B6-dependent aminotransferases (PLP-ATs) (PLP-ATs)

B6-dependent aminotransferases, also known as pyridoxal 5'-phosphate (PLP)-dependent aminotransferases or transaminases, are a large family of enzymes that utilize the active form of vitamin B6 as a cofactor to catalyze the transfer of amino groups between amino acids and oxoacids. This class of enzymes is central to nitrogen metabolism, amino acid biosynthesis, and the regulation of key neurotransmitters such as gamma-aminobutyric acid (GABA) and glutamate. Prominent members include GABA aminotransferase (GABA-T), a target for antiepileptic drugs, and alanine and aspartate aminotransferases (ALT and AST), which serve as vital clinical biomarkers for liver and heart health. Drugs like Vigabatrin act as mechanism-based inhibitors of specific aminotransferases, while others like isoniazid can non-selectively interfere with multiple B6-dependent processes by depleting the PLP cofactor. Therapeutic intervention in this enzyme class is used to treat epilepsy, metabolic disorders, and potentially cancer, but must be carefully managed to avoid systemic vitamin B6 deficiency and associated neurological side effects. Notable safety concerns include peripheral neuropathy and, in the case of Vigabatrin, permanent visual field defects.

Other names

AminotransferasesTransaminasesPyridoxal 5'-phosphate-dependent aminotransferasesVitamin B6-dependent aminotransferasesPLP-dependent aminotransferases

Mechanism-based irreversible inhibition (suicide inhibition), competitive inhibition, or indirect inhibition via sequestration and depletion of the essential pyridoxal 5'-phosphate (PLP) cofactor.