Gene Association: CBLC
UniProt Search:
CBLC (PROTEIN_CODING)
Function Description: Cbl proto-oncogene C
found 24 associated metabolites with current gene based on the text mining result from the pubmed database.
Vincamine
Vincamine is a vinca alkaloid, an alkaloid ester, an organic heteropentacyclic compound, a methyl ester and a hemiaminal. It has a role as an antihypertensive agent, a vasodilator agent and a metabolite. It is functionally related to an eburnamenine. Vincamine is a monoterpenoid indole alkaloid obtained from the leaves of *Vinca minor* with a vasodilatory property. Studies indicate that vincamine increases the regional cerebral blood flow. Vincamine is a natural product found in Vinca difformis, Vinca major, and other organisms with data available. A major alkaloid of Vinca minor L., Apocynaceae. It has been used therapeutically as a vasodilator and antihypertensive agent, particularly in cerebrovascular disorders. Vincamine. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=1617-90-9 (retrieved 2024-07-01) (CAS RN: 1617-90-9). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0). Vincamine?is a monoterpenoid indole alkaloid extracted from the?Madagascar periwinkle. Vincamine?is a peripheral?vasodilator?and exerts a selective vasoregulator action on the brain microcapilar circulation[1]. Vincamine?is a?GPR40?agonist and acts as a β-cell protector by ameliorating β-cell dysfunction and promoting glucose-stimulated insulin secretion (GSIS).?Vincamine?improves glucose homeostasis?in vivo, and has the potential for the type 2 diabetes mellitus (T2DM) research[2]. Vincamine?is a monoterpenoid indole alkaloid extracted from the?Madagascar periwinkle. Vincamine?is a peripheral?vasodilator?and exerts a selective vasoregulator action on the brain microcapilar circulation[1]. Vincamine?is a?GPR40?agonist and acts as a β-cell protector by ameliorating β-cell dysfunction and promoting glucose-stimulated insulin secretion (GSIS).?Vincamine?improves glucose homeostasis?in vivo, and has the potential for the type 2 diabetes mellitus (T2DM) research[2].
Carnitine
(R)-carnitine is the (R)-enantiomer of carnitine. It has a role as an antilipemic drug, a water-soluble vitamin (role), a nutraceutical, a nootropic agent and a Saccharomyces cerevisiae metabolite. It is a conjugate base of a (R)-carnitinium. It is an enantiomer of a (S)-carnitine. Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. L-Carnitine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). Levocarnitine is a Carnitine Analog. Levocarnitine is a natural product found in Mucidula mucida, Pseudo-nitzschia multistriata, and other organisms with data available. Levocarnitine is an amino acid derivative. Levocarnitine facilitates long-chain fatty acid entry into mitochondria, delivering substrate for oxidation and subsequent energy production. Fatty acids are utilized as an energy substrate in all tissues except the brain. (NCI04) Carnitine is not an essential amino acid; it can be synthesized in the body. However, it is so important in providing energy to muscles including the heart-that some researchers are now recommending carnitine supplements in the diet, particularly for people who do not consume much red meat, the main food source for carnitine. Carnitine has been described as a vitamin, an amino acid, or a metabimin, i.e., an essential metabolite. Like the B vitamins, carnitine contains nitrogen and is very soluble in water, and to some researchers carnitine is a vitamin (Liebovitz 1984). It was found that an animal (yellow mealworm) could not grow without carnitine in its diet. However, as it turned out, almost all other animals, including humans, do make their own carnitine; thus, it is no longer considered a vitamin. Nevertheless, in certain circumstances-such as deficiencies of methionine, lysine or vitamin C or kidney dialysis--carnitine shortages develop. Under these conditions, carnitine must be absorbed from food, and for this reason it is sometimes referred to as a metabimin or a conditionally essential metabolite. Like the other amino acids used or manufactured by the body, carnitine is an amine. But like choline, which is sometimes considered to be a B vitamin, carnitine is also an alcohol (specifically, a trimethylated carboxy-alcohol). Thus, carnitine is an unusual amino acid and has different functions than most other amino acids, which are most usually employed by the body in the construction of protein. Carnitine is an essential factor in fatty acid metabolism in mammals. Its most important known metabolic function is to transport fat into the mitochondria of muscle cells, including those in the heart, for oxidation. This is how the heart gets most of its energy. In humans, about 25\\\\\% of carnitine is synthesized in the liver, kidney and brain from the amino acids lysine and methionine. Most of the carnitine in the body comes from dietary sources such as red meat and dairy products. Inborn errors of carnitine metabolism can lead to brain deterioration like that of Reyes syndrome, gradually worsening muscle weakness, Duchenne-like muscular dystrophy and extreme muscle weakness with fat accumulation in muscles. Borurn et al. (1979) describe carnitine as an essential nutrient for pre-term babies, certain types (non-ketotic) of hypoglycemics, kidney dialysis patients, cirrhosis, and in kwashiorkor, type IV hyperlipidemia, heart muscle disease (cardiomyopathy), and propionic or organic aciduria (acid urine resulting from genetic or other anomalies). In all these conditions and the inborn errors of carnitine metabolism, carnitine is essential to life and carnitine supplements are valuable. carnitine therapy may also be useful in a wide variety of clinical conditions. carnitine supplementation has improved some patients who have angina secondary to coronary artery disease. It may be worth a trial in any form of hyperlipidemia or muscle weakness. carnitine supplements may... (-)-Carnitine. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=541-15-1 (retrieved 2024-06-29) (CAS RN: 541-15-1). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0). L-Carnitine ((R)-Carnitine), a highly polar, small zwitterion, is an essential co-factor for the mitochondrial β-oxidation pathway. L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. L-Carnitine is an antioxidant. L-Carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism[1][2][3]. L-Carnitine ((R)-Carnitine), a highly polar, small zwitterion, is an essential co-factor for the mitochondrial β-oxidation pathway. L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. L-Carnitine is an antioxidant. L-Carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism[1][2][3].
Trimethylglycine
Glycine betaine is the amino acid betaine derived from glycine. It has a role as a fundamental metabolite. It is an amino-acid betaine and a glycine derivative. It is a conjugate base of a N,N,N-trimethylglycinium. Betaine is a methyl group donor that functions in the normal metabolic cycle of methionine. It is a naturally occurring choline derivative commonly ingested through diet, with a role in regulating cellular hydration and maintaining cell function. Homocystinuria is an inherited disorder that leads to the accumulation of homocysteine in plasma and urine. Currently, no treatments are available to correct the genetic causes of homocystinuria. However, in order to normalize homocysteine levels, patients can be treated with vitamin B6 ([pyridoxine]), vitamin B12 ([cobalamin]), [folate] and specific diets. Betaine reduces plasma homocysteine levels in patients with homocystinuria. Although it is present in many food products, the levels found there are insufficient to treat this condition. The FDA and EMA have approved the product Cystadane (betaine anhydrous, oral solution) for the treatment of homocystinuria, and the EMA has approved the use of Amversio (betaine anhydrous, oral powder). Betaine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). Betaine is a Methylating Agent. The mechanism of action of betaine is as a Methylating Activity. Betaine is a modified amino acid consisting of glycine with three methyl groups that serves as a methyl donor in several metabolic pathways and is used to treat the rare genetic causes of homocystinuria. Betaine has had only limited clinical use, but has not been linked to instances of serum enzyme elevations during therapy or to clinically apparent liver injury. Betaine is a natural product found in Hypoestes phyllostachya, Barleria lupulina, and other organisms with data available. Betaine is a metabolite found in or produced by Saccharomyces cerevisiae. A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341) See also: Arnica montana Flower (part of); Betaine; panthenol (component of); Betaine; scutellaria baicalensis root (component of) ... View More ... A - Alimentary tract and metabolism > A16 - Other alimentary tract and metabolism products > A16A - Other alimentary tract and metabolism products > A16AA - Amino acids and derivatives D057847 - Lipid Regulating Agents > D000960 - Hypolipidemic Agents > D008082 - Lipotropic Agents Acquisition and generation of the data is financially supported in part by CREST/JST. D009676 - Noxae > D000963 - Antimetabolites CONFIDENCE standard compound; ML_ID 42 D005765 - Gastrointestinal Agents KEIO_ID B047
Homocysteine
A high level of blood serum homocysteine is a powerful risk factor for cardiovascular disease. Unfortunately, one study which attempted to decrease the risk by lowering homocysteine was not fruitful. This study was conducted on nearly 5000 Norwegian heart attack survivors who already had severe, late-stage heart disease. No study has yet been conducted in a preventive capacity on subjects who are in a relatively good state of health.; Elevated levels of homocysteine have been linked to increased fractures in elderly persons. The high level of homocysteine will auto-oxidize and react with reactive oxygen intermediates and damage endothelial cells and has a higher risk to form a thrombus. Homocysteine does not affect bone density. Instead, it appears that homocysteine affects collagen by interfering with the cross-linking between the collagen fibers and the tissues they reinforce. Whereas the HOPE-2 trial showed a reduction in stroke incidence, in those with stroke there is a high rate of hip fractures in the affected side. A trial with 2 homocysteine-lowering vitamins (folate and B12) in people with prior stroke, there was an 80\\\\\\% reduction in fractures, mainly hip, after 2 years. Interestingly, also here, bone density (and the number of falls) were identical in the vitamin and the placebo groups.; Homocysteine is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar (uM), even moderate hyperhomocysteinemia is associated with increased incidence of cardiovascular disease and Alzheimers disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. Pyridoxal, folic acid, riboflavin, and Vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 \\\\\\%, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionine metabolism and in determining plasma homocysteine levels is discussed. Homocysteine is an independent cardiovascular disease (CVD) risk factor modifiable by nutrition and possibly exercise. Homocysteine was first identified as an important biological compound in 1932 and linked with human disease in 1962 when elevated urinary homocysteine levels were found in children with mental retardation. This condition, called homocysteinuria, was later associated with premature occlusive CVD, even in children. These observations led to research investigating the relationship of elevated homocysteine levels and CVD in a wide variety of populations including middle age and elderly men and women with and without traditional risk factors for CVD. (PMID 17136938, 15630149); Homocysteine is an amino acid with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene (-CH2-) group. It is biosynthesized from methionine by the removal of its terminal C? methyl group. Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins.; Studies reported in 2006 have shown that giving vitamins [folic acid, B6 and B12] to reduce homocysteine levels may not quickly offer benefit, however a significant 25\\\\\\% reduction in stroke was found in the HOPE-2 study even in patients mostly with existing serious arterial decline although the overall death rate was not significantly changed by the intervention in the trial. Clearly, reducing homocysteine does not quickly repair existing... Homocysteine (CAS: 454-29-5) is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar (uM), even moderate hyperhomocysteinemia is associated with an increased incidence of cardiovascular disease and Alzheimers disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. It has been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821). Pyridoxal, folic acid, riboflavin, and vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 \\\\\\%, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionine metabolism and in determining plasma homocysteine levels is discussed. Homocysteine is an independent cardiovascular disease (CVD) risk factor modifiable by nutrition and possibly exercise. Homocysteine was first identified as an important biological compound in 1932 and linked with human disease in 1962 when elevated urinary homocysteine levels were found in children with mental retardation. This condition, called homocystinuria, was later associated with premature occlusive CVD, even in children. These observations led to research investigating the relationship of elevated homocysteine levels and CVD in a wide variety of populations including middle age and elderly men and women with and without traditional risk factors for CVD (PMID: 17136938 , 15630149). Moreover, homocysteine is found to be associated with cystathionine beta-synthase deficiency, cystathioninuria, methylenetetrahydrofolate reductase deficiency, and sulfite oxidase deficiency, which are inborn errors of metabolism. [Spectral] L-Homocysteine (exact mass = 135.0354) and L-Valine (exact mass = 117.07898) were not completely separated on HPLC under the present analytical conditions as described in AC$XXX. Additionally some of the peaks in this data contains dimers and other unidentified ions. Homocysteine is biosynthesized naturally via a multi-step process.[9] First, methionine receives an adenosine group from ATP, a reaction catalyzed by S-adenosyl-methionine synthetase, to give S-adenosyl methionine (SAM-e). SAM-e then transfers the methyl group to an acceptor molecule, (e.g., norepinephrine as an acceptor during epinephrine synthesis, DNA methyltransferase as an intermediate acceptor in the process of DNA methylation). The adenosine is then hydrolyzed to yield L-homocysteine. L-Homocysteine has two primary fates: conversion via tetrahydrofolate (THF) back into L-methionine or conversion to L-cysteine.[10] Biosynthesis of cysteine Mammals biosynthesize the amino acid cysteine via homocysteine. Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (vitamin B6) as a cofactor. Cystathionine γ-lyase then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate. Bacteria and plants rely on a different pathway to produce cysteine, relying on O-acetylserine.[11] Methionine salvage Homocysteine can be recycled into methionine. This process uses N5-methyl tetrahydrofolate as the methyl donor and cobalamin (vitamin B12)-related enzymes. More detail on these enzymes can be found in the article for methionine synthase. Other reactions of biochemical significance Homocysteine can cyclize to give homocysteine thiolactone, a five-membered heterocycle. Because of this "self-looping" reaction, homocysteine-containing peptides tend to cleave themselves by reactions generating oxidative stress.[12] Homocysteine also acts as an allosteric antagonist at Dopamine D2 receptors.[13] It has been proposed that both homocysteine and its thiolactone may have played a significant role in the appearance of life on the early Earth.[14] L-Homocysteine. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=454-28-4 (retrieved 2024-06-29) (CAS RN: 6027-13-0). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0). DL-Homocysteine is a weak neurotoxin, and can affect the production of kynurenic acid in the brain. DL-Homocysteine is a weak neurotoxin, and can affect the production of kynurenic acid in the brain. L-Homocysteine, a homocysteine metabolite, is a homocysteine that has L configuration. L-Homocysteine induces upregulation of cathepsin V that mediates vascular endothelial inflammation in hyperhomocysteinaemia[1][2].
Methylmalonyl-CoA
Methylmalonyl-CoA is an intermediate in the metabolism of Propanoate. It is a substrate for Malonyl-CoA decarboxylase (mitochondrial), Methylmalonyl-CoA mutase (mitochondrial) and Methylmalonyl-CoA epimerase (mitochondrial). [HMDB] Methylmalonyl-CoA is an intermediate in the metabolism of Propanoate. It is a substrate for Malonyl-CoA decarboxylase (mitochondrial), Methylmalonyl-CoA mutase (mitochondrial) and Methylmalonyl-CoA epimerase (mitochondrial).
Methylmalonic acid
Methylmalonic acid is a malonic acid derivative, which is a vital intermediate in the metabolism of fat and protein. In particular, the coenzyme A-linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase in a reaction that requires vitamin B12 as a cofactor. In this way, methylmalonic acid enters the Krebs cycle and is thus part of one of the anaplerotic reactions. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This inborn error of metabolism is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. Methylmalonic acid is also found to be associated with other inborn errors of metabolism, including cobalamin deficiency, cobalamin malabsorption, malonyl-CoA decarboxylase deficiency, and transcobalamin II deficiency. When present in sufficiently high levels, methylmalonic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of methylmalonic acid are associated with at least 5 inborn errors of metabolism, including Malonyl CoA decarboxylase deficiency, Malonic Aciduria, Methylmalonate Semialdehyde Dehydrogenase Deficiency, Methylmalonic Aciduria and Methylmalonic Aciduria Due to Cobalamin-Related Disorders. Methylmalonic acid is an organic acid and abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, kidney abnormalities, liver damage, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. A malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. [HMDB] KEIO_ID M014 Methylmalonic acid (Methylmalonate) is an indicator of Vitamin B-12 deficiency in cancer. Methylmalonic acid (Methylmalonate) is an indicator of Vitamin B-12 deficiency in cancer.
Dimethylbenzimidazole
Dimethylbenzimidazole is an intermediate in Riboflavin metabolism. Dimethylbenzimidazole is the second to last step for the synthesis of alpha-Ribazole. It is converted from Riboflavin then it is converted to N1-(5-Phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole via the enzyme nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21). Dimethylbenzimidazole is an intermediate in Riboflavin metabolism. KEIO_ID D087 5,6-Dimethyl-1H-benzo[d]imidazole is an endogenous metabolite.
Propionylcarnitine
D018373 - Peripheral Nervous System Agents > D018689 - Sensory System Agents An O-acylcarnitine compound having propanoyl as the acyl substituent. D002491 - Central Nervous System Agents > D000700 - Analgesics D020011 - Protective Agents > D002316 - Cardiotonic Agents D000893 - Anti-Inflammatory Agents D002317 - Cardiovascular Agents D018501 - Antirheumatic Agents
Hydroxypropionic acid
3-Hydroxypropionic acid is a carboxylic acid. It is an intermediate in the breakdown of branched-chain amino acids and propionic acid from the gut. Typically it originates from propionyl-CoA and a defect in the enzyme propionyl carboxylase. This leads to a buildup in propionyl-CoA in the mitochondria. Such a buildup can lead to a disruption of the esterified CoA:free CoA ratio and ultimately to mitochondrial toxicity. Detoxification of these metabolic end products occurs via the transfer of the propionyl moiety to carnitine-forming propionyl-carnitine, which is then transferred across the inner mitochondrial membrane. 3-Hydroxypropionic acid is then released as the free acid. As an industrial chemical, it is used in the production of various chemicals such as acrylates in industry. When present in sufficiently high levels, 3-hydroxypropionic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of hydroxypropionic acid are associated with many inborn errors of metabolism including biotinidase deficiency, malonic aciduria, methylmalonate semialdehyde dehydrogenase deficiency, methylmalonic aciduria, methylmalonic aciduria due to cobalamin-related disorders, and propionic acidemia. Hydroxypropionic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. Infants with acidosis have symptoms that include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. 3-Hydroxypropionic acid is also a microbial metabolite found in Escherichia, Klebsiella and Saccharomyces (PMID: 26360870).
Cobamamide
A member of the class of cobalamins that is vitamin B12 in which the cyano group is replaced by a 5-deoxyadenos-5-yl moiety. It is one of the two metabolically active form of vitamin B12. B - Blood and blood forming organs > B03 - Antianemic preparations > B03B - Vitamin b12 and folic acid > B03BA - Vitamin b12 (cyanocobalamin and analogues) Adenosylcobalamin (Coenzyme B12;Cobamamide;AdoCbl) is an active form of Vitamin B12 which is a cofactor for methylmalonyl CoA mutase[1] Adenosylcobalamin (Coenzyme B12;Cobamamide;AdoCbl) is an active form of Vitamin B12 which is a cofactor for methylmalonyl CoA mutase[1]
2-Methylcitric acid
Methylcitric acid (MCA) is elevated in body fluids of patients with propionic acidaemia (PA; OMIM 232000, 232050), methylmalonic aciduria (MMA; OMIM 251000, 251120) and multiple carboxylase deficiency (OMIM 253260, 253270), which are inherited disorders. MCA is formed by condensation of accumulated propionyl- CoA and oxalacetate by the enzyme si-citrate synthase (EC 4.1.3.7). MCA molecule has two stereogenic centers so that it can occur in the form of four stereoisomers. Only two stereoisomers of MCA, (2S, 3S) and (2R, 3S), were found in human urine (PMID: 17295121). Methylcitric acid (MCA) is elevated in body fluids of patients with propionic acidaemia (PA; OMIM 232000, 232050), methylmalonic aciduria (MMA; OMIM 251000, 251120) and multiple carboxylase deficiency (OMIM 253260, 253270). MCA is formed by condensation of accumulated propionyl- CoA and oxalacetate by the enzyme si-citrate synthase (EC 4.1.3.7). MCA molecule has two stereogenic centers so that it can occur in the form of four stereoisomers. Only two stereoisomers of MCA, (2S, 3S) and (2R, 3S), were found in human urine. (PMID: 17295121) [HMDB] 2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1]. 2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1]. 2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1].
5,10-Methylene-THF
5,10-Methylene-THF is an intermediate in glycine, serine and threonine metabolism and one carbon metabolism. 5,10-CH2-THF can also be used as a coenzyme in the biosynthesis of thymidine. More specifically it is the C1-donor in the reactions catalyzed by thymidylate synthase and thymidylate synthase (FAD). It also acts as a coenzyme in the synthesis of serine from glycine via the enzyme serine hydroxymethyl transferase. 5,10-Methylene-THF is a substrate for Methylenetetrahydrofolate reductase. This enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to methionine. The body uses methionine to make proteins and other important compounds. 5,10-CH2-THF is a substrate for many enzymes including Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (mitochondrial), Aminomethyltransferase (mitochondrial), Serine hydroxymethyltransferase (mitochondrial), Methylenetetrahydrofolate reductase, C-1-tetrahydrofolate synthase (cytoplasmic), Serine hydroxymethyltransferase (cytosolic) and Thymidylate synthase. 5,10-Methylene-THF is an intermediate in the metabolism of Methane and the metabolism of Nitrogen. It is a substrate for Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (mitochondrial), Aminomethyltransferase (mitochondrial), Serine hydroxymethyltransferase (mitochondrial), Methylenetetrahydrofolate reductase, C-1-tetrahydrofolate synthase (cytoplasmic), Serine hydroxymethyltransferase (cytosolic) and Thymidylate synthase. [HMDB] COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
Methylmalonic acid
A dicarboxylic acid that is malonic acid in which one of the methylene hydrogens is substituted by a methyl group. Methylmalonic acid (Methylmalonate) is an indicator of Vitamin B-12 deficiency in cancer. Methylmalonic acid (Methylmalonate) is an indicator of Vitamin B-12 deficiency in cancer.
Betaine
Betaine or trimethylglycine is a methylated derivative of glycine. It functions as a methyl donor in that it carries and donates methyl functional groups to facilitate necessary chemical processes. The donation of methyl groups is important to proper liver function, cellular replication, and detoxification reactions. Betaine also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage. Betaine has also been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th Ed, p1341). Betaine is found in many foods, some of which are potato puffs, poppy, hazelnut, and garden cress. Betaine. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=107-43-7 (retrieved 2024-06-28) (CAS RN: 107-43-7). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
Levocarnitine
Used in sport and infant nutrition. Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (or fats) for the generation of metabolic energy. It is often sold as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin Bt. Carnitine exists in two stereoisomers: its biologically active form is L-carnitine, while its enantiomer, D-carnitine, is biologically inactive.; Carnitine is not an essential amino acid; Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.; There is a close correlation between changes in plasma levels of osteocalcin and osteoblast activity and a reduction in osteocalcin plasma levels is an indicator of reduced osteoblast activity, which appears to underlie osteoporosis in elderly subjects and in postmenopausal women. Administration of a carnitine mixture or propionyl-L-carnitine is capable of increasing serum osteocalcin concentrations of animals thus treated, whereas serum osteocalcin levels tend to decrease with age in control animals.; it can be synthesized in the body. However, it is so important in providing energy to muscles including the heart-that some researchers are now recommending carnitine supplements in the diet, particularly for people who do not consume much red meat, the main food source for carnitine. Carnitine has been described as a vitamin, an amino acid, or a metabimin, i.e., an essential metabolite. Like the B vitamins, carnitine contains nitrogen and is very soluble in water, and to some researchers carnitine is a vitamin (Liebovitz 1984). It was found that an animal (yellow mealworm) could not grow without carnitine in its diet. However, as it turned out, almost all other animals, including humans, do make their own carnitine; thus, it is no longer considered a vitamin. Nevertheless, in certain circumstances-such as deficiencies of methionine, lysine or vitamin C or kidney dialysis--carnitine shortages develop. Under these conditions, carnitine must be absorbed from food, and for this reason it is sometimes referred to as a "metabimin" or a conditionally essential metabolite. Like the other amino acids used or manufactured by the body, carnitine is an amine. But like choline, which is sometimes considered to be a B vitamin, carnitine is also an alcohol (specifically, a trimethylated carboxy-alcohol). Thus, carnitine is an unusual amino acid and has different functions than most other amino acids, which are most usually employed by the body in the construction of protein. Carnitine is an essential factor in fatty acid metabolism in mammals. Its most important known metabolic function is to transport fat into the mitochondria of muscle cells, including those in the heart, for oxidation. This is how the heart gets most of its energy. In humans, about 25\\\\\%... MS2 deconvoluted using MS2Dec from all ion fragmentation data, MetaboLights identifier MTBLS1040; PHIQHXFUZVPYII_STSL_0119_Carnitine hydrochrolide_0125fmol_180430_S2_LC02_MS02_131; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. MS2 deconvoluted using CorrDec from all ion fragmentation data, MetaboLights identifier MTBLS1040; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. L-Carnitine ((R)-Carnitine), a highly polar, small zwitterion, is an essential co-factor for the mitochondrial β-oxidation pathway. L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. L-Carnitine is an antioxidant. L-Carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism[1][2][3]. L-Carnitine ((R)-Carnitine), a highly polar, small zwitterion, is an essential co-factor for the mitochondrial β-oxidation pathway. L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. L-Carnitine is an antioxidant. L-Carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism[1][2][3].
L-Homocysteine
A homocysteine that has L configuration. L-Homocysteine, a homocysteine metabolite, is a homocysteine that has L configuration. L-Homocysteine induces upregulation of cathepsin V that mediates vascular endothelial inflammation in hyperhomocysteinaemia[1][2].
Hydroxypropionic acid
A 3-hydroxy monocarboxylic acid that is propionic acid in which one of the hydrogens attached to the terminal carbon is replaced by a hydroxy group. Hydroxypropionic acid, also known as 3-hydroxypropionate or hydracrylic acid, belongs to beta hydroxy acids and derivatives class of compounds. Those are compounds containing a carboxylic acid substituted with a hydroxyl group on the C3 carbon atom. Hydroxypropionic acid is soluble (in water) and a weakly acidic compound (based on its pKa). Hydroxypropionic acid can be synthesized from propionic acid. Hydroxypropionic acid is also a parent compound for other transformation products, including but not limited to, beta-propiolactone, ascr#5, and 3-hydroxypropanoyl-CoA. Hydroxypropionic acid can be found in a number of food items such as apple, poppy, yam, and cupuaçu, which makes hydroxypropionic acid a potential biomarker for the consumption of these food products. Hydroxypropionic acid can be found primarily in blood, cerebrospinal fluid (CSF), feces, and urine. Hydroxypropionic acid exists in all living organisms, ranging from bacteria to humans. In humans, hydroxypropionic acid is involved in the propanoate metabolism. Hydroxypropionic acid is also involved in few metabolic disorders, which include malonic aciduria, malonyl-coa decarboxylase deficiency, and methylmalonic aciduria due to cobalamin-related disorders. Moreover, hydroxypropionic acid is found to be associated with biotinidase deficiency and propionic acidemia. Hydroxypropionic acid is a non-carcinogenic (not listed by IARC) potentially toxic compound. Hydroxypropanoic acid, or alternately hydroxypropionic acid, may refer to either of two isomeric chemical compounds: 3-Hydroxypropionic acid (hydracrylic acid) Lactic acid (2-hydroxypropanoic acid) . Chronically high levels of hydroxypropionic acid are associated with at least 5 inborn errors of metabolism including: Biotinidase deficiency, Malonic Aciduria, Methylmalonate Semialdehyde Dehydrogenase Deficiency, Methylmalonic Aciduria, Methylmalonic, Aciduria Due to Cobalamin-Related Disorders and Propionic acidemia (T3DB).
5,6-Dimethylbenzimidazole
A dimethylbenzimidazole carrying methyl substituents at positions 5 and 6. 5,6-Dimethyl-1H-benzo[d]imidazole is an endogenous metabolite.
Vincamin
C - Cardiovascular system > C04 - Peripheral vasodilators > C04A - Peripheral vasodilators D002317 - Cardiovascular Agents > D000959 - Antihypertensive Agents C78272 - Agent Affecting Nervous System > C47795 - CNS Stimulant D002317 - Cardiovascular Agents > D014665 - Vasodilator Agents D000970 - Antineoplastic Agents > D014748 - Vinca Alkaloids CONFIDENCE Reference Standard (Level 1); INTERNAL_ID 2327 Vincamine?is a monoterpenoid indole alkaloid extracted from the?Madagascar periwinkle. Vincamine?is a peripheral?vasodilator?and exerts a selective vasoregulator action on the brain microcapilar circulation[1]. Vincamine?is a?GPR40?agonist and acts as a β-cell protector by ameliorating β-cell dysfunction and promoting glucose-stimulated insulin secretion (GSIS).?Vincamine?improves glucose homeostasis?in vivo, and has the potential for the type 2 diabetes mellitus (T2DM) research[2]. Vincamine?is a monoterpenoid indole alkaloid extracted from the?Madagascar periwinkle. Vincamine?is a peripheral?vasodilator?and exerts a selective vasoregulator action on the brain microcapilar circulation[1]. Vincamine?is a?GPR40?agonist and acts as a β-cell protector by ameliorating β-cell dysfunction and promoting glucose-stimulated insulin secretion (GSIS).?Vincamine?improves glucose homeostasis?in vivo, and has the potential for the type 2 diabetes mellitus (T2DM) research[2].
CAR 3:0
D018373 - Peripheral Nervous System Agents > D018689 - Sensory System Agents D002491 - Central Nervous System Agents > D000700 - Analgesics D020011 - Protective Agents > D002316 - Cardiotonic Agents D000893 - Anti-Inflammatory Agents D002317 - Cardiovascular Agents D018501 - Antirheumatic Agents
Trimethylglycine
Glycine betaine is the amino acid betaine derived from glycine. It has a role as a fundamental metabolite. It is an amino-acid betaine and a glycine derivative. It is a conjugate base of a N,N,N-trimethylglycinium. Betaine is a methyl group donor that functions in the normal metabolic cycle of methionine. It is a naturally occurring choline derivative commonly ingested through diet, with a role in regulating cellular hydration and maintaining cell function. Homocystinuria is an inherited disorder that leads to the accumulation of homocysteine in plasma and urine. Currently, no treatments are available to correct the genetic causes of homocystinuria. However, in order to normalize homocysteine levels, patients can be treated with vitamin B6 ([pyridoxine]), vitamin B12 ([cobalamin]), [folate] and specific diets. Betaine reduces plasma homocysteine levels in patients with homocystinuria. Although it is present in many food products, the levels found there are insufficient to treat this condition. The FDA and EMA have approved the product Cystadane (betaine anhydrous, oral solution) for the treatment of homocystinuria, and the EMA has approved the use of Amversio (betaine anhydrous, oral powder). Betaine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). Betaine is a Methylating Agent. The mechanism of action of betaine is as a Methylating Activity. Betaine is a modified amino acid consisting of glycine with three methyl groups that serves as a methyl donor in several metabolic pathways and is used to treat the rare genetic causes of homocystinuria. Betaine has had only limited clinical use, but has not been linked to instances of serum enzyme elevations during therapy or to clinically apparent liver injury. Betaine is a natural product found in Hypoestes phyllostachya, Barleria lupulina, and other organisms with data available. Betaine is a metabolite found in or produced by Saccharomyces cerevisiae. A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341) See also: Arnica montana Flower (part of); Betaine; panthenol (component of); Betaine; scutellaria baicalensis root (component of) ... View More ... A - Alimentary tract and metabolism > A16 - Other alimentary tract and metabolism products > A16A - Other alimentary tract and metabolism products > A16AA - Amino acids and derivatives D057847 - Lipid Regulating Agents > D000960 - Hypolipidemic Agents > D008082 - Lipotropic Agents The amino acid betaine derived from glycine. D009676 - Noxae > D000963 - Antimetabolites D005765 - Gastrointestinal Agents
2-Methylcitric acid
2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1]. 2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1]. 2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate[1].
