Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated −NH+
3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.
Isocitrate dehydrogenase (IDH) (EC 1.1.1.42) and (EC 1.1.1.41) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome.
Glutaric acidemia type 1 (GA1) is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products can accumulate and cause damage to the brain, but particularly the basal ganglia, which are regions that help regulate movement. GA1 causes secondary carnitine deficiency, as glutaric acid, like other organic acids, is detoxified by carnitine. Mental retardation may occur.
2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine. It is either autosomal recessive or autosomal dominant.
Glutaryl-CoA dehydrogenase (GCDH) is an enzyme encoded by the GCDH gene on chromosome 19. The protein belongs to the acyl-CoA dehydrogenase family (ACD). It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and carbon dioxide in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants.
3-Methylglutaconyl-CoA hydratase, also known as MG-CoA hydratase and AUH, is an enzyme encoded by the AUH gene on chromosome 19. It is a member of the enoyl-CoA hydratase/isomerase superfamily, but it is the only member of that family that is able to bind to RNA. Not only does it bind to RNA, AUH has also been observed to be involved in the metabolic enzymatic activity, making it a dual-role protein. Mutations of this gene have been found to cause a disease called 3-Methylglutaconic Acuduria Type 1.
Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial is an enzyme that in humans is encoded by the DBT gene.
Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial is an enzyme that in humans is encoded by the DLST gene.
Ganglioside-induced differentiation-associated protein 1 is a type of protein that in humans is encoded by the GDAP1 gene.
Phosphoglycerate dehydrogenase (PHGDH) is an enzyme that catalyzes the chemical reactions
The human ETFB gene encodes the Electron-transfer-flavoprotein, beta subunit, also known as ETF-β. Together with Electron-transfer-flavoprotein, alpha subunit, encoded by the 'ETFA' gene, it forms the heterodimeric Electron transfer flavoprotein (ETF). The native ETF protein contains one molecule of FAD and one molecule of AMP, respectively.
Branched chain ketoacid dehydrogenase kinase (BCKDK) is an enzyme encoded by the BCKDK gene on chromosome 16. This enzyme is part of the mitochondrial protein kinases family and it is a regulator of the valine, leucine, and isoleucine catabolic pathways. BCKDK is found in the mitochondrial matrix and the prevalence of it depends on the type of cell. Liver cells tend to have the lowest concentration of BCKDK, whereas skeletal muscle cells have the highest amount. Abnormal activity of this enzyme often leads to diseases such as maple syrup urine disease and cachexia.
L-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the L2HGDH gene, also known as C14orf160, on chromosome 14.
Alpha-aminoadipic semialdehyde synthase is an enzyme encoded by the AASS gene in humans and is involved in their major lysine degradation pathway. It is similar to the separate enzymes coded for by the LYS1 and LYS9 genes in yeast, and related to, although not similar in structure, the bifunctional enzyme found in plants. In humans, mutations in the AASS gene, and the corresponding alpha-aminoadipic semialdehyde synthase enzyme are associated with familial hyperlysinemia. This condition is inherited in an autosomal recessive pattern and is not considered a particularly negative condition, thus making it a rare disease.
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial is an enzyme that in humans is encoded by the ETFDH gene. This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain.
Hydroxyacyl-Coenzyme A dehydrogenase (HADH) is an enzyme which in humans is encoded by the HADH gene.
Aldehyde dehydrogenase 7 family, member A1, also known as ALDH7A1 or antiquitin, is an enzyme that in humans is encoded by the ALDH7A1 gene. The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified.
F-box and leucine-rich repeat protein 4 is a protein that in humans is encoded by the FBXL4 gene.
Alpha-aminoadipic and alpha-ketoadipic aciduria is an autosomal recessive metabolic disorder characterized by an increased urinary excretion of alpha-ketoadipic acid and alpha-aminoadipic acid. It is caused by mutations in DHTKD1, which encodes the E1 subunit of the oxoglutarate dehydrogenase complex.
Succinate dehydrogenase complex assembly factor 1 (SDHAF1), also known as LYR motif-containing protein 8 (LYRM8), is a protein that in humans is encoded by the SDHAF1, or LYRM8, gene. SDHAF1 is a chaperone protein involved in the assembly of the succinate dehydrogenase (SDH) complex. Mutations in this gene are associated with SDH-defective infantile leukoencephalopathy and mitochondrial complex II deficiency.
