Effects of biotin on pyruvate carboxylase acetyl Co

Effects of biotin on pyruvate carboxylase, acetyl Co. A carboxylase, propionyl Co. A carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects. Lisolet Avila Sarah Tobin

Biotin �Decreased biotin status is observed in: Pregnancy Elderly Athletes Type 2 Diabetics �Assessment of biotin status o 3 -hydroxyisovaleric acid Propionyl Co. A Carboxylase (PCC) o Sensitive indicator of biotin status

Biotin and PCC, PC, and ACC Pyruvate Carboxylase (PC) Propionyl-Co. A Carboxylase (PCC) Acetyl Co. A Carboxylase (ACC)

Purpose • To determine the biotin effects on the carboxylase activities, and the plasma metabolites in type 2 diabetic and nondiabetic subjects.

Methods � Mexican study � Subjects: 39 patients (20 women, 19 men) of type 2 DM, aged 33 -70 years old � Control group: 42 nondiabetic subjects (29 women, 13 men), aged 30 -60 years old � Two protocols Venous blood samples after an overnight 12 h fast � On days 0, 14 and 28. Double blind placebo control study � Either placebo or 20. 5 µmol biotin 3 times/day =15 mg

Results �Carboxylase activities at baseline No difference between diabetic and nondiabetic subjects. No significant correlation between fasting glucose concentrations and the activities of PCC, AC and ACC.

Results �Effect of biotin administration on carboxylases Increased enzymatic activity in all the carboxylases after administration of 61. 4 µmol/d for 28 days.

Results �Effect of biotin administration on plasma metabolites Biotin treatment showed not effect on fasting glucose, insulin, triacylglycerols, cholesterol or lactate concentrations. Both diabetic and nondiabetic subjects showed same results. Placebo did not alter any result.

Author’s conclusions �No direct correlation between PCC activity and fasting glucose concentrations �PC and ACC activity did not differ significantly between diabetic and nondiabetic subjects. �Biotin treatment increases PCC activity in both malnourished and subject with no nutrition deficiencies. �PC and ACC activity increases with biotin treatment. �PC activity was more sensitive to biotin supplementation that PCC and ACC.

Our Thoughts… �Limitations Genetic and nutritional differences between Mexican and other populations. Japanese study showed much different results. Cross-sectional study is needed. Diet Regulation

Our Thoughts… Expected Results: � Biotin increases PCC, PC, and ACC activity This is expected because biotin is a cofactor Unexpected Results � PC and ACC activity: same in diabetic and nondiabetic? Diabetic patients have been shown to have a lower serum biotin concentration than control groups. With biotin treatment, diabetic subjects should have a higher activity? � Biotin treatment increases PCC in subjects who are malnourished as well as those with no nutritional deficiencies Increased enzymatic activity, even in those with a sufficient diet

More Thoughts… � PC activity more sensitive to biotin than PCC and ACC This result is different than other studies which have shown that PCC activity is a sensitive indicator of serum biotin concentration. � PCC Activity and fasting glucose concentrations Carboxylase and glucose concentrations = no correlation Past studies have shown that biotin induces insulin secretion, glucokinase, and downregulates PEPCK expression in biotin deficient rats.

Question! �What are the possible metabolic outcomes observed in biotin deficient individuals? Hint: Outcome from PC, ACC, PCC and MCC Answer: Lactic Acidosis, Ketosis, Accumulation of Metabolites: ie. 3 -hydroxyisovaleric

Reference 1)Baez-Saldana A, Cardenas A, Fernandez-Mejia C, Islas-Andrade S, Revilla-Monsalve C, Rojas-Ochoa A and Zendejas-Ruiz I. Effects of biotin on pyruvate carboxylase, acetyl Co. A carboxylase, propionyl-Co. A carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects. 2004 American Journal of Clinical Nutrition. 2004; 79: 238 -243.