Pyridoxal 5'-phosphate-dependent aminotransferase (PLP-dependent aminotransferase)

Pyridoxal 5'-phosphate (PLP)-dependent aminotransferases are a diverse family of enzymes that catalyze the transfer of an amino group from an amino acid to an alpha-keto acid, utilizing the active form of Vitamin B6 (PLP) as an essential cofactor [1]. These enzymes are fundamental to cellular metabolism, playing critical roles in the synthesis and degradation of amino acids, nitrogen shuttling, and the regulation of key neurotransmitters such as gamma-aminobutyric acid (GABA) [1,2]. In clinical practice, specific aminotransferases like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serve as vital biomarkers for liver injury [4]. From a therapeutic perspective, this enzyme class is targeted to treat various conditions; for example, vigabatrin acts as a suicide inhibitor of GABA aminotransferase to increase inhibitory neurotransmission in epilepsy [2]. Furthermore, research has identified branched-chain aminotransferases (BCAT1) as significant drivers in certain cancers, such as glioblastoma and leukemia, positioning them as emerging targets for oncology drug development [3]. Despite their therapeutic potential, the high structural conservation of the PLP-binding site across the proteome presents challenges for drug selectivity, often leading to side effects related to B6 depletion or neurological toxicity [1,2]. Sources: [1] Eliot AC, Kirsch JF. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu Rev Biochem. 2004;73:383-415. [2] StatPearls. Vigabatrin. https://www.ncbi.nlm.nih.gov/books/NBK557433/ [3] Tonjes M, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Commun. 2013;4:1567. [4] StatPearls. Liver Function Tests. https://www.ncbi.nlm.nih.gov/books/NBK482489/

Other names

TransaminasePLP-dependent enzymeAminotransferaseB6-dependent aminotransferase4-aminobutyrate aminotransferaseAlanine aminotransferaseAspartate aminotransferase

Irreversible suicide inhibition of the enzyme active site, competitive inhibition of substrate binding, and depletion of the essential pyridoxal 5'-phosphate cofactor.