ketone biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of ketones, a class of organic compounds that contain the carbonyl group, CO, and in which the carbonyl group is bonded only to carbon atoms. The general formula for a ketone is RCOR, where R and R are alkyl or aryl groups. [GOC:go_curators]

Ketone biosynthesis is a metabolic process that occurs primarily in the liver, generating ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) as an alternative energy source when glucose availability is limited. This process is triggered by prolonged fasting, starvation, or conditions like diabetes mellitus, where glucose uptake by peripheral tissues is impaired.

The process begins with the breakdown of fatty acids through β-oxidation in the liver mitochondria. Acetyl-CoA, a product of β-oxidation, is then utilized in the synthesis of ketone bodies.

**Step 1: Formation of acetoacetyl-CoA:** Two molecules of acetyl-CoA condense to form acetoacetyl-CoA, catalyzed by the enzyme thiolase.

**Step 2: Formation of HMG-CoA:** Acetoacetyl-CoA reacts with another molecule of acetyl-CoA, catalyzed by HMG-CoA synthase, to produce 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).

**Step 3: Formation of acetoacetate:** HMG-CoA is cleaved by HMG-CoA lyase, producing acetoacetate and acetyl-CoA.

**Step 4: Formation of β-hydroxybutyrate:** Acetoacetate can be reduced to β-hydroxybutyrate by β-hydroxybutyrate dehydrogenase, using NADH as a reducing agent.

**Step 5: Formation of acetone:** Acetoacetate can also spontaneously decarboxylate to form acetone, although this is a minor pathway.

Ketone bodies are released from the liver and transported to other tissues, such as the brain, heart, and skeletal muscles, where they can be used as fuel. β-hydroxybutyrate can be oxidized back to acetoacetate by β-hydroxybutyrate dehydrogenase, and acetoacetate is then converted to acetyl-CoA by the enzyme succinyl CoA:3-oxoacid CoA-transferase. Acetyl-CoA then enters the citric acid cycle to generate ATP.

The ketone biosynthetic process is tightly regulated by various hormones and factors, including insulin, glucagon, and the availability of glucose and fatty acids. During periods of fasting or low glucose availability, glucagon levels rise, stimulating fatty acid breakdown and ketone body production. Insulin, on the other hand, inhibits ketone biosynthesis by suppressing fatty acid release and promoting glucose uptake.'
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Proteins (1)

Compounds (9)