Branched-chain amino acid degradation, beta-oxidation and biotin

On this blog I have argued that the sodium-dependent multivitamin transporter (SMVT) is dysregulated in bipolar depression. . The SMVT transports biotin. Biotin-dependent enzymes, methylcrotonoyl-CoA carboxylase and propionyl-CoA carboxylase are involved in the degradation of branched-chain amino acids.. Methylcrotonoyl-CoA carboxylase and propionyl-CoA carboxylase in the branched-chain amino acid pathway are very closely associated with enzymes that are also involved in beta-oxidation.

Enoyl-CoA hydratase is involved in both the degradation of branched-chain amino acids and beta-oxidation. 3-hydroxyacyl-CoA dehydrogenase is involved in both the degradation of branched-chain amino acids and beta-oxidation. Acetyl-CoA acyltransferase is involved in both the degradation of branched-chain amino acids and beta-oxidation. Acyl-Coenzyme A dehydrogenase is an enzyme involved in both the degradation of branched-chain amino acids and beta-oxidation. These four enzymes are one on two enzymes away from biotin-dependent enzymes in the branched-chain amino acid degradation pathway.

The upshot of this in that dysregulation of biotin-dependent enzymes in the branched-chain amino acid degradation pathway will also dysregulate the beta-oxidation pathway. In conjunction with other supplements olive oil, which will increase beta-oxidation, can be a helpful supplement.

Insulin resistance and elevated levels of circulating branched-chain amino acids

Elevated circulating levels of branched-chain amino acids have been associated with insulin resistance where decreased degradation of branched-chain amino acids could be what is leading to elevated circulating levels of branched-chain amino acids. Metabolic syndrome is associated with insulin resistance.

Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase are two biotin-dependent enzymes in the branched-chain amino acid degradation pathway. Dysregulation of the sodium-dependent multivitamin transporter which transports biotin could dysregulate the branched-chain amino acid degradation pathway leading to high levels of circulating branched-chain amino acids and insulin resistance.

Insulin resistance is present in 52% of individuals with bipolar disorder. Insulin resistance develops is brains of individuals with Alzheimer’s disease. In China in individuals with schizophrenia the prevalence of insulin resistance is 37.2% Both disease processes and drugs used to treat these illnesses could increase insulin resistance in theses illnesses. A commonality among these illnesses could be dysregulation of the sodium-dependent multivitamin transporter both by disease processes and drugs used to treat these illnesses.

Biotin supplementation decreases hyperglycemia, normalizing glucose levels, in patients with non-insulin dependent diabetes. There is reduced hyperglycemia is diabetic patients taking biotin.

The sodium-dependent multivitamin transporter transports both biotin and pantothenate. Pantothenate is needed to synthesize coenzyme A which is closely tied to the actions of biotin-dependent enzymes. Biotinylation of the sodium-dependent transporter reduces transport by the sodium-dependent multivitamin transporter. High levels of biotin could decrease transport of pantothenate by the sodium-dependent multivitamin transporter. A combination of pantothenic acid and biotin where 500 mg. of pantothenic acid is taken once a day away from supplemental biotin and 5 mg of biotin is taken three times a day could word work better in controlling hyperglycemia than biotin alone.

Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) can distinguish between biotin-deficient and biotin-sufficient individuals. Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase could be particularly sensitive to biotin deficiencies.