Pyridoxal 5-phosphate-dependent enzyme (PLP-dependent enzyme)

Pyridoxal 5-phosphate (PLP)-dependent enzymes are a vast superfamily of enzymes that utilize the active form of vitamin B6 as an essential cofactor to catalyze a diverse array of biochemical transformations, primarily involving amino acid metabolism (Percudani & Peracchi, 2003, PMID: 12948554). These enzymes are categorized into several distinct structural fold types and are responsible for critical processes such as transamination, decarboxylation, and deamination (Eliot & Kirsch, 2004, PMID: 14744150). They play a pivotal role in the synthesis of key neurotransmitters like dopamine, serotonin, and GABA, making them vital targets in the treatment of neurological disorders (Clayton, 2006, PMID: 16763894). For instance, DOPA decarboxylase is targeted in Parkinson's disease, while GABA transaminase is targeted in epilepsy. Beyond neurology, these enzymes are involved in heme biosynthesis, glycogen metabolism, and the regulation of homocysteine levels. Pharmacological agents often target specific members of this class through suicide inhibition or competitive binding at the active site. However, because PLP is required by over 140 different human enzymes, pharmacological interference with this cofactor can lead to significant systemic toxicity, most notably peripheral neuropathy and vitamin B6 depletion (StatPearls, NBK470579). Consequently, while they offer significant therapeutic potential, drug development must carefully manage the risks of off-target inhibition within this broad enzyme class.

Other names

Vitamin B6-dependent enzymeB6-dependent enzymePyridoxal phosphate-dependent enzyme

Drugs targeting this class typically function as irreversible suicide inhibitors of specific enzymes, competitive inhibitors at the active site, or by chemically reacting with and sequestering the PLP cofactor itself.