Pyruvate carboxylase and metabolic syndrome

Pyruvate carboxylase is a biotin-dependent enzyme involved in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitters, and in glucose-induced insulin secretion by pancreatic islets. Pyruvate carboxylase is a key to beta cell adaptation to insulin resistance where pyruvate carboxylase reduction can lead to beta cell failure. In Agouti-K mice reduction of pyruvate carboxylase in pancreatic islets could play a role in the development of Type 2 diabetes.

Biotin deficiencies both by decreasing metabolism of branched-chain amino acids and decreasing activity of pyruvate carboxylase could lead to the development of metabolic syndrome in humans. Both biotin and pantothenate would have to be taken to treat metabolic syndrome where biotin would be taken three times a day and pantothenic acid taken once a day away from biotin. Both biotin and pantothenate are transported by the the sodium-dependent multivitamin transporter (SMVT). Pantothenic acid taken alone could competitively inhibit transport of biotin by the SMVT while biotin taken alone could decrease transport of pantothenic acid by biotinylation of histones at the SMVT locus.

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