Ketone Bodies Metabolism PDF

Lippincott’s illustrated reviews Chapter 16 – Page 195 Lecture 28 Ketone Bodies Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Understand what is the ketone bodies and where can ketone bodies formed. Differentiat...

Lippincott’s illustrated reviews Chapter 16 – Page 195 Lecture 28 Ketone Bodies Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Understand what is the ketone bodies and where can ketone bodies formed. Differentiate between ketogenesis and ketolysis. Explain the relationship between ketone bodies and diabetic patient. 2 Ketone bodies The compounds categorized as ketone bodies are acetoacetate, 3-hydroxybutyrate, and acetone (a nonmetabolized side product). 3  Ketone bodies are important sources of energy for the peripheral tissues Because they are soluble in aqueous solution and, therefore, do not need to be incorporated into lipoproteins or carried by albumin as do the other lipids. This is particularly important during prolonged periods of fasting. 4  Ketone bodies are produced in the liver during periods when the amount of acetyl CoA present exceeds the oxidative capacity of the liver. 5  Ketone bodies are used in proportion to their concentration in the blood by extrahepatic tissues, such as the skeletal and cardiac muscle and renal cortex. Even the brain can use ketone bodies to help meet its energy needs if the blood levels rise sufficiently; thus, ketone bodies spare glucose. Important Note: Disorders of fatty acid oxidation present with the general picture of hypoketosis (due to decreased availability of acetyl CoA) and hypoglycemia (due to increased reliance on glucose for energy. 6  Synthesis of ketone bodies by the liver (Ketogenesis) During a fast, the liver is flooded with fatty acids mobilized from adipose tissue. This result in elevation in hepatic acetyl CoA produced primarily by fatty acid degradation. Part of this acetyl CoA enter krebs cycle which increase the level of its product which diminish the cycle. Therefore, acetyl CoA is channeled into ketone body synthesis. 7 8 Use of ketone bodies by the peripheral tissues: (Ketolysis) During fasting, ketone bodies are needed to provide energy to the peripheral tissue. Ketolysis occur in extrahepatic tissues, including the brain but excluding cells lacking mitochondria (for example, red blood cells). In contrast, although the liver actively produces ketone bodies, it lacks thiophorase and, therefore, is unable to use ketone bodies as fuel. 9 10 11  Excessive production of ketone bodies in diabetes mellitus When the rate of formation of ketone bodies is greater than the rate of their use, their levels begin to rise in the blood (ketonemia) and, eventually, in the urine (ketonuria). This is seen most often in cases of uncontrolled, type 1 diabetes mellitus. In diabetic individuals with severe ketosis, urinary excretion of the ketone bodies may be as high as 5,000 mg/24 hr, and the blood concentration may reach 90 mg/dl (versus less than 3 mg/dl in normal individuals). 12 13  A frequent symptom of diabetic ketoacidosis is a fruity odor on the breath, which results from increased production of acetone. An elevation of the ketone body concentration in the blood results in acidemia. Therefore, each ketone body loses a proton (H+) as it circulates in the blood, which lowers the pH of the body. 14 15  Excretion of glucose and ketone bodies in the urine results in dehydration of the body. Therefore, the increased number of H+, circulating in a decreased volume of plasma, can cause severe acidosis (ketoacidosis).] Ketoacidosis may also be seen in cases of fasting. 16 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 17