Page last updated: 2024-10-24

acetyl-CoA biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of acetyl-CoA, a derivative of coenzyme A in which the sulfhydryl group is acetylated. [GOC:go_curators]

Acetyl-CoA biosynthesis is a fundamental metabolic process that produces acetyl-CoA, a crucial two-carbon unit involved in various cellular functions, including energy production, lipid synthesis, and amino acid metabolism. The process occurs in the mitochondria of eukaryotic cells and involves several key steps:

1. **Pyruvate Dehydrogenase Complex (PDC) Activity:** The primary source of acetyl-CoA is the oxidation of pyruvate, a three-carbon molecule produced from the breakdown of carbohydrates (glycolysis). Pyruvate enters the mitochondria and is decarboxylated by the pyruvate dehydrogenase complex (PDC). This enzyme complex requires several cofactors, including thiamine pyrophosphate (TPP), lipoic acid, coenzyme A (CoA), flavin adenine dinucleotide (FAD), and nicotinamide adenine dinucleotide (NAD+). The PDC reaction generates carbon dioxide, NADH, and acetyl-CoA.

2. **Fatty Acid Oxidation:** Fatty acids, another major source of energy, are broken down into two-carbon units (acetyl-CoA) through a process called beta-oxidation. This process occurs in the mitochondria and involves a series of reactions that cleave the fatty acid chain two carbons at a time. Each round of beta-oxidation produces one molecule of acetyl-CoA, NADH, and FADH2.

3. **Amino Acid Catabolism:** Some amino acids, particularly those with carbon skeletons that can be converted to pyruvate, can be broken down into acetyl-CoA. This process involves a series of reactions that remove amino groups and convert the remaining carbon skeleton into acetyl-CoA.

4. **Other Sources:** Acetyl-CoA can also be generated from the degradation of ketone bodies and some specific amino acids.

5. **Regulation:** The biosynthesis of acetyl-CoA is tightly regulated to meet the cell's energy needs and to ensure the balance of metabolic pathways. The activity of the PDC is controlled by various factors, including the availability of substrates, the levels of ATP and NADH, and the presence of specific regulatory enzymes.

The acetyl-CoA produced in these pathways is essential for:

* **Citric Acid Cycle (Krebs Cycle):** Acetyl-CoA enters the citric acid cycle, a central metabolic pathway that generates ATP and reducing equivalents (NADH and FADH2) for oxidative phosphorylation.
* **Lipid Synthesis:** Acetyl-CoA is a key building block for the synthesis of fatty acids, cholesterol, and other lipids.
* **Amino Acid Synthesis:** Acetyl-CoA is involved in the synthesis of certain amino acids, such as leucine and lysine.
* **Other Cellular Processes:** Acetyl-CoA plays a role in the regulation of gene expression, detoxification reactions, and other cellular processes.'
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Proteins (2)

ProteinDefinitionTaxonomy
ATP-citrate synthaseAn ATP-citrate synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53396]Homo sapiens (human)
Malonyl-CoA decarboxylase, mitochondrialA malonyl-CoA decarboxylase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95822]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
hydroxycitric acidcarbonyl compound
methyl 5-(n-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)morpholine-4-carboxamido)pentanoatemethyl 5-(N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)morpholine-4-carboxamido)pentanoate: a malonyl-CoA decarboxylase inhibitor; structure in first source
3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamidebiphenyls