The significance of Ketone Body formation: Overall accumulation in urine and blood =ketosis Elevated ketone body formation: 50 – 100x higher >20 mg/100mL = ketonemia >70 mg/100 mLflushes out of kidneys and excreted into the urine = ketonuria The sweet smell of acetone is on the breath Two ketone bodies are acids. From citric acid cycle Acetyl CoA can now enter citric acid cycle Acetoacetate: Water soluble transportable acetyl CoA The pathway using acetoacetate as a fuel. Acetoacetate converts into the other two ketone bodies 2 acetyl CoA + H2O acetoacetate + 2 CoA + H+ Ketogenesis involves the production of ketone bodies from acetyl CoA. condensing 2 acetyl-CoA acetoacetyl-CoA HMG-CoA Synthase Condensation forms hydroxymethylglutaryl-CoA HMG-CoA Lyase splits HMG-CoA acetoacetate + acetyl-CoA. Two 4 carbon chain acids & a 3 carbonketone Early stages of starvation, when last remnants of fat are oxidized, heart & skeletal muscles will consume ketonebodies preserving glucose for the brain. Acetyl CoA cannot be processed in Krebs cycle! ģ Ketone Bodies: Inadequate amount of oxaloacetate in turn increases release of ketone bodies from liver for use as fuel by other tissues. ![]() Oxaloacetate already present is used in.Inadequate amount of oxaloacetate forms.Long-term fasting: starvation, crash diets, Loozen’s blackberry eradication program, etc.Diabetes: body cannot process glucose properly.What upsets the lipid / carbohydrate balance? Conversion to oxaloacetate uses pyruvate carboxylase enzyme. Oxaloacetate forms from pyruvate The product of glycolysis. Acetyl CoA from FA spiral processed in Krebs cycle. Ketone Bodies Usually lipid and carb metabolism are balanced. Liver prefers to use fatty acids Brain only uses glucose & ketone bodies 1 gram of carbohydrates = 4 kcal (food calories) 1 gram of fat = 9 kcal of energy Which fuel is the most commonly used? Skeletal muscles at rest use fatty acids Active skeletal muscles use glucose Cardiac muscles: 1st fatty acids, then Ketone bodies, glucose, & lactate. In terms of energy from food: Fatty acids yield > 2x the energy per gram. activation) =120 ATP!Īn 18C stearic fatty acid will create = 120 ATP 1 Glucose will = 32 ATP 1 Stearic acid will = 120 ATP 3x 6C Glucose = 18 Carbons 32 ATP x 3 =96 ATP Lipids are 25% more efficient at energy storage! and oxidative phosphorylation.ĪTP production from Fatty Acid Oxidation An 18C stearic fatty acid will create: 9 acetyl CoA, which form 90 ATP 8 FADH2 which form 12 ATP & 8 NADH which form 20 ATP Total = 122 ATP (-2 ATP for F.A. These are processed in Krebs cycle, E.T.C. spiral make: one NADH & one FADH2 One Acetyl CoA forms at each turn, & two Acetyl CoA form at last step. List the details of Glycerol Metabolism ĪTP production from Fatty Acid Oxidation How does energy output compare to glucose oxidation? All turns (except last) of the F.A.Describe Triglyceride Storage & Mobilization.Outline the Digestion and Absorption of Lipids. ![]() Severe disorders can be fatal! Companies selling nutritional products promote carnitine as an important dietary supplement. People with lowcarnitine levels often have lipid deposition in the muscles, become irritable & weak. Long chain fatty acids are transported across the inner mitochondrial membrane in the form of acyl carnitine. Reminder: an acyl group is derived from a carboxylic acid (like a fatty acid) with its –OH group removed Uses a carrier protein: carnitine (derivative of amino acid lysine) Found in red meats & dairy products, can also be synthesized by the body. The longer chain F.A.s cannot diffuse across mitochondrial membrane - must be transported. ![]() Summary of fatty acid activation: fatty acid + ATP acyl-adenylate + PPi PPi 2 Pi acyladenylate + HS-CoA acyl-CoA + AMP Overall: fatty acid + ATP + HS-CoAacyl-CoA + AMP + 2 Pi Thiokinase Reactions of the fatty acid spiral for an 18:0 fatty acid (stearic acid).Repeats as a spiral because each section becomes shorter by 2 carbons ![]() Fatty acid repeatedly oxidized, cycling thru 4 reactions: produces Acetyl CoA, FADH2, & NADH.Fatty acid must be transported into mitochondrial matrix: uses a shuttle mechanism.Fatty acid must be activated: bond to coenzyme A.Fatty acid oxidation 3 steps to break down fatty acids to make energy
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