HNF 461 Lecture 16 Outline of Last Lecture I Type I Diabetes II Clinical Glucose Units III Diagnosis of Diabetes IV Prediabetes V Management of Diabetes VI Type II Diabetes a Progression b Management Treatment VII Hypoglycemia a Preprandial b Postprandial VIII Alcohol a Metabolism b Microsomal Ethanol Oxidizing System c Consequences Outline of Current Lecture I Postabsorptive Fuel Sources II Lipolysis III Fatty Acid Oxidation in the Muscle IV Beta Oxidation V Hepatic Fatty Acid Oxidation VI Ketogenesis VII Ketones as a Source of Energy VIII Ketosis IX Ketoacidosis These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute Current Lecture Lipolysis Fatty Acid Oxidation and Ketogenesis 1 Postabsorptive Fuel Sources a Postabsorptive State The state of the body a few hours after a meal metabolism is no longer relying on the nutrients from the most recent meal b Low blood glucose triggers metabolism of various fuels c Increased glucagon and epinephrine secretion decreased insulin secretion d Leads to hepatic glycogenolysis by increasing epinephrine levels e Leads to lipolysis 2 Lipolysis a Hormone Sensitive Lipase HSL located in adipose cells i Hydrolyzes triglycerides to yield non esterfied fatty acids NEFA ii Activated by glucagon binding to receptor increased cAMP increased PKA phosphorylation of HSL lipolysis b NEFA carried by albumin through blood to tissues for oxidation 3 Fatty Acid Oxidation in the Muscle a Muscle uses NEFA for energy in postabsorptive state b NEFA is activated to fatty acid CoA FACoA in cytoplasm c Carnitine is used to transport FACoA to mitochondria i Carnitine carnitine fatty acid FACoA CoA catalyzed by CAT1 ii Carnitine fatty acid carnitine CoA FACoA catalyzed by CAT2 iii Shuttle is inhibited by malonyl CoA at CAT1 4 Beta Oxidation a Within mitochondria b 2 carbons released from fatty acid yields 1 acetyl CoA 1 FADH2 and 1NADH c Acetyl CoA enters TCA cycle to yield CO2 NADH FADH2 and GTP d If oxygen is present NADH and FADH2 are transferred to ETC to produce ATP 5 Hepatic Fatty Acid Oxidation a Same process as in the muscle b Extra acetyl CoA is produced in the liver i Acetyl CoA TCA cycle ii Extra acetyl CoA is used to produce ketones 6 Ketogenesis a Occurs in the liver b 2 Acetyl CoA 1 Acetoacetyl CoA Acetoacetate c Acetoacetate B hydroxybutyrate consumes NADH NAD which goes back to FA oxidation d Acetoacetate Acetone tiny amount e Acetoacetate B hydroxybutyrate and acetone are all ketones f Occurs when blood NEFA concentration is low in starvation state and in diabetes fat cells are unresponsive to insulin glycolysis will not occur and a higher amount of fatty acids are in blood liver absorption of FA increases 7 Ketones as a Source of Energy a Ketones are not used by the liver b Water soluble transported to the muscle and brain for oxidation to spare glucose during starvation state c Oxidized in mitochondria to acetyl CoA and then transferred to TCA cycle and ETC 8 Ketosis a Excess production of ketones caused by high plasma NEFA b Ketones in urine increase urine output and loss of electrolytes c Ketones are acid and cause blood to become more acidic lowers pH 9 Ketoacidosis a Buffers to control blood pH i Exhale more CO2 to elevate pH of blood ii Buffer in kidney production of ammonia by deamination of amino acids b If lung and or kidney functions impaired can get acidosis c Symptoms loss of appetite vomiting smell of acetone on breath frequent urination dehydration d Treatment several large doses of glucose to stop excess NEFA release i For diabetics fluid replacement electrolyte replacement and insulin
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