Download Effects of biotin on pyruvate carboxylase, acetyl CoA

Effects of biotin on pyruvate carboxylase, acetyl CoA
carboxylase, propionyl CoA 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
 3-hydroxyisovaleric acid
o Propionyl CoA Carboxylase (PCC)
o
Sensitive indicator of biotin status
Biotin and PCC, PC, and ACC
Pyruvate
Carboxylase (PC)
Propionyl-CoA
Carboxylase
(PCC)
Acetyl CoA
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 =15mg
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 CoA carboxylase, propionyl-CoA
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.