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Transcript
What is Ketosis? An excessive production of ketones in the blood 3 derivatives of acetyl-CoA Acetoacetate -hydroxybutyrate Acetone CH3CCH2COOO H CH3CCH2COOOH O CH3-C-CH3 What is the Significance of ketosis Acidosis Excessive acid in the blood Overflow Excessive oxidation of fatty acids Metabolic Problem Faulty Carbohydrate Metabolism Metabolic fate of Acetyl CoA Pyruvate minor Fatty Acids Acetyl-CoA major Citrate Ketone Bodies CH3C~SCoA O CH3C~SCoA O HS-CoA CH2C~SCoA CH3C + O rearrangement OH -Ketothiolase CH3CCH2C~SCoA O O Acetoacetyl-CoA CH3CCH2C~SCoA O O HS-CoA CH3C~SCoA O CH2C-OO CH3CCH2C~SCoA HO O OH OOC-CH2-C-CH2-C~SCoA CH3 O HMG-CoA Synthase -hydroxy--methyl glutaryl-CoA (HMG-CoA) OH OOC-CH2-C-CH2-C~SCoA HMG-CoA Acetoacetate CH3 O CH3-C~SCoA O OH + 2-C~SCoA HMG-CoA OOC-CH2-C-CH Lyase CH3 O OOC-CH2-C-CH3 O CO2 NADH + H+ NAD+ CH3-C-CH3 OOC-CH2-CH-CH3 O Acetone OH -hydroxybutyrate Diabetes Insufficient insulin production (Type I) Ineffective or impaired insulin function (Type II) Main Characteristics Failure to transport glucose into muscle and adipose tissue Failure to catabolize glucose at a normal rate in liver Excessive oxidation of fatty acids leading to ketosis Diabetes and Lipid Metabolism Whenever carbohydrates are not available for metabolism, fatty acid oxidation is accelerated A more rapid degradation of fatty acids augments production of acetoacetyl-CoA and acetyl CoA OAA is being used for gluconeogenesis Less carbohydrate means less pyruvate. Less pyruvate means less OAA. Less OAA means less citrate INSULIN Pancreas beta cells 5.8 kDa polypeptide Emulates the fed signal Lowers blood glucose Stimulates glycogen synthesis Stimulates glycolysis Stimulates lipid synthesis NO BACKUP Suppresses Glucagon GLUCAGON Pancreas alpha cells 3.5 kDa polypeptide Emulates the “need” signal Raises blood glucose Stimulates glycogen breakdown Stimulates gluconeogenesis GLUCORTICOIDS Stimulates lipolysis BACKUP ADIPOSE TISSUE Triacylglycerols Glucagon-stimulated lipase Glucose No glucose uptake by 3 fatty acids adipose Glycerol-PO4 DHAP 3 Fatty acids + Glycerol Glycerol kinase Missing in adipose tissue Blood Liver Breakdown of adipose lipids grossly accelerated FA Glucose Pyruvate LIVER Acetyl-CoA Acetyl-CoA Acetyl-CoA Acetyl-CoA Acetyl-CoA CO2 Ketone bodies OAA CITRATE Glucose All glucagon-stimulated activities take precedence