KETOGENESIS

1.Location of Ketogenesis:

🪶Ketogenesis occurs in the liver.

🪶The enzymes responsible for this process are located in the mitochondrial matrix.

2.Precursor for Ketone Bodies:

🪶Acetyl CoA, formed by the oxidation of fatty acids, pyruvate, or some amino acids, serves as the precursor for ketone bodies.

3.Formation of Acetoacetyl CoA:

🪶Two moles of acetyl CoA condense to form acetoacetyl CoA.

🪶This reaction is catalyzed by the enzyme thiolase.

4.Formation of HMG CoA:

🪶Acetoacetyl CoA combines with another molecule of acetyl CoA to produce 3-hydroxy-3-methylglutaryl-CoA (HMG CoA).

🪶HMG CoA synthase regulates this reaction.

5.Cleavage of HMG CoA:

🪶HMG CoA is cleaved by HMG CoA lyase to produce acetoacetate and acetyl CoA.

6.Fate of Acetoacetate:

🪶Acetoacetate can undergo spontaneous decarboxylation to form acetone.

🪶Alternatively, it can be reduced by a dehydrogenase to form β-hydroxybutyrate.

Utilization of Ketone Bodies

1.Transport of Ketone Bodies:

🪶Ketone bodies, being water-soluble, are easily transported from the liver to various tissues.

2.Energy Source:

🪶Acetoacetate and β-hydroxybutyrate serve as important sources of energy for peripheral tissues such as skeletal muscle, cardiac muscle, and renal cortex.

3.Tissues Lacking Mitochondria:

🪶Tissues lacking mitochondria (e.g., erythrocytes) cannot utilize ketone bodies.

4.Significance in Glucose Shortage:

🪶The production and utilization of ketone bodies become more significant when glucose is in short supply to the tissues, as observed in starvation and diabetes mellitus.

5.Prolonged Starvation:

🪶During prolonged starvation, ketone bodies are the major fuel source for the brain and other parts of the central nervous system (CNS).

6.Metabolism of β-Hydroxybutyrate:

🪶β-Hydroxybutyrate is first converted to acetoacetate and then metabolized. Acetoacetate is activated to acetoacetyl CoA by a mitochondrial enzyme, thiophorase.

7.Liver Utilization:

🪶Thiophorase is absent in the liver, hence ketone bodies are not utilized by the liver. Thiolase cleaves acetoacetyl CoA into two molecules of acetyl CoA.

Regulation of ketogeneses

1.ketone body formation:

🪶ketone bodies are permeable formed due to non availability of Carbohydrates to the tissues.

🪶This is an outcome excessive utilization of acids to meet the energy requirement of the cells.

2.Role of Hormones:

🪶The hormone glucagon stimulates ketogenesis, here as insulin inhibit it's .

3.Glucagon/Insulin Ratio:

🪶An increased ratio & glucagen to Insulin in diabetes mellitus promotes ketone body formation.

4.Disturbance Metabolism:

🪶That promotion of ketone body format ketone body formation in diabetes mellitus is due to disturbances caused by the metabolism, carbohydrates and lipid.

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