Gene Association: ADHFE1
UniProt Search:
ADHFE1 (PROTEIN_CODING)
Function Description: alcohol dehydrogenase iron containing 1
found 16 associated metabolites with current gene based on the text mining result from the pubmed database.
temephos
D010575 - Pesticides > D007306 - Insecticides D016573 - Agrochemicals
Succinic acid semialdehyde
Succinic acid semialdehyde (or succinate semialdehyde) is an intermediate in the catabolism of gamma-aminobutyrate or GABA (PMID:16435183). It is formed from GABA by the action of GABA transaminase, which leads to the production of succinate semialdehyde and alanine. The resulting succinate semialdehyde is further oxidized by succinate semialdehyde dehydrogenase to become succinic acid, which also yields NADPH. Under certain situations, high levels of succinate semialdehyde can function as a neurotoxin and a metabotoxin. A neurotoxin is a compound that causes damage to the brain and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Elevated serum levels of succinate semialdehyde are found in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria), a rare neurometabolic disorder of gamma-aminobutyric acid (GABA) degradation. Symptoms include motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Patients also exhibit behavioural problems such as attention deficit, hyperactivity, anxiety, or aggression (PMID:18622364). Succinate semialdehyde is considered a reactive carbonyl and may lead to increased oxidative stress. This stress is believed to contribute to the formation of free radicals in the brain tissue of animal models induced with SSADH deficiency, which further leads to secondary cell damage and death. Additionally, oxidative stress may be responsible for the loss of striatal dopamine, which may contribute to the neuropathology of SSADH deficiency. Succinic acid semialdehyde is an intermediate in the catabolism of gamma-aminobutyrate (PMID 16435183). Succinate semialdehyde dehydrogenase is an enzyme that catalyses the reaction of succinate semialdehyde and NAD+ to form succinate and NADH. Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. Symptoms include motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Patients also exhibit behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression. (PMID: 18622364) [HMDB]. Succinic acid semialdehyde is found in many foods, some of which are yellow zucchini, japanese chestnut, banana, and pineappple sage.
D-2-Hydroxyglutaric acid
In humans, D-2-hydroxyglutaric acid is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria it is formed by a 2-hydroxyglutarate synthase. D-2-Hydroxyglutaric acid is also formed via the normal activity of hydroxyacid-oxoacid transhydrogenase during conversion of 4-hydroxybutyrate to succinate semialdehyde. The compound can be converted to alpha-ketoglutaric acid through the action of a 2-hydroxyglutarate dehydrogenase (EC 1.1.99.2). In humans, there are two such enzymes (D2HGDH and L2HGDH). Both the D and the L stereoisomers of hydroxyglutaric acid are found in body fluids. D-2-Hydroxyglutaric acid is a biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria (OMIM: 600721) and the genetic disorder glutaric aciduria II. D-2-Hydroxyglutaric aciduria (caused by loss of D2HGDH or gain of function of IDH) is rare, with symptoms including cancer, macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. An elevated urine level of D-2-hydroxyglutaric acid has been reported in patients with spondyloenchondrodysplasia (OMIM: 271550). D-2-Hydroxyglutaric acid can be converted to alpha-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (D2HGDH). Additionally, the enzyme D-3-phosphoglycerate dehydrogenase (PHGDH) can catalyze the NADH-dependent reduction of alpha-ketoglutarate (AKG) to D-2-hydroxyglutarate (D-2HG). Nyhan et al. (1995) described 3 female patients, 2 of them sibs, who were found to have excess accumulation of D-2-hydroxyglutaric acid in the urine. The phenotype was quite variable, even among the sibs, but included mental retardation, macrocephaly with cerebral atrophy, hypotonia, seizures, and involuntary movements. One of the patients developed severe intermittent vomiting and was given a pyloromyotomy. The electroencephalogram demonstrated hypsarrhythmia. There was an increased concentration of protein in cerebrospinal fluid, an unusual finding in inborn errors of metabolism. D-2-Hydroxyglutaric acid can also be produced via gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of the TCA cycle and this compound is generated in high abundance when IDH is mutated. Since D-2-hydroxyglutaric acid is sufficiently similar in structure to 2-oxoglutarate (2OG), it is able to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and members of the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This inhibitory effect leads to alterations in the hypoxia-inducible factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that D-2-hydroxyglutaric acid causes a cascading effect that leads genetic perturbations and malignant transformation. Depending on the circumstances, D-2-hydroxyglutaric acid can act as an oncometabolite, a neurotoxin, an acidogen, and a metabotoxin. An oncometabolite is a compound that promotes tumour growth and survival. A neurotoxin is compound that is toxic to neurons or nerual tissue. 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. As an oncometabolite, D-2-hydroxyglutaric acid is a competitive inhibitor of multiple alpha-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5mC hydroxylases. As a result, high levels of 2-hydroxyglutarate lead to genome-wide histone and DNA methylation alterations, which in turn lead to mutations that ultimately cause cancer (PMID: 29038145). As a neurotoxin, D-2-hydroxyglutaric acid mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. D-2-Hydroxyglutaric acid is structurally similar to the excitatory amino acid glutamate and stimul... Tissue accumulation of high amounts of D 2 hydroxyglutaric acid is the biochemical hallmark of the inherited neurometabolic disorder D 2 hydroxyglutaric aciduria.
4-Hydroxybutyric acid
4-Hydroxybutyric acid (also known as gamma-hydroxybutyrate or GHB) is a precursor and a metabolite of gamma-aminobutyric acid (GABA). GHB acts as a central nervous system (CNS) neuromodulator, mediating its effects through GABA and GHB-specific receptors, or by affecting dopamine transmission (PMID: 16620539). GHB occurs naturally in all mammals, but its function remains unknown. GHB is labeled as an illegal drug in most countries, but it also is used as a legal drug (Xyrem) in patients with narcolepsy. It is used illegally (under the street names juice, liquid ecstasy, or G) as an intoxicant for increasing athletic performance and as a date rape drug. In high doses, GHB inhibits the CNS, inducing sleep and inhibiting the respiratory drive. In lower doses, its euphoriant effect predominates (PMID: 17658710). When present in sufficiently high levels, 4-hydroxybutyric acid can act as an acidogen, a neurotoxin, and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A neurotoxin is a compound that adversely affects neural cells and tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of 4-hydroxybutyric acid are associated with two inborn errors of metabolism: glutaric aciduria II and succinic semialdehyde dehydrogenase deficiency (SSADH). SSADH deficiency leads to a 30-fold increase of GHB and a 2-4 fold increase of GABA in the brains of patients with SSADH deficiency as compared to normal brain concentrations of the compounds. As an acidogen, 4-hydroxybutyric 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. Many affected children with organic acidemias experience intellectual disability or delayed development. These are also the characteristic symptoms of the untreated IEMs mentioned above. Particularly for SSADH deficiency, the most common features observed include developmental delay, hypotonia, and intellectual disability. Nearly half of patients exhibit ataxia, seizures, behaviour problems, and hyporeflexia. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. As a neurotoxin, GHB appears to affect both GABA (a neurotransmitter) signaling and glutamate signaling (another neurotransmitter). Glutamine metabolism may also play a role in the pathophysiology of excessive levels of GHB. High levels of GHB have been shown to depress both the NMDA and AMPA/kainite receptor-mediated functions and may also alter glutamatergic excitatory synaptic transmission as well. 4-Hydroxybutyric acid is a microbial metabolite found in Aeromonas, Escherichia and Pseudomonas (PMID: 19434404). 4-hydroxybutyric acid may cause bradycardia and dyskinesias.
2-Oxoadipic acid
2-Oxoadipic acid is produced from lysine in the cytosol of cells via the saccharopine and the pipecolic acid pathways. Catabolites of hydroxylysine and tryptophan enter these pathways as 2-aminoadipic- -semialdehyde and 2-oxoadipate, respectively. In the matrix of mitochondria, 2-oxoadipate is decarboxylated to glutaryl-CoA by the 2-oxoadipate dehydrogenase complex and then converted to acetyl-CoA. 2-Oxoadipic aciduria is an in-born error of metabolism of lysine, tryptophan, and hydroxylysine, in which abnormal quantities of 2-aminoadipic acid are found in body fluids along with 2-oxoadipic acid. Patients with 2-Oxoadipic acidemias are mentally retarded with hypotonia or seizures. 2-Oxoadipic aciduria can occur in patients with Kearns-Sayre Syndrome, a progressive disorder with onset prior to 20 years of age in which multiple organ systems are affected, including progressive external ophthalmoplegia, retinopathy, and the age of onset, and these are associated classically with abnormalities in cardiac conduction, cerebellar signs, and elevated cerebrospinal fluid protein (PMID: 10655159, 16183823, 11083877). Oxoadipic acid is found to be associated with alpha-aminoadipic aciduria, which is an inborn error of metabolism. Present in pea seedlings KEIO_ID K009 Oxoadipic acid is a key metabolite of the essential amino acids tryptophan and lysine.
Allyl alcohol
Allyl alcohol is found in onion-family vegetables. Allyl alcohol is present in garlic (Allium sativum).Allyl alcohol is an organic compound with the structural formula CH2=CHCH2OH. Like many alcohols, it is a water soluble, colourless liquid, but it is more toxic than typical small alcohols. Allyl alcohol is used as a raw material for the production of glycerol, but is used as a precursor to many specialized compounds. Allyl alcohol is the smallest representative of the allylic alcohols. (Wikipedia Present in garlic (Allium sativum)
2-Hydroxyglutarate
2-Hydroxyglutarate exists in 2 isomers: L-2-hydroxyglutarate acid and D-2-hydroxyglutarate. Both the D and the L stereoisomers of hydroxyglutaric acid (EC 1.1.99.2) are found in body fluids. In humans it is part of butanoate metabolic pathway and can be produced by phosphoglycerate dehydrogenase (PHGDH). More specifically, the enzyme PHGDH catalyzes the NADH-dependent reduction of ?-ketoglutarate (AKG) to D-2-hydroxyglutarate (D-2HG). 2-hydroxyglutarate is also the product of gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). Additionally, 2-hydroxyglutarate can be converted to ?-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (HGDH). Humans have to variants of this enzyme: D-2-hydroxyglutarate dehydrogenase (D2HGDH) and L-2-hydroxyglutarate dehydrogenase (L2HGDH). A deficiency in either of these two enzymes can lead to a disease known as 2-hydroxyglutaric aciduria. L-2-hydroxyglutaric aciduria (caused by loss of L2HGDH) is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression. D-2-hydroxyglutaric aciduria (caused by loss of D2HGDH or gain of function of IDH) is rare, with symptoms including cancer, macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. 2-hydroxyglutarate was the first oncometabolite (or cancer-causing metabolite) to be formally named or identified. In cancer it is either produced by overexpression of phosphoglycerate dehydrogenase (PHGDH) or is produced in excess by gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of TCA cycle and is generated in high abundance when IDH is mutated. 2-hydroxyglutarate is sufficiently similar in structure to 2-oxogluratate (2OG) that it is able to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and members of the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This inhibitory effect leads to alterations in the hypoxia induced factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that 2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation. Furthermore, 2-hydroxyglutarate is found to be associated with glutaric aciduria II, which is also an inborn error of metabolism. 2-Hydroxyglutarate has also been found to be a metabolite in Aspergillus (PMID: 6057807).
2-hydroxyglutaric acid
A 2-hydroxydicarboxylic acid that is glutaric acid in which one hydrogen alpha- to a carboxylic acid group is substituted by a hydroxy group.
4-Hydroxybutyric acid
A 4-hydroxy monocarboxylic acid that is butyric acid in which one of the hydrogens at position 4 is replaced by a hydroxy group.
Oxoadipic acid
An oxo dicarboxylic acid that is adipic acid substituted by an oxo group at position 2. Oxoadipic acid is a key metabolite of the essential amino acids tryptophan and lysine.
temephos
D010575 - Pesticides > D007306 - Insecticides D016573 - Agrochemicals
ALLYL ALCOHOL
A propenol in which the C=C bond connects C-2 and C-3. It is has been found in garlic (Allium sativum). Formerly used as a herbicide for the control of various grass and weed seeds.
