Hypoglycemia due to Biotin deficiency?

A 32-year-old body builder has decided to go on a diet consisting of egg whites to ensure only proteins for muscle growth. After a few weeks he experiences decreased energy and is found to be hypoglycemic. A nutritionist tells the patient that he most likely has the deficiency of vitamin Biotin. Which of the following enzymes is unable to catalyze its step in synthesizing glucose from pyruvate?

A) Pyruvate carboxylase

B) Phospho enol pyruvate carboxy kinase

C) Glucose-6-phosphatase

D) Fructose 1, 6 bisphosphatase

E) Phosphoglycerate kinase.

The correct answer is- A) – Pyruvate carboxylase.

Biotin deficiency is very common in bodybuilders, who consume raw egg whites. The Raw egg whites contain Avidin, a glycoprotein that strongly binds with biotin and prevents its absorption. Once a biotin-Avidin complex forms, the bond is essentially irreversible; the biotin-Avidin complex is not broken during passage of the food bolus through the stomach and intestines. As a result, biotin is not liberated from food, and the biotin-Avidin complex is lost in the feces. Thus, the ingestion of large quantities of raw egg white over a long period can result in a biotin deficiency. Cooking egg white denatures Avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin.

Biotin functions to transfer carbon dioxide in a small number of carboxylation reactions. Biotin is attached at the active site of carboxylases.

Each Biotin dependent carboxylase catalyzes an essential metabolic reaction:

1) Pyruvate carboxylase

Pyruvate carboxylase is a critical enzyme in gluconeogenesis—the formation of glucose from sources other than carbohydrates, for example, amino acids. Oxaloacetate formed from pyruvate can be utilized in many other ways depending upon the need of the cell (Figure-3)


Reaction catalyzed by pyruvate carboxylase

Figure-1 -Carboxylation of pyruvate to Oxaloacetate, catalyzed by Pyruvate carboxylase, is the first step of gluconeogenesis.

The other examples where Biotin is required as a coenzyme are:

2) Acetyl-CoA carboxylase (ACC) catalyzes the binding of bicarbonate to acetyl-CoA to form malonyl-CoA (Figure-2). Malonyl-CoA is required for the synthesis of fatty acids.


Figure-2 -The carboxylation of Acetyl co A to form Malonyl co A, catalyzed by Acetyl co A carboxylase is the first and the rate limiting step in fatty acid synthesis.

3) Propionyl-CoA carboxylase catalyzes essential steps in the metabolism of certain amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules).

Fate of propionyl co A

Figure- 3-showing the fate of Propionyl co A

Propionyl co A is converted first to D- Methyl malonyl co A and then to its L isomer, ultimately to succinyl co A for complete utilization in the TCA cycle (Figure-3).

Anaplerotic reactions catalyzed by biotin dependent pyruvate carboxylase (PC) and Propionyl-coenzyme A carboxylase (PCC) regenerate oxaloacetate for the citric acid cycle.

As regards other options

B) Phospho enol pyruvate carboxykinase- Catalyzes the conversion of Oxaloacetate to phosphoenol pyruvate, it is an enzyme of pathway of gluconeogenesis but it is not a biotin dependent enzyme

C) Glucose-6-phosphatase catalyzes the last step of conversion of glucose-6-Phosphate to free glucose, but it is also not biotin dependent enzyme.

D) Fructose 1, 6 bisphosphatase- catalyzes the conversion of fructose1, 6 bisphosphate to Fructose 6 Phosphate; it is also not a biotin dependent enzyme.

E) Phosphoglycerate kinase- is a common enzyme, both for the pathways of glycolysis and gluconeogenesis. It catalyzes the reversible conversion of 1, 3 bisphosphoglycerate to 3, phosphoglycerate, ATP is formed by substrate level phosphorylation in glycolysis. ATP is consumed in the reverse reaction, in the pathway of gluconeogenesis.



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