Carboxylic acids are deeply involved in metabolism because their –COOH group makes them chemically reactive, water-soluble, and ideal for energy transformations and biosynthesis. Here are the main ways they appear in metabolic pathways:
1. Key metabolic intermediates
Many central metabolites are carboxylic acids:
- Pyruvic acid (pyruvate) – end product of glycolysis; connects to the citric acid cycle, gluconeogenesis, and amino acid metabolism.
- Lactic acid (lactate) – formed during anaerobic metabolism from pyruvate.
- Citric acid, succinic acid, fumaric acid, malic acid, oxaloacetic acid – all intermediates of the citric acid (Krebs/TCA) cycle.
- These acids function as energy carriers and precursors for biosynthesis.
2. Energy metabolism
- Acetyl-CoA contains an activated carboxylic acid derivative (a thioester). It’s the entry point for the citric acid cycle, where carboxylic acids are oxidized to CO₂, releasing ATP.
- Oxidation and decarboxylation of carboxylic acids (like pyruvate → acetyl-CoA + CO₂) release energy and drive metabolism.
3. Fatty acid metabolism
- Fatty acids are long-chain carboxylic acids. Their β-oxidation involves sequential removal of two-carbon units as acetyl-CoA, feeding into the citric acid cycle.
- Fatty acid synthesis also starts from carboxylic acid derivatives (malonyl-CoA, acetyl-CoA).
4. Amino acid metabolism
- Many amino acids are carboxylic acids with an amino group (α-amino acids).
- Their metabolism often involves transamination, decarboxylation, or conversion into TCA intermediates (e.g., glutamate ↔ α-ketoglutarate).
5. Regulation and signaling
- Some small carboxylic acids act as signaling molecules (e.g., butyrate, propionate—short-chain fatty acids produced in the gut that regulate gene expression and immune responses).
- They can influence enzyme activity via allosteric regulation (e.g., citrate regulating glycolysis).