From the Guidelines
Pyruvate carboxylase is the key biotin-dependent enzyme that becomes active during fasting and contributes significantly to gluconeogenesis. This enzyme catalyzes the conversion of pyruvate to oxaloacetate, which is the first committed step in the gluconeogenesis pathway [ 1 ]. During fasting, when blood glucose levels drop, pyruvate carboxylase activity increases to help maintain blood glucose homeostasis by promoting the synthesis of new glucose from non-carbohydrate precursors. The enzyme requires biotin as an essential cofactor to function properly, as biotin serves as a carrier for carbon dioxide in the carboxylation reaction.
Some key points about pyruvate carboxylase include:
- It is primarily located in the mitochondria of liver and kidney cells, where most gluconeogenesis occurs [ 1 ]
- Its activity is upregulated during fasting by increased levels of acetyl-CoA (which accumulates during fatty acid oxidation) and by hormones like glucagon and cortisol, which are elevated during fasting states
- Biotin deficiency can impair pyruvate carboxylase activity and consequently reduce gluconeogenesis capacity, potentially leading to hypoglycemia during fasting periods [ 1 ]
The biotin cycle, as described in [ 1 ], highlights the importance of biotin in various metabolic processes, including gluconeogenesis, fatty acid synthesis, and amino acid catabolism. The cycle involves the conversion of dietary biotin into active holocarboxylases, which are then degraded to produce free biotin that can be recycled. This process ensures a continuous supply of biotin for various biotin-dependent enzymes, including pyruvate carboxylase.
In the context of fasting, the activation of pyruvate carboxylase is crucial for maintaining blood glucose levels, and any impairment in its activity due to biotin deficiency can have significant consequences for glucose homeostasis [ 1 ]. Therefore, it is essential to ensure adequate biotin intake, especially during periods of fasting or when glucose homeostasis is critical.
From the Research
Biotin-Dependent Enzymes and Fasting
- Pyruvate carboxylase (PC) is a biotin-dependent enzyme that plays a crucial role in gluconeogenesis, lipogenesis, and amino acid catabolism 2, 3, 4.
- During fasting, pyruvate carboxylase is active and contributes to gluconeogenesis, which is the process of generating glucose from non-carbohydrate sources 5.
Role of Pyruvate Carboxylase in Gluconeogenesis
- Pyruvate carboxylase catalyzes the carboxylation of pyruvate to form oxaloacetate, which is a critical step in gluconeogenesis 3, 4.
- The enzyme is allosterically regulated by acetyl-CoA and aspartate, and its activity is essential for maintaining blood glucose levels during fasting and other physiological states 5, 3.