymes are not well established. We studied the effect of different rabbit lipoproteins on cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase in cultured rat hepatocytes. beta-Migrating very-low-density lipoprotein (betaVLDL) and intermediate-density lipoprotein (IDL) caused a significant increase in the intracellular cholesteryl ester content of cells (2. 3- and 2-fold, respectively) at a concentration of 200 microgram of cholesterol/ml, whereas high-density lipoprotein (HDL, 50% v/v), containing no apolipoprotein E (apo E), showed no effect after a 24-h incubation. betaVLDL and IDL increased bile-acid synthesis (1. 9- and 1.6-fold, respectively) by up-regulation of cholesterol 7alpha-hydroxylase activity (1.7- and 1.5-fold, respectively). Dose- and time-dependent changes in cholesterol 7alpha-hydroxylase mRNA levels and gene expression underlie the increase in enzyme activity. Incubation of cells with HDL showed no effect. Sterol 27-hydroxylase gene expression was not affected by any of the lipoproteins added. Transient-expression experiments in hepatocytes, transfected with a promoter-reporter construct containing the proximal 348 nucleotides of the rat cholesterol 7alpha-hydroxylase promoter, showed an enhanced gene transcription (2-fold) with betaVLDL, indicating that a sequence important for a cholesterol-induced transcriptional response is located in this part of the cholesterol 7alpha-hydroxylase gene. The extent of stimulation of cholesterol 7alpha-hydroxylase is associated with the apo E content of the lipoprotein particle, which is important in the uptake of lipoprotein cholesterol. We conclude that physiological concentrations of cholesterol in apo E-containing lipoproteins increase bile-acid synthesis by stimulating cholesterol 7alpha-hydroxylase gene transcription, whereas HDL has no effect and sterol 27-hydroxylase is not affected. (+info)
Selective uptake of cholesteryl ester from low density lipoprotein is involved in HepG2 cell cholesterol homeostasis. (7/481)Low density lipoprotein (LDL) can follow either a holoparticle uptake pathway, initiated by the LDL receptor (LDLr), and be completely degraded, or it can deliver its cholesteryl esters (CE) selectively to HepG2 cells. Although high density lipoprotein-CE selective uptake has been shown to be linked to cell cholesterol homeostasis in nonhepatic cells, there is no available information on the effect of LDL-CE selective uptake on hepatic cell cholesterol homeostasis. In order to define the role of the LDL-CE selective uptake pathway in hepatic cell cholesterol homeostasis, we used a cellular model that expresses constitutively a LDLr antisense mRNA and that shows LDLr activity at 31% the normal level (HepG2-all cells). The addition of a specific antibody anti-LDLr (IgG-C7) reduces LDL protein degradation (LDLr activity) to 7%. This cellular model therefore reflects, above all, LDL-CE selective uptake activity when incubated with LDL. The inactivation of LDLr reduces LDL-protein association by 78% and LDL-CE association by only 43%. The LDL-CE selective uptake was not reduced by the inactivation of LDLr. The activities of the various enzymes involved in cell cholesterol homeostasis were measured in normal and LDLr-deficient cells during incubation in the absence or presence of LDL as a cholesterol source. Essentially, 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase (ACAT) activities responded to LDL in LDLr-deficient cells as well as in normal HepG2 cells. Inhibition of lysosomal hydrolysis with chloroquine abolished the effect measured on ACAT activity in the presence of LDL, suggesting that CE of LDL, but not free cholesterol, maintains cell cholesterol homeostasis. Thus, in HepG2 cells, when LDLr function is virtually abolished, LDL-CE selective uptake is coupled to cell cholesterol homeostasis. (+info)
Bile acid synthesis in the Smith-Lemli-Opitz syndrome: effects of dehydrocholesterols on cholesterol 7alpha-hydroxylase and 27-hydroxylase activities in rat liver. (8/481)The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway. The patients have reduced plasma and tissue cholesterol concentrations with the accumulation of 7-dehydrocholesterol and 8-dehydrocholesterol. Bile acid synthesis is reduced and unnatural cholenoic and cholestenoic acids have been identified in some SLOS patients. To explore the mechanism of the abnormal bile acid production, the activities of key enzymes in classic and alternative bile acid biosynthetic pathways (microsomal cholesterol 7alpha-hydroxylase and mitochondrial sterol 27-hydroxylase) were measured in liver biopsy specimens from two mildly affected SLOS patients. The effects of 7- and 8-dehydrocholesterols on these two enzyme activities were studied by using liver from SLOS model rats that were treated with the Delta(7)-reductase inhibitor (BM15.766) for 4 months and were comparable with more severe SLOS phenotype in plasma and hepatic sterol compositions. In the SLOS patients, cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase were not defective. In BM15.766-treated rats, both enzyme activities were lower than those in control rats and they were competitively inhibited by 7- and 8-dehydrocholesterols. Rat microsomal cholesterol 7alpha-hydroxylase did not transform 7-dehydrocholesterol or 8-dehydrocholesterol into 7alpha-hydroxylated sterols. In contrast, rat mitochondrial sterol 27-hydroxylase catalyzed 27-hydroxylation of 7- and 8-dehydrocholesterols, which were partially converted to 3beta-hydroxycholestadienoic acids. Addition of microsomes to the mitochondrial 27-hydroxylase assay mixture reduced 27-hydroxydehydrocholesterol concentrations, which suggested that 27-hydroxydehydrocholesterols were further metabolized by microsomal enzymes. These results suggest that reduced normal bile acid production is characteristic of severe SLOS phenotype and is caused not only by depletion of hepatic cholesterol but also by competitive inhibition of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by accumulated 7- and 8-dehydrocholesterols. Unnatural bile acids are synthesized mainly by the alternative pathway via mitochondrial sterol 27-hydroxylase in SLOS. (+info)
There are several types of hypercholesterolemia, including:
1. Familial hypercholesterolemia: This is an inherited condition that causes high levels of low-density lipoprotein (LDL) cholesterol, also known as "bad" cholesterol, in the blood.
2. Non-familial hypercholesterolemia: This type of hypercholesterolemia is not inherited and can be caused by a variety of factors, such as a high-fat diet, lack of exercise, obesity, and certain medical conditions, such as hypothyroidism or polycystic ovary syndrome (PCOS).
3. Mixed hypercholesterolemia: This type of hypercholesterolemia is characterized by high levels of both LDL and high-density lipoprotein (HDL) cholesterol in the blood.
The diagnosis of hypercholesterolemia is typically made based on a physical examination, medical history, and laboratory tests, such as a lipid profile, which measures the levels of different types of cholesterol and triglycerides in the blood. Treatment for hypercholesterolemia usually involves lifestyle changes, such as a healthy diet and regular exercise, and may also include medication, such as statins, to lower cholesterol levels.
There are three main forms of ACH:
1. Classic congenital adrenal hyperplasia (CAH): This is the most common form of ACH, accounting for about 90% of cases. It is caused by mutations in the CYP21 gene, which codes for an enzyme that converts cholesterol into cortisol and aldosterone.
2. Non-classic CAH (NCAH): This form of ACH is less common than classic CAH and is caused by mutations in other genes involved in cortisol and aldosterone production.
3. Mineralocorticoid excess (MOE) or glucocorticoid deficiency (GD): These are rare forms of ACH that are characterized by excessive production of mineralocorticoids (such as aldosterone) or a deficiency of glucocorticoids (such as cortisol).
The symptoms of ACH can vary depending on the specific form of the disorder and the age at which it is diagnosed. In classic CAH, symptoms typically appear in infancy and may include:
* Premature puberty (in girls) or delayed puberty (in boys)
* Abnormal growth patterns
* Distended abdomen
* Weight gain or obesity
* Easy bruising or bleeding
In NCAH and MOE/GD, symptoms may be less severe or may not appear until later in childhood or adulthood. They may include:
* High blood pressure
* Low blood sugar (hypoglycemia)
* Weight gain or obesity
* Mood changes
If left untreated, ACH can lead to serious complications, including:
* Adrenal gland insufficiency
* Heart problems
* Bone health problems
* Increased risk of infections
* Mental health issues (such as depression or anxiety)
Treatment for ACH typically involves hormone replacement therapy to restore the balance of hormones in the body. This may involve taking medications such as cortisol, aldosterone, or other hormones to replace those that are deficient or imbalanced. In some cases, surgery may be necessary to remove an adrenal tumor or to correct physical abnormalities.
With proper treatment, many individuals with ACH can lead healthy, active lives. However, it is important for individuals with ACH to work closely with their healthcare providers to manage their condition and prevent complications. This may involve regular check-ups, hormone level monitoring, and lifestyle changes such as a healthy diet and regular exercise.
There are several types of hyperlipidemia, including:
1. High cholesterol: This is the most common type of hyperlipidemia and is characterized by elevated levels of low-density lipoprotein (LDL) cholesterol, also known as "bad" cholesterol.
2. High triglycerides: This type of hyperlipidemia is characterized by elevated levels of triglycerides in the blood. Triglycerides are a type of fat found in the blood that is used for energy.
3. Low high-density lipoprotein (HDL) cholesterol: HDL cholesterol is known as "good" cholesterol because it helps remove excess cholesterol from the bloodstream and transport it to the liver for excretion. Low levels of HDL cholesterol can contribute to hyperlipidemia.
Symptoms of hyperlipidemia may include xanthomas (fatty deposits on the skin), corneal arcus (a cloudy ring around the iris of the eye), and tendon xanthomas (tender lumps under the skin). However, many people with hyperlipidemia have no symptoms at all.
Hyperlipidemia can be diagnosed through a series of blood tests that measure the levels of different types of cholesterol and triglycerides in the blood. Treatment for hyperlipidemia typically involves dietary changes, such as reducing intake of saturated fats and cholesterol, and increasing physical activity. Medications such as statins, fibric acid derivatives, and bile acid sequestrants may also be prescribed to lower cholesterol levels.
In severe cases of hyperlipidemia, atherosclerosis (hardening of the arteries) can occur, which can lead to cardiovascular disease, including heart attacks and strokes. Therefore, it is important to diagnose and treat hyperlipidemia early on to prevent these complications.
There are several types of PKU, including classic PKU, mild PKU, and hyperphenylalaninemia (HPA). Classic PKU is the most severe form of the disorder and is characterized by a complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is necessary for the breakdown of Phe. Mild PKU is characterized by a partial deficiency of PAH, while HPA is caused by a variety of other genetic defects that affect the breakdown of Phe.
Symptoms of PKU can vary depending on the severity of the disorder, but may include developmental delays, intellectual disability, seizures, and behavioral problems. If left untreated, PKU can lead to serious health complications such as brain damage, seizures, and even death.
The primary treatment for PKU is a strict diet that limits the intake of Phe. This typically involves avoiding foods that are high in Phe, such as meat, fish, eggs, and dairy products, and consuming specialized medical foods that are low in Phe. In some cases, medication may also be prescribed to help manage symptoms.
PKU is an autosomal recessive disorder, which means that it is inherited in an unusual way. Both parents must carry the genetic mutation that causes PKU, and each child has a 25% chance of inheriting the disorder. PKU can be diagnosed through newborn screening, which is typically performed soon after birth. Early diagnosis and treatment can help prevent or minimize the symptoms of PKU and improve quality of life for individuals with the disorder.
Arteriosclerosis can affect any artery in the body, but it is most commonly seen in the arteries of the heart, brain, and legs. It is a common condition that affects millions of people worldwide and is often associated with aging and other factors such as high blood pressure, high cholesterol, diabetes, and smoking.
There are several types of arteriosclerosis, including:
1. Atherosclerosis: This is the most common type of arteriosclerosis and occurs when plaque builds up inside the arteries.
2. Arteriolosclerosis: This type affects the small arteries in the body and can cause decreased blood flow to organs such as the kidneys and brain.
3. Medial sclerosis: This type affects the middle layer of the artery wall and can cause stiffness and narrowing of the arteries.
4. Intimal sclerosis: This type occurs when plaque builds up inside the innermost layer of the artery wall, causing it to become thick and less flexible.
Symptoms of arteriosclerosis can include chest pain, shortness of breath, leg pain or cramping during exercise, and numbness or weakness in the limbs. Treatment for arteriosclerosis may include lifestyle changes such as a healthy diet and regular exercise, as well as medications to lower blood pressure and cholesterol levels. In severe cases, surgery may be necessary to open up or bypass blocked arteries.
Cholelithiasis is a common condition that affects millions of people worldwide. It can occur at any age but is more common in adults over 40 years old. Women are more likely to develop cholelithiasis than men, especially during pregnancy or after childbirth.
The symptoms of cholelithiasis can vary depending on the size and location of the gallstones. Some people may not experience any symptoms at all, while others may have:
* Abdominal pain, especially in the upper right side of the abdomen
* Nausea and vomiting
* Shaking or chills
* Loss of appetite
* Yellowing of the skin and eyes (jaundice)
If left untreated, cholelithiasis can lead to complications such as inflammation of the gallbladder (cholangitis), infection of the bile ducts (biliary sepsis), or blockage of the common bile duct. These complications can be life-threatening and require immediate medical attention.
The diagnosis of cholelithiasis is usually made through a combination of imaging tests such as ultrasound, CT scan, or MRI, and blood tests to check for signs of inflammation and liver function. Treatment options for cholelithiasis include:
* Watchful waiting: If the gallstones are small and not causing any symptoms, doctors may recommend monitoring the condition without immediate treatment.
* Medications: Oral medications such as bile salts or ursodiol can dissolve small gallstones and relieve symptoms.
* Laparoscopic cholecystectomy: A minimally invasive surgical procedure to remove the gallbladder through small incisions.
* Open cholecystectomy: An open surgery to remove the gallbladder, usually performed when the gallstones are large or there are other complications.
It is important to seek medical attention if you experience any symptoms of cholelithiasis, as early diagnosis and treatment can help prevent complications and improve outcomes.
The hallmark feature of CTX is the presence of xanthomas, which are fatty deposits that accumulate in the brain and spinal cord. These deposits can cause inflammation and damage to the surrounding tissue, leading to a range of neurological symptoms.
CTX is usually diagnosed through a combination of clinical evaluation, imaging studies such as MRI or CT scans, and laboratory tests to identify the genetic mutations responsible for the condition. There is currently no cure for CTX, but treatment options may include medications to manage seizures and other symptoms, as well as surgery to remove xanthomas in some cases.
There are three main types of Niemann-Pick diseases:
1. Type A: This is the most common and severe form of the disease, and it typically affects infants before the age of one. It is characterized by progressive loss of motor skills, seizures, and death before the age of two.
2. Type B: This form of the disease usually presents in adulthood and is characterized by gradually worsening neurological symptoms, including muscle weakness, ataxia (loss of coordination), and dementia. Life expectancy for individuals with type B Niemann-Pick disease is typically between 20 and 40 years.
3. Type C: This form of the disease is less severe than types A and B and is often diagnosed in childhood or adolescence. It is characterized by a range of symptoms, including developmental delays, learning disabilities, and mild neurological problems.
Niemann-Pick diseases are caused by mutations in the genes that code for proteins involved in lipid metabolism. These proteins play a crucial role in the transport of lipids within cells, particularly in the brain and other organs. Without these proteins, lipids accumulate in cells and cause damage to their membranes and organelles.
There is currently no cure for Niemann-Pick diseases, but researchers are working on developing new treatments that may help alleviate some of the symptoms and slow the progression of the disease. These treatments include enzyme replacement therapy, gene therapy, and small molecule therapies. In addition, clinical trials are underway to evaluate the safety and effectiveness of these new treatments in humans.
In summary, Niemann-Pick diseases are a group of rare and severe genetic disorders that affect the transport of lipids within cells. There is currently no cure for these diseases, but researchers are working on developing new treatments that may help alleviate some of the symptoms and slow the progression of the disease.
Answer: Type A, B, and C Niemann-Pick disease are three forms of a group of rare genetic disorders that affect lipid metabolism, with types A and B being more severe and type C being less severe.
Body weight is an important health indicator, as it can affect an individual's risk for certain medical conditions, such as obesity, diabetes, and cardiovascular disease. Maintaining a healthy body weight is essential for overall health and well-being, and there are many ways to do so, including a balanced diet, regular exercise, and other lifestyle changes.
There are several ways to measure body weight, including:
1. Scale: This is the most common method of measuring body weight, and it involves standing on a scale that displays the individual's weight in kg or lb.
2. Body fat calipers: These are used to measure body fat percentage by pinching the skin at specific points on the body.
3. Skinfold measurements: This method involves measuring the thickness of the skin folds at specific points on the body to estimate body fat percentage.
4. Bioelectrical impedance analysis (BIA): This is a non-invasive method that uses electrical impulses to measure body fat percentage.
5. Dual-energy X-ray absorptiometry (DXA): This is a more accurate method of measuring body composition, including bone density and body fat percentage.
It's important to note that body weight can fluctuate throughout the day due to factors such as water retention, so it's best to measure body weight at the same time each day for the most accurate results. Additionally, it's important to use a reliable scale or measuring tool to ensure accurate measurements.
The most common form of xanthomatosis is called familial hypercholesterolemia, which is caused by a deficiency of low-density lipoprotein (LDL) receptors in the body. This results in high levels of LDL cholesterol in the blood, which can lead to the accumulation of cholesterol and other lipids in the skin, eyes, and other tissues.
Other forms of xanthomatosis include:
* Familial apo A-1 deficiency: This is a rare disorder caused by a deficiency of apolipoprotein A-1 (apoA-1), a protein that plays a critical role in the transportation of triglycerides and cholesterol in the blood.
* familial hyperlipidemia: This is a group of rare genetic disorders that are characterized by high levels of lipids in the blood, including cholesterol and triglycerides.
* Chylomicronemia: This is a rare disorder caused by a deficiency of lipoprotein lipase, an enzyme that breaks down triglycerides in the blood.
The symptoms of xanthomatosis vary depending on the specific form of the condition and the organs affected. They may include:
* Yellowish deposits (xanthomas) on the skin, particularly on the elbows, knees, and buttocks
* Deposits in the eyes (corneal arcus)
* Fatty liver disease
* High levels of cholesterol and triglycerides in the blood
* Abdominal pain
* Weight loss
Treatment for xanthomatosis typically involves managing the underlying genetic disorder, which may involve dietary changes, medication, or other therapies. In some cases, surgery may be necessary to remove affected tissue.
In summary, xanthomatosis is a group of rare genetic disorders that are characterized by deposits of lipids in the skin and other organs. The symptoms and treatment vary depending on the specific form of the condition.
The disease begins with endothelial dysfunction, which allows lipid accumulation in the artery wall. Macrophages take up oxidized lipids and become foam cells, which die and release their contents, including inflammatory cytokines, leading to further inflammation and recruitment of more immune cells.
The atherosclerotic plaque can rupture or ulcerate, leading to the formation of a thrombus that can occlude the blood vessel, causing ischemia or infarction of downstream tissues. This can lead to various cardiovascular diseases such as myocardial infarction (heart attack), stroke, and peripheral artery disease.
Atherosclerosis is a multifactorial disease that is influenced by genetic and environmental factors such as smoking, hypertension, diabetes, high cholesterol levels, and obesity. It is diagnosed by imaging techniques such as angiography, ultrasound, or computed tomography (CT) scans.
Treatment options for atherosclerosis include lifestyle modifications such as smoking cessation, dietary changes, and exercise, as well as medications such as statins, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors. In severe cases, surgical interventions such as bypass surgery or angioplasty may be necessary.
In conclusion, atherosclerosis is a complex and multifactorial disease that affects the arteries and can lead to various cardiovascular diseases. Early detection and treatment can help prevent or slow down its progression, reducing the risk of complications and improving patient outcomes.
The symptoms of SLOS can vary in severity and may include:
1. Developmental delays and intellectual disability
2. Distinctive facial features, such as a prominent forehead, narrow eyes, and a short nose
3. Skeletal abnormalities, including short stature, joint deformities, and scoliosis
4. Heart defects, such as atrial septal defects or ventricular septal defects
5. Kidney problems, such as kidney stones or chronic kidney disease
6. Vision problems, such as cataracts or glaucoma
7. Hearing loss or deafness
8. Increased risk of infections
9. Poor muscle tone and coordination
10. Delayed motor milestones
SLOS is usually diagnosed by a combination of clinical evaluation, laboratory tests, and genetic analysis. Treatment is focused on managing the symptoms and preventing complications. This may include medications to control seizures, physical therapy to improve muscle tone and coordination, and speech and language therapy to address communication difficulties.
The prognosis for individuals with SLOS varies depending on the severity of the mutation and the presence of other health problems. Some individuals with mild forms of the disorder may have a relatively normal life expectancy, while others with more severe forms may have a shorter life span. Early diagnosis and intervention are critical to improving outcomes for individuals with SLOS.
Cholesterol 7 alpha-hydroxylase
Farnesoid X receptor
List of MeSH codes (D08)
List of MeSH codes (D12.776)
Liver receptor homolog-1
Liver X receptor alpha
25-Hydroxyvitamin D 1-alpha-hydroxylase
Cytochrome P450 omega hydroxylase
Citric acid cycle
List of diseases (C)
Pharmacology of bicalutamide
Polycystic ovary syndrome
List of enzymes
Pharmacodynamics of progesterone
Disorders of sex development
Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors
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- 20. Genomic cloning, sequencing, and analysis of the hamster cholesterol 7 alpha-hydroxylase gene (CYP7). (nih.gov)
- This enzyme, encoded by CYP7 , converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS . (nih.gov)
- Esta enzima, codificada por CYP7, convierte el colesterol en 7-alfa-hidroxicolesterol, que es el paso primero y limitante de la síntesis de los ÁCIDOS Y SALES BILIARES. (bvsalud.org)
- In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7α-hydroxylase (CYP7). (elsevierpure.com)
- Hormonal regulation of the cholesterol 7 alpha-hydroxylase gene (CYP7). (omeka.net)
- The transcriptional regulation of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) by hormones and signal transduction pathways was studied by transient transfection assay of the promoter activity. (omeka.net)
- Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors. (omeka.net)
- The gene encoding cholesterol 7alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. (omeka.net)
- Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. (nih.gov)
- The catabolism of cholesterol into bile acids is regulated by oxysterols and bile acids, which induce or repress transcription of the pathway's rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1). (nih.gov)
- HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1). (omeka.net)
- The gene for cholesterol 7alpha-hydroxylase (CYP7A1) contains a sequence at nt -149 to -118 that was found to play a large role in determining the overall transcriptional activity and regulation of the promoter. (omeka.net)
- Regulation of cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRalpha). (omeka.net)
- The cholesterol 7alpha-hydroxylase gene (CYP7A1) plays an important role in regulation of bile acid biosynthesis and cholesterol homeostasis. (omeka.net)
- Farnesoid X receptor responds to bile acids and represses cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription. (omeka.net)
- Cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription is repressed by bile acids. (omeka.net)
- Nuclear receptor-mediated repression of human cholesterol 7alpha-hydroxylase gene transcription by bile acids. (omeka.net)
- Hydrophobic bile acids strongly repressed transcription of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) in the bile acid biosynthetic pathway in the liver. (omeka.net)
- This gene provides instructions for making an enzyme called oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
- In the brain, oxysterol 7-alpha-hydroxylase is involved in a pathway that converts cholesterol to hormones called neurosteroids. (medlineplus.gov)
- Oxysterol 7-alpha-hydroxylase helps maintain normal cholesterol levels in the brain and, by producing neurosteroids through altering existing hormones within the pathway, regulates the effects of neurosteroids on the brain. (medlineplus.gov)
- CYP7B1 gene mutations that cause spastic paraplegia type 5A reduce or eliminate the activity of oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
- In the brain, a decrease in enzyme activity results in an accumulation of cholesterol and alters neurosteroid production triggered by oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
- In the liver, oxysterol 7-alpha-hydroxylase is involved in the pathway that breaks down a waxy, fat-like substance called cholesterol to form a bile acid called chenodeoxycholic acid. (nih.gov)
- Most CYP7B1 gene mutations change single protein building blocks (amino acids) in the oxysterol 7-alpha-hydroxylase enzyme. (nih.gov)
- Reduced oxysterol 7-alpha-hydroxylase enzyme activity does not seem to affect cholesterol breakdown or bile acid production in the liver. (nih.gov)
- Another pathway in the liver can perform these functions, which may explain why reduction of oxysterol 7-alpha-hydroxylase activity does not impact liver function. (nih.gov)
- Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1. (omeka.net)
- Oxysterol 7 alpha-hydroxylase catalyzes hydroxylation of oxysterols and neurosterols and plays a role in the alternative bile acid synthesis pathway. (omeka.net)
- Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. (nih.gov)
- Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. (nih.gov)
- A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. (biomedcentral.com)
- Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine. (biomedcentral.com)
- Taurine could enhance CYP7A1 expression by inducing HNF4α and inhibiting MEK1/2 and p-c-Jun expressions to promote intracellular cholesterol metabolism. (biomedcentral.com)
- Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the major bile acids synthetic pathway, is widely reported to be regulated by several nuclear receptors at the level of gene transcription [ 8 - 10 ]. (biomedcentral.com)
- The in vitro studies have focused on the upregulating-effect of taurine on CYP7A1 mRNA level, but the regulatory mechanism and the changes of cellular bile acids, the products of cholesterol degradation, have not been discussed. (biomedcentral.com)
- reported that taurine almost did not alter the mRNA levels of LXRα, LRH-1, FXR and SHP-1 of mice with high cholesterol or cholesterol/sodium cholate diets, although CYP7A1 mRNA level was significantly decreased by cholesterol/sodium cholate diet and then two-fold increased by taurine supplementation [ 18 ]. (biomedcentral.com)
- Their results suggested that FXR was indeed activated by cholesterol/sodium cholate diet and then functioned as a down-regulator to CYP7A1 in spite of no change of mRNA level, and that taurine might stimulate CYP7A1 expression not by repressing FXR-dependent pathway but by FXR-independent pathway. (biomedcentral.com)
- In the present study, HepG2 cell line derived from human hepatoma cell was used to investigate the dose- and time-dependent effects of taurine with a focus on the change of CYP7A1 expression and the concentration of cholesterol and bile acids. (biomedcentral.com)
- 7. Structure and expression of the Kas12 gene encoding a beta-ketoacyl-acyl carrier protein synthase I isozyme from barley. (nih.gov)
- 16. Human alpha 2(VI) collagen gene. (nih.gov)
- Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha). (omeka.net)
- Publication: Quantile-Dependent Expressivity and Gene-Lifestyle Interactions Involving High-Density Lipoprotein Cholesterol. (nih.gov)
- Key Message: Quantile-dependent expressivity provides a potential explanation for some reported gene-lifestyle interactions for HDL-cholesterol. (nih.gov)
- Metyrapone, an inhibitor of 11 beta-hydroxylase, and SC 12937 and AY 9944, inhibitors of cholesterol synthesis, did not prevent ovulation or the progesterone rise induced by exogenous LH. (lookformedical.com)
- The effects of the two sequestrants on faecal bile acid excretion, plasma total cholesterol, VLDL + LDL and HDL cholesterol and triglyceride concentrations and on liver enzymes involved in the synthesis and metabolism of cholesterol were investigated in normocholesterolaemic hamsters. (nih.gov)
- Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyses sterol side-chain oxidation of bile acid synthesis from cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. (omeka.net)
- Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. (nih.gov)
- Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. (illumina.com)
- The impacted bile acid profile was consistent with altered expression of ileal bile acid transporter genes and hepatic bile acid synthesis genes, supporting the potential role of Parasutterella in bile acid maintenance and cholesterol metabolism. (nature.com)
- The enzyme primarily converts the neurosteroid dehydroepiandrosterone (DHEA) into 7-hydroxy-DHEA. (nih.gov)
- A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE . (nih.gov)
- Vitamin C is required for lysyl hydroxylase, an enzyme responsible for attaching the lysine residues together on adjacent collagen strands. (jeffreydachmd.com)
- Above image shows three steps in attachment of two fibrils (collagen strands) by combining two lysine molecules with the help of an enzyme lysine hydroxylase which requires vitamin C. (jeffreydachmd.com)
- The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively. (biomedcentral.com)
- Furthermore, many studies indicate that the cholesterol-lowering effect of taurine is due to the increased biotransformation of cholesterol to bile acids in the liver and the subsequent excretion of bile acids in feces [ 5 - 7 ]. (biomedcentral.com)
- Cholesterol conversion or bile acids biosynthesis is critically regulated in order to maintain cholesterol or bile acids homeostasis in the body. (biomedcentral.com)
- Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. (nih.gov)
- The selected examples showed larger genetic effect sizes for lifestyle conditions associated with higher vis-à-vis lower average HDL-cholesterol concentrations. (nih.gov)
- These results strongly suggest that polycyclic aromatic hydrocarbons perturb the metabolism of sterol in the skin of mice while keeping the total amount of cholesterol unchanged. (lookformedical.com)
- Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. (elsevierpure.com)
- LDL + VLDL and HDL cholesterol were reduced by 56-75% and 25-41%, respectively. (nih.gov)
- These results reveal an elaborate autoregulatory cascade mediated by nuclear receptors for the maintenance of hepatic cholesterol catabolism. (nih.gov)
- Enzima del citocromo P450 unida a la membrana que cataliza la 7-alfa-hidroxilación del COLESTEROL en presencia de oxígeno molecular y NADPH-FERRIHEMOPROTEÍNA REDUCTASA. (bvsalud.org)
- Alteration of cholesterol biosynthetic pathways in the skin of mice administered polycyclic aromatic hydrocarbons. (lookformedical.com)
- Using a metabolic inhibitor, diazacholesterol, it was shown that sterols which reduce in mouse skin by administration of carcinogen and promoters were similar to those which reduce by administration of carcinogen only and are the members of one of the two cholesterol-biosynthetic pathways, i.e., a pathway which proceeds through intermediates with a saturated side chain. (lookformedical.com)
- The low cholesteryl esterase activity does not result in reduced LDL-cholesterol ester degradation in mouse fibroblasts in situ. (zhangqiaokeyan.com)
- BACKGROUND: The phenotypic expression of a high-density lipoprotein (HDL) genetic risk score has been shown to depend upon whether the phenotype (HDL-cholesterol) is high or low relative to its distribution in the population (quantile-dependent expressivity). (nih.gov)
- Cholecalciferol is formed in the human skin from 7-dehydrocholesterol (7-DHC), a cholesterol precursor, in the presence of ultraviolet B radiation (UVB). (vitamindwiki.com)
- The results (e.g., elevated acylcarnitine levels) were in agreement with previous population-based findings (6) and recovery of euthyroidism among women with Graves disease (7). (deepdyve.com)
- It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. (illumina.com)
- This suggests these reported interactions could be the result of selecting subjects for conditions that differentiate high from low HDL-cholesterol (e.g., lean vs. overweight, active vs. sedentary, high-fat vs. high-carbohydrate diets, alcohol drinkers vs. abstainers, nonsmokers vs. smokers) producing larger versus smaller genetic effect sizes. (nih.gov)
- Diaza derivative of cholesterol which acts as a hypocholesteremic agent by blocking delta-24-reductase, which causes the accumulation of desmosterol. (lookformedical.com)
- The abnormal buildup of cholesterol in the brain probably also contributes to the death of nerve cells. (medlineplus.gov)
- A dose of 300 mg aminoglutethimide phosphate, which inhibits the conversion of cholesterol to 20 alpha-hydroxycholesterol, blocked the LH-induced ovulation and prevented the normal rise in plasma progesterone. (lookformedical.com)
- These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral. (illumina.com)
- A great number of studies have revealed that taurine has cholesterol-lowering effect since Tsuji et al. (biomedcentral.com)