Metabolism of Ketone Bodies 123456789123456789

Metabolism of Ketone Bodies

1. Metabolism of Ketone Bodies

2. Ketogenesis (ketone bodies formation) The fate of Acetyl CoA is either the entry into the Kreb cycle or the ketogenetic pathway Ketogenesis leads to the production of ‘ketone bodies’ in the form of acetone, hydroxybutyrate and acetoacetate In diabetes and starvation when  -oxidation of fatty acids increase leading to increased acetyl CoA. Because of increased gluconeogenesis, there is depletion of kreb cycle intermediates leading to shunting of Acetyl CoA into ketogenesis which primarily occurs in mitochondria of the liver

3. Ketone Bodies Acetoacetate , β- hydroxybutyrate and acetone are collectively known as ketone bodies . These are water soluble energy yielding substances. Acetone is, however, an exception , since it cannot be metabolized and is readily exhaled through lungs .

4. Ketogenesis Ketogenesis means the formation of ketone bodies . Liver is the only organ that synthesizes ketone bodies. The synthesis of ketone bodies occurs in mitochondrial matrix of hepatic cells. Ketone bodies are synthesized in the liver from acetyl-CoA formed by the β -oxidation of fatty acids .

5. Synthesis of ketone bodies

6. Utilization of Ketone Bodies The site of production of ketone bodies is the liver . But the liver cannot utilize ketone bodies because it lacks the particular enzyme CoA-transferase which is required for the activation of ketone bodies. Acetoacetate, β- hydroxybutyrate and acetone diffuse from the liver mitochondria into the blood and are transported to peripheral tissues.

7. Ketone bodies are catabolized to acetyl-CoA , which in turn enters the TCA cycle for the production of energy.

8. Significance of Ketogenesis Ketogenesis is a mechanism that allows the liver to oxidize increasing quantities of fatty acids. During deprivation of carbohydrate as in starvation and diabetes mellitus, acetoacetate and β- hydroxybutyrate serve as an alternative source of energy for extrahepatic tissues such as skeletal muscle, heart muscle, renal cortex, etc. In prolonged starvation 75 % of the energy needs of the brain are supplied by ketone bodies reducing its need for glucose.

9. Disorders of Ketone Body Metabolism

10. Ketosis Ketosis is referred to the overall condition of ( ketonemia and ketonuria ) and it means increased production or levels of ketone bodies. Ketonemia : is a condition of increased ketone bodies concentration in the blood . Ketonuria : is a condition of increased ketone bodies concentration in the urine . Ketonemia eventually leads to excretion of ketone bodies into the urine resulting in ketonuria .

11. Ketoacidosis The acidosis caused by over production of the ketone bodies acetoacetate and β- hydroxybutyrate (moderately strong acids) which causes a decrease in the pH of the blood . Acetoacetate and β- hydroxybutyrate acids when present in high concentration in blood, are buffered by HCO 3 – ( akali ) fraction of bicarbonate buffer . The excessive use of HCO 3 – depletes the alkali reserve causing ketoacidosis .

12. Ketone bodies concentration is much higher in ketoacidosis than in ketosis and in the absence of ketoacidosis risk factors, ketosis is generally considered safe. Ketoacidosis is seen in type I diabetes mellitus. ketoacidosis is relatively rare in type II diabetes.

13. Compound lipid Metabolism

14. Compound lipids include phospholipids, glycolipids, and lipoproteins. 1. Phospholipids: Phospholipids are important structural components of cell membranes. They are synthesized in the endoplasmic reticulum and Golgi apparatus. Phospholipid metabolism involves turnover processes, where old or damaged phospholipids are replaced by newly synthesized ones. 2. Glycolipids: Glycolipids are also constituents of cell membranes, particularly in nerve cells. Their metabolism involves synthesis in the endoplasmic reticulum and Golgi apparatus, similar to phospholipids. 3. Lipoproteins: Lipoproteins transport lipids (including triglycerides, cholesterol, and phospholipids) through the bloodstream. Metabolism of lipoproteins involves synthesis in the liver and intestine, where they are assembled and released into circulation. Lipoprotein metabolism is tightly regulated and plays a crucial role in lipid homeostasis and cardiovascular health . Compound Lipid Metabolism

15. 1 . Dietary Cholesterol: Cholesterol is obtained from dietary sources, primarily animal products. It is absorbed in the small intestine and packaged into chylomicrons for transport to the liver. 2. Endogenous Synthesis: The liver is the primary site of cholesterol synthesis. Synthesis begins with acetyl-CoA and proceeds through a series of enzymatic reactions, primarily mediated by the enzyme (3-hydroxy-3-methylglutaryl-coenzyme A ) HMG-CoA reductase. Cholesterol synthesis is tightly regulated by feedback mechanisms, including transcriptional control of HMG-CoA reductase and post-translational regulation by cholesterol levels. 3. Utilization and Transport: Cholesterol is an essential component of cell membranes and is also a precursor for steroid hormones, bile acids, and vitamin D. It is transported in the bloodstream within lipoprotein particles, primarily low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers cholesterol to tissues, while HDL helps remove excess cholesterol from peripheral tissues and transports it back to the liver in a process called reverse cholesterol transport. 4. Excretion: Cholesterol can be excreted from the body via bile secretion into the intestine. In the intestine, cholesterol can either be reabsorbed or excreted in feces, depending on the balance of cholesterol absorption and synthesis. Cholesterol Metabolism: