1. Ketone bodies<br />Synthesis & oxidation<br />Ketone bodies<br />Acetoacetate (Acetoacetic acid)<br />ßHBA-ß-hydroxybutyrate (3-hydroxybutyrate)<br />Acetone<br />These three substances are collectively known as the ketone bodies<br />Ketogenesis Occurs When There Is a High Rate of Fatty Acid Oxidation in the Liver.(when the amount of acetyl CoA exceeds the oxidative capacity)<br />[Total ketone bodies]in the blood of well-fed mammals does not normally exceed 0.2 mmol/L except in ruminants.<br />Extrahepatic tissues utilize them as respiratory substrates.( in starvation)<br />Skeletal muscles<br />Cardiac muscles<br />Renal cortex<br />Brain <br />Enzymes responsible for ketone body formation are associated mainly with the mitochondria. So not in RBC.<br />3-hydroxy-3-methylglutaryl-CoA synthase <br />3-Hydroxy-3-methylglutaryl-CoA lyase <br />Both enzymes must be present in mitochondria for ketogenesis to take place. <br />This occurs solely in liver and rumen epithelium. <br />ßHBA is quantitatively the predominant ketone body present in the blood and urine in ketosis.<br />Acetoacetate only oxidize among Ketone bodies<br />ßHBA<br />Acetone no use for the cell<br />No regulatory point in Ketogenesis pathway. Only regulation is Acetyl CoA.<br />Ketogenesis is regulated at 3 crucial steps: <br />(1) control of free fatty acid mobilization from adipose tissue.<br />Free fatty acids are the precursors of ketone bodies in the liver.<br />The factors regulating mobilization of free fatty acids from adipose tissue are important in controlling ketogenesis<br />(2) the activity of carnitine palmitoyltransferase-I (CPT-1)in liver, which determines the proportion of the fatty acid flux that is oxidized rather than esterified.<br />(3) partition of acetyl-CoA between the pathway of ketogenesis and the citric acid cycle. <br />Utilization of Ketone bodies<br />Liver produces Ketone bodies<br />Liver cannot use Acetoacetate as fuel.(lacks the enzyme for conversion of Acetoacetate> Acetoacetyl CoA)<br />Acetoacetyl CoA > 2 Acetyl CoA<br />Clinical Aspects<br />Higher than normal quantities of ketone bodies present in the blood (ketonemia (hyperketonemia) ) or urine (ketonuria)<br />The overall condition is called ketosis. <br />The basic form of ketosis occurs in starvation and involves depletion of available carbohydrate coupled with mobilization of free fatty acids.<br />During fasting or carbohydrate starvation, OAA is depleted in liver due to gluconeogenesis. This impedes entry of Acetyl CoA -> Krebs cycle <br />This general pattern of metabolism is exaggerated to produce the pathologic states found in diabetes mellitus & ….<br />Nonpathologic forms of ketosis are found under conditions of high-fat feeding and after severe exercise in the postabsorptive state.<br />Acetoacetic and ßHBA are both moderately strong acids and are buffered when present in blood or other tissues. However, their continual excretion in quantity progressively depletes the alkali reserve, causing ketoacidosis. This may be fatal in uncontrolled diabetes mellitus.<br />
![Ketone bodies<br />Synthesis & oxidation<br />Ketone bodies<br />Acetoacetate (Acetoacetic acid)<br />ßHBA-ß-hydroxybutyrate (3-hydroxybutyrate)<br />Acetone<br />These three substances are collectively known as the ketone bodies<br />Ketogenesis Occurs When There Is a High Rate of Fatty Acid Oxidation in the Liver.(when the amount of acetyl CoA exceeds the oxidative capacity)<br />[Total ketone bodies]in the blood of well-fed mammals does not normally exceed 0.2 mmol/L except in ruminants.<br />Extrahepatic tissues utilize them as respiratory substrates.( in starvation)<br />Skeletal muscles<br />Cardiac muscles<br />Renal cortex<br />Brain <br />Enzymes responsible for ketone body formation are associated mainly with the mitochondria. So not in RBC.<br />3-hydroxy-3-methylglutaryl-CoA synthase <br />3-Hydroxy-3-methylglutaryl-CoA lyase <br />Both enzymes must be present in mitochondria for ketogenesis to take place. <br />This occurs solely in liver and rumen epithelium. <br />ßHBA is quantitatively the predominant ketone body present in the blood and urine in ketosis.<br />Acetoacetate only oxidize among Ketone bodies<br />ßHBA<br />Acetone no use for the cell<br />No regulatory point in Ketogenesis pathway. Only regulation is Acetyl CoA.<br />Ketogenesis is regulated at 3 crucial steps: <br />(1) control of free fatty acid mobilization from adipose tissue.<br />Free fatty acids are the precursors of ketone bodies in the liver.<br />The factors regulating mobilization of free fatty acids from adipose tissue are important in controlling ketogenesis<br />(2) the activity of carnitine palmitoyltransferase-I (CPT-1)in liver, which determines the proportion of the fatty acid flux that is oxidized rather than esterified.<br />(3) partition of acetyl-CoA between the pathway of ketogenesis and the citric acid cycle. <br />Utilization of Ketone bodies<br />Liver produces Ketone bodies<br />Liver cannot use Acetoacetate as fuel.(lacks the enzyme for conversion of Acetoacetate> Acetoacetyl CoA)<br />Acetoacetyl CoA > 2 Acetyl CoA<br />Clinical Aspects<br />Higher than normal quantities of ketone bodies present in the blood (ketonemia (hyperketonemia) ) or urine (ketonuria)<br />The overall condition is called ketosis. <br />The basic form of ketosis occurs in starvation and involves depletion of available carbohydrate coupled with mobilization of free fatty acids.<br />During fasting or carbohydrate starvation, OAA is depleted in liver due to gluconeogenesis. This impedes entry of Acetyl CoA -> Krebs cycle <br />This general pattern of metabolism is exaggerated to produce the pathologic states found in diabetes mellitus & ….<br />Nonpathologic forms of ketosis are found under conditions of high-fat feeding and after severe exercise in the postabsorptive state.<br />Acetoacetic and ßHBA are both moderately strong acids and are buffered when present in blood or other tissues. However, their continual excretion in quantity progressively depletes the alkali reserve, causing ketoacidosis. This may be fatal in uncontrolled diabetes mellitus.<br />](https://image.slidesharecdn.com/ketonebodies-100324132715-phpapp02/85/Ketone-Bodies-Yapa-Wijeratne-1-320.jpg)
