Amino acids can be converted into fatty acids through a metabolic process that involves breaking down the amino acid and utilizing its carbon skeleton in fatty acid synthesis.
Amino Acid Degradation and Acetyl-CoA Production
The conversion of amino acids to fatty acids is an indirect process. It starts with the breakdown (degradation) of amino acids. This process yields two main products:
- Ammonium (NH4+): This is processed through the urea cycle for excretion.
- Carbon Skeleton: This is the remaining part of the amino acid and it's this carbon skeleton that's eventually used to create fatty acids.
The carbon skeletons are converted into various metabolic intermediates, including:
- Pyruvate
- Acetyl-CoA
- Other Krebs cycle intermediates (e.g., oxaloacetate, α-ketoglutarate, succinyl-CoA, fumarate)
Of these, acetyl-CoA is the key intermediate in fatty acid synthesis.
Fatty Acid Synthesis from Acetyl-CoA
Acetyl-CoA, generated from the carbon skeletons of amino acids, is then used in the process of fatty acid synthesis. This process primarily occurs in the cytoplasm.
- Acetyl-CoA Transport: Because fatty acid synthesis occurs in the cytosol and acetyl-CoA is formed in the mitochondria, acetyl-CoA must be transported across the mitochondrial membrane. This happens via the citrate shuttle. Acetyl-CoA combines with oxaloacetate to form citrate, which can cross the membrane. In the cytosol, citrate is broken down back into acetyl-CoA and oxaloacetate.
- Acetyl-CoA Carboxylation: Acetyl-CoA is carboxylated to form malonyl-CoA. This is a critical, committed step in fatty acid synthesis and is catalyzed by the enzyme acetyl-CoA carboxylase (ACC).
- Fatty Acid Synthase (FAS): Malonyl-CoA and acetyl-CoA are then used by fatty acid synthase, a large multi-enzyme complex. FAS catalyzes a series of reactions that sequentially add two-carbon units (from malonyl-CoA) to the growing fatty acid chain.
- Chain Elongation: The process continues, adding two-carbon units with each cycle, until a saturated fatty acid, such as palmitate (16 carbons), is formed.
- Further Modification: Palmitate can then be further elongated or desaturated (double bonds introduced) in the endoplasmic reticulum.
Summary of the Conversion
In essence, the amino acid conversion to fatty acids is a two-step process: degradation of amino acids into acetyl-CoA (or precursors that feed into acetyl-CoA production) and subsequent synthesis of fatty acids from acetyl-CoA. The first step frees the carbon backbone of the amino acid. The second builds fatty acids from that carbon by way of acetyl-CoA and other helper molecules.
