TCA Cycle Krebs Cycle Citric Acid Cycle Study Guide Exam 2 TCA CYCLE Tricarboxylic Acid Cycle Krebs Cycle Citric Acid Cycle Occurs in mitochondria majority of reactions happen in liver cells Some enzymes attached to inner membrane in mitochondrial matrix or cristae of membrane and some enzymes will be found free floating in the inner mitochondrial matrix It is a common metabolic pathway for all the macronutrients CHO oxidizing glucose pyruvate acetyl CoA via pyruvate dehydrogenase complex enzyme krebs cycle Lipids triglycerides hydrolyzed to free fatty acids and those free fatty acids undergo beta oxidation to give acetyl CoA Protein glucogenic synthesize glucose through gluconeogenesis and ketogenic form ketone bodies amino acids acetyl CoA Some amino acids can be transaminated to pyruvate glutamate or ketoglutarate intermediates except for pyruvate but once it is converted to pyruvate it can be converted to acetyl CoA and then enters the TCA cycle Main purpose of TCA Cycle Reduce coenzymes which will later be re oxidized in the ETC and oxidation will be coupled with phosphorylation to from ATP regenerate OAA in order to continue reducing coenzymes One important regulation step however because OAA is continuously being removed to form citrate you end up forming more OAA instead of having malate being formed Since OAA is combined with acetyl CoA to form citrate ten that favors the reaction by having more OAA synthesized rather than malate in order to keep cycle going Succinyl CoA high energy compound converted to Succinate is a step in TCA cycle but also a link to how gluconeogenesis is related to the TCA cycle GTP is formed from GDP Pyruvate Malate OAA PEP decarboxy kinase link between gluconeogenesis and TCA cycle Pyruvate from glycolysis Acetyl CoA enters TCA cycle via NAD NADH H at equilibrium reaction would favor malate Energetics NADH 3 ATP FADH 2 ATP GTP 1 ATP 15 ATP TOTAL 2 for each acetyl CoA 30 12 ATP TOTAL 2 for each acetyl CoA 24 ATP Starting TCA cycle from acetyl CoA molecule 12 ATP Glucose 2 Acetyl CoA 24 ATP in TCA Cycle 3 NADH 3 9 ATP 1 FADH 2 2 ATP 1 GTP 1 1 ATP Starting TCA Cycle from pyruvate Glycolysis 2 Pyruvate 2 Acetyl CoA 30 ATP in TCA cycle 4 NADH 12 ATP 1 FADH 2 ATP 1 GTP 1 ATP ATP Liver kidneys and cardiac muscle end up with 38 ATP because of the malate dehydrogenase shuttle the 2 NADH that was formed in glycolysis was transported to the membrane through the shuttle since NADH is not permeable to the membranes malate will transport the H s and the coenzyme NAD inside the membrane will receive the H NADH AEROBIC CONDITIONS If happening in skeletal muscle or brain 36 ATP would be formed because the glyceraldehyde dehydrogenase shuttle enzyme in mitochondria receives H and coenzyme is FAD forming FADH FADH less ATP synthesis Glycolysis Glucose 2 Pyruvate 8 ATP 2 ATP 2 NADH Oxidation of Pyruvate Acetyl CoA 6 ATP 1 NADH x 2 cause it happens twice TCA Cycle Acetyl CoA 12 ATP x 2 24 ATP Intermediates of TCA Cycle Citrate FA Alpha ketoglutarate Succinyl CoA OAA Aspartate 3 rate limiting enzymes Citrate synthetase Isocitrate dehydrogenase Alpha ketoglutarate dehydrogenase Beta Oxidation Diet starvation mode CHO Low break down protein to have amino acids available for energy Amino acid metabolism glucogenic or ketogenic amino acids o Glucogenic amino acids used to make glucose through gluconeogenesis o Ketogenic amino acids used to form ketone bodies and oxidized for energy which is Acetyl CoA Acetyl CoA is accumulating because there is a decrease in OAA which is how ketone bodies are formed A decrease in OAA will inhibit citrate synthase the cycle is not happening at the speed it should be happening Acetyl CoA is a positive modifier for pyruvate carboxylase allosteric Pyruvate is then converted to OAA by entering Krebs cycle Increase in Acetyl CoA inhibits PDH because PDH will convert pyruvate to Acetyl CoA which you don t want anymore How to get pyruvate from our energy deprived cells scarce CHO in our bodies and the brain can function with ketone bodies but glucose is main Main substrate for the brain is glucose if you are fasting or low CHO diet glucagon and epinephrine will increase which means glycolysis will decrease and you will not be able to get pyruvate via glycolysis In order to form pyruvate transamination of amino acids will occur Alanine alpha ketoglutarate is transaminated pyruvate and glutamate via ALT OR SGPT alanine transaminase or serum glutamic pyruvic transaminase then pyruvate OAA via pyruvate decarboxylase Hard to stay at the same rate because glycolysis is still happening and Acetyl CoA is going to be accumulating once acetyl CoA is accumulated you inhibit citrate synthetase and acetyl CoA will be deviated to form ketone bodies which are then decarboxylated to form acetyl CoA Fatty Acid Oxidation Regulations End product inhibitions a lot of NADH will inhibit dehydrogenases ATP will inhibit citrate synthase and isocitrate dehydrogenase citrate will also inhibit citrate synthase succinyl CoA inhibits alpha ketoglutarate dehydrogenase and citrate synthase alpha ketoglutarate dehydrogenase catalyzes the rxn to succinyl CoA from alpha ketoglutarate Electron Transport Chain ETC Main purpose capture energy in the form of ATP and coupling 2 processes oxidation and phosphorylation occurs in mitochondria Oxidation oxidizing coenzymes that were reduced in previous pathways loss of hydrogens or pair of electrons Phosphorylation in order to produce ATP you need to phosphorylate ADP Uncouple these pathways uncontrolled energy produced 40 energy produced is coupled for the formation of ATP 60 energy will be uncoupled released as heat to maintain body temp adipose tissue Proton Pumps in ETC Also called respiratory chain because the oxidation of this coenzyme is linked to the uptake of oxygen aerobic requires oxygen 4 complexes embedded in the inner membrane 1 Complex I NADH Q oxidoreductase a Removing protons from coenzyme and pumps protons into the inner mitochondrial membrane b NADH dehydrogenase 2 Complex II Succinate Q reductase a Does not pump protons into the inner mitochondrial membrane b FADH and Succinic dehydrogenase 3 Complex III Q cytochrome C oxidoreductase a Removing protons from coenzyme and pumps protons into the inner mitochondrial membrane b Cytochrome C 4 Complex IV Cytochrome C oxidase 2 mobile complexes Not Reversible Substances that can diffuse to the membrane 1 Ubiquinone coenzyme Q a Removing protons from coenzyme and pumps
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