Molecular Classification
Enzyme, Biotin-dependent enzyme, Carboxylase
Other Names
Biotin carboxylase (BC), Acetyl-CoA carboxylase (ACC, a prototypical example), Propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC), Pyruvate carboxylase (PC), Urea carboxylase (UC)
Disease Roles
Metabolic disorders (deficiencies cause diseases such as propionic acidemia, 3-methylcrotonylglycinuria, pyruvate carboxylase deficiency)Cancer (drug target, particularly acetyl-CoA carboxylase)Type 2 diabetes and obesity (target for drug discovery)

Biotin-dependent carboxylase Overview

Biotin-dependent carboxylases are a conserved family of enzymes essential for a range of metabolic processes, including fatty acid, amino acid, and carbohydrate metabolism. They catalyze carboxylation reactions requiring biotin as a cofactor, functioning via a multistep mechanism that involves distinct enzymatic domains: a biotin carboxylase (BC) that activates and carboxylates biotin, a carboxyltransferase (CT) that transfers the carboxyl group to target substrates, and a biotin-carboxyl carrier protein (BCCP) that tethers and translocates biotin between domains. Multiple proteins in this family (such as acetyl-CoA carboxylase, propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and others) are implicated as therapeutic targets for cancer, diabetes, obesity, and infections, and as diagnostic markers for inborn metabolic diseases. The broad physiological roles and high degree of sequence conservation make this enzyme family both attractive and challenging as drug targets.

Mechanism of Action

Inhibition of enzymatic carboxylation activity, leading to interruption of downstream metabolic pathways essential for cell growth, fatty acid synthesis, or survival. Herbicidal action in plants by plastid ACC inhibition. Antibiotic mechanism via bacterial or fungal enzyme inhibition.

Biological Functions

Fatty acid metabolism
Amino acid metabolism
Carbohydrate metabolism
Polyketide biosynthesis
Urea utilization
Other general metabolic processes

Disease Associations

Metabolic disorders (deficiencies cause diseases such as propionic acidemia, 3-methylcrotonylglycinuria, pyruvate carboxylase deficiency)
Cancer (drug target, particularly acetyl-CoA carboxylase)
Type 2 diabetes and obesity (target for drug discovery)
Microbial infections
Other (herbicide target in plants)

Safety Considerations

  • Potential metabolic toxicity due to broad involvement in essential pathways (e.g., inhibition in humans could lead to hypoglycemia, neurological symptoms, or other metabolic abnormalities)
  • Specificity challenges: Inhibiting microbial/plant enzymes without affecting human homologs
  • Genetic mutations: Disease-causing mutations spread throughout structural and catalytic sites

Interacting Drugs

Experimental and investigational Acetyl-CoA carboxylase inhibitors (e.g., soraphen A, haloxyfop [in plants])
Some antibiotics and herbicides target biotin-dependent carboxylases in microbes or plants

Associated Biomarkers

Biomarker
Enzyme activity measurements (for metabolic screening of inborn errors)
Specific mutations (used in diagnosis of inborn errors of metabolism)