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MoleculesMnemonicEnzymesMnemonicCoenzymesEnergeticsNomenclatureFunctionSite of SynthesisCompositionApoproteinsPrefix (# of carbons)Designation of Double Bond (Unsaturated)Unsaturated SuffixSaturated SuffixEnzymeAllostericCovalentInductionFatty AcidParent CompoundSourcesDrugCategoryActionReasonStudy Guide Exam 2TCA Cycle (Krebs Cycle; Citric Acid Cycle)TCA CYCLE:• Tricarboxylic Acid Cycle• Krebs Cycle• Citric Acid CycleOccurs in mitochondria, majority of reactions happen in liver cellsSome enzymes attached to inner membrane in mitochondrial matrix or cristae of membrane and some enzymes will be found free floating in the inner mitochondrial matrixIt is a common metabolic pathway for all the macronutrients:CHO oxidizing glucose  pyruvate  acetyl CoA (via pyruvate dehydrogenase complex enzyme)  krebs cycleLipids  triglycerides hydrolyzed to free fatty acids and those free fatty acids undergo beta-oxidation to give acetyl CoAProtein  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 cycleMain 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 coenzymesOne important regulation step : at equilibrium reaction would favor malate 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 GDPPyruvate  Malate OAA  PEP (decarboxy kinase) link between gluconeogenesis and TCA cyclePyruvate (from glycolysis)  Acetyl CoA (enters TCA cycle) via NAD  NADH + H+Energetics:• NADH = 3 ATP• FADH = 2 ATP• GTP = 1 ATPStarting TCA cycle from acetyl CoA molecule = 12 ATPGlucose = 2 Acetyl CoA = 24 ATP in TCA Cycle3 NADH * 3 = 9 ATP1 FADH * 2 = 2 ATP1 GTP * 1 = 1 ATP = 12 ATP TOTAL * 2 for each acetyl CoA = 24 ATP Starting TCA Cycle from pyruvate:Glycolysis = 2 Pyruvate = 2 Acetyl CoA = 30 ATP in TCA cycle4 NADH = 12 ATP1 FADH = 2 ATP1 GTP = 1 ATP = 15 ATP TOTAL * 2 for each acetyl CoA = 30 ATPLiver, 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 ATPIntermediates of TCA Cycle:Citrate  FAAlpha-ketoglutarate  Succinyl CoA OAA  Aspartate3 rate limiting enzymes:• Citrate synthetase• Isocitrate dehydrogenase• Alpha-ketoglutarate dehydrogenaseBeta-Oxidation:Diet/starvation mode: CHO Low, break down protein to have amino acids available for energy• Amino acid metabolism: glucogenic or ketogenic amino acidso Glucogenic amino acids: used to make glucose through gluconeogenesiso 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 glycolysisIn 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 decarboxylaseHard 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 ADPUncouple 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


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FSU HUN 3224 - Study Guide Exam 2

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