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Ketogenesis pathway. The three ketone bodies (acetoacetate, acetone, and beta-hydroxy-butyrate) are marked within orange boxes. Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids.
Ketone bodies are water-soluble molecules or compounds that contain the ketone groups produced from fatty acids by the liver (ketogenesis). [1] [2] Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA (acetyl-Coenzyme A) – which then enters the citric acid cycle (Krebs cycle) and is oxidized for energy.
n/a n/a Ensembl n/a n/a UniProt n a n/a RefSeq (mRNA) n/a n/a RefSeq (protein) n/a n/a Location (UCSC) n/a n/a PubMed search n/a n/a Wikidata View/Edit Human Hydroxymethylglutaryl-CoA lyase HMG-CoA lyase dimer, Human Identifiers EC no. 4.1.3.4 CAS no. 9030-83-5 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB ...
The ketones are released by the liver into the blood. All cells with mitochondria can take up ketones from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver.
Acetoacetate decarboxylase (AAD or ADC) is an enzyme (EC 4.1.1.4) involved in both the ketone body production pathway in humans and other mammals, and solventogenesis in bacteria. Acetoacetate decarboxylase plays a key role in solvent production by catalyzing the decarboxylation of acetoacetate, yielding acetone and carbon dioxide. [1]
In humans, D-β-hydroxybutyrate can be synthesized in the liver via the metabolism of fatty acids (e.g., butyrate), β-hydroxy β-methylbutyrate, and ketogenic amino acids through a series of reactions that metabolize these compounds into acetoacetate, which is the first ketone body that is produced in the fasting state.
In physiological ketosis, ketones in the blood are elevated above baseline levels, but the body's acid–base homeostasis is maintained. This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency.
It is the most common exogenous ketone body because of its efficient energy conversion and ease of synthesis. [1] In the body, BHB can be converted to acetoacetic acid. It is this acetoacetic acid that will enter the energy pathway using beta-ketothialase, becoming two Acetyl-CoA molecules. [1]