Structure, expression, and function of kynurenine aminotransferases in human and rodent brains

• Published in: Cellular and molecular life sciences : CMLS Vol. 67; no. 3; pp. 353 - 368
• Main Authors: Han, Qian, Cai, Tao, Tagle, Danilo A, Li, Jianyong
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01.02.2010; SP Birkhäuser Verlag Basel; Springer Nature B.V
• Subjects: Acetylcholine receptors (nicotinic); Alzheimer disease; Alzheimer's disease; Amino Acid Sequence; Amino acids; Animals; antagonists; Aspartate aminotransferase; aspartate transaminase; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain - enzymology; Catalysis; catalytic activity; Catalytic Domain; Cell Biology; Cellular biology; Chemical synthesis; cholinergic receptors; Conjugates; Cysteine; Enzymatic activity; Enzyme activity; Enzymes; Gene expression; genes; Glutamate receptors; Glutamine; Humans; Kynurenic acid; Kynurenic Acid - metabolism; kynurenine; Life Sciences; Mental disorders; Mice; Molecular biology; N-Methyl-D-aspartic acid receptors; Neurodegenerative diseases; Neurological diseases; pathophysiology; Protein structure; Protein Structure, Tertiary; Review; rodents; Schizophrenia; Structure-function relationships; Subgroups; Tertiary structure; Transaminase; Transaminases; Transaminases - chemistry; Transaminases - genetics; Transaminases - physiology; Kynurenine aminotransferase; Tryptophan metabolism; Neurodegeneration; Kynurenine; Pyridoxal 5′-phosphate; Cysteine conjugate beta-lyase; Kynurenic acid; Aminotransferase
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-009-0166-4

Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-d-aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup Iε. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.