Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P) is a coenzyme, the active form of vitamin B6. Pyridoxal 5′-phosphate (PLP) is used as a cofactor for a wide range of enzymes including mitochondrial cysteine desulfurase, cystathionine γ-synthase (CGS), ornithine 4,5-aminomutase (OAM), and d-serine dehydratase. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates. PLP acts as a coenzyme in all transamination reactions, in various beta-elimination reactions, in the condensation reaction in heme synthesis.

Alpha-ketoglutarate (AKG), an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. As an intermediate of the tricarboxylic acid cycle, AKG is essential for the oxidation of fatty acids, amino acids, and glucose. Extracellular AKG is a significant source of energy for cells of the gastrointestinal tract. As a precursor for the synthesis of glutamate and glutamine in multiple tissues (including liver, skeletal muscle, heart, brain, and white adipose tissue), AKG bridges carbohydrate and nitrogen metabolism for both conservation of amino acids and ammonia detoxification. Additionally, emerging evidence shows that AKG is a regulator of gene expression and cell signaling pathways (including the mammalian target of rapamycin and AMPactivated protein kinase). Thus, AKG is an attractive dietary supplement in animal and human nutrition to improve cellular energy status, immunity, and health.AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. Orally, AKG is used for kidney disease, gastrointestinal disorders, bacterial overgrowth, intestinal toxemia, liver dysfunction, and chronic candidiasis. It is also used for improving peak athletic performance, improving amino acid metabolism in hemodialysis patients, and cataracts. Intravenously, AKG is used for preventing ischemic injury during heart surgery, improving renal blood flow after heart surgery, and preventing muscle protein depletion after surgery or trauma.