BCHM 3050 1st Edition Lecture 32Outline of Last Lecture I. Step 8II. Step 9III. Step 10IV. Pyruvate KinaseV. Glucokinase vs. HexokinaseVI. Energy InvestmentVII. Energy PayofVIII. Regulation of GlycolysisIX. Metabolic Fate of PyruvateX. Lactic Acid FermentationXI. Alcohol Fermentation XII. Practice QuestionsOutline of Current Lecture I. The Citric Acid CycleII. Summary of ReactionIII. Mitochondria UltrastructureIV. Overview of the Citric Acid CycleV. Enzymes of the Citric Acid CycleVI. Pyruvate DehydrogenaseVII. Citrate SynthaseVIII. Succinate DehydrogenaseCurrent LectureI. The Citric Acid Cyclea. Krebs was Knighted as “Sir” Hans Krebs by Queen Elizabeth II in 1958 (like Paul McCartney). This is a British symbolic title of honor.b. Also called “tricarboxylic cycle” (tricarboxylic molecule is used) and “citric acid cycle” (citric acid is the compound that is regenerated)II. Summary of Reactiona. Pyruvate is a 3 carbon atom containing moleculeb. 2 molecules of pyruvate at startc. 4 NADH, 1 FADH2, 3 CO2, GTP are the products of this reactiond. Enzyme converts pyruvate into acetyl-coA which carries out the Krebs cycleà pyruvate itself doesn’t actually carry out the krebs cycleThese 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.e. Pyruvate dehydrogenase is the enzyme that catalyzes the step before the start of the Krebs cyclef. Inside of the mitochondria is the matrix, where pyruvate dehydrogenase is found àpyruvate processing àpyruvate loses 2 CO2à forming acetyl-coA (2 molecules of NADH formed)g. Start with 6 carbon glucose in glycolysis à all carbon atoms are broken down and released at 6 CO2 moleculesIII. Mitochondria Ultrastructurea. Localization of PDH complex thought to be loosely associated with inner membrane/matrix interface.b. Thought to originally have been a prokaryotec. Mitochondria has its own DNAd. Krebs cycle and pyruvate processing occur in the matrixe. Cristae (folds) is the same thing as the “inner membrane”f. PDH (pyruvate dehydrogenase complex) is found on the inner member/matrixIV. Overview of the Citric Acid Cyclea. Know how many carbon atoms are present in each state, when CO2, NADH, FADH, ATP, ADP are all releasedb. Pyruvate is going to become completely oxidized into CO2c. Substrate level phosphorylation à 1 ATP after each round of Krebs (so 2 ATPs once both pyruvates have gone through the cycle)d. 3 carboxylic acid groups in citric acidV. Enzymes of the Citric Acid Cyclea. Pyruvate dehydrogenaseb. Citrate synthasec. Aconitased. Isocitrate dehydrogenasee. a-Ketoglutarate dehydrogenasef. Succinyl-CoA synthetaseg. Succinate dehydrogenaseh. Fumarasei. Malate dehydrogenasej. Enzymes labeled in yellow show where NADH or FADH2 are createdk. Step 1: Occurs in mitochondria matrix, loses CO2, generates NADH, oxidation reduction reaction (pyruvate dehydrogenase belongs to the category of oxioreducatase enzymes)l. CoA – 2 carbon atomsm. Isocitrate – 6 carbon atomsn. Whenever you make an NADH, enzyme is a dehydrogenaseo. Succinyl-CoA synthetase converts succinyl-coA to succinate (only one that does substrate level phosphorylation to create ATP in this cycle)p. Succinate àfumarate, generates FADH2 (oxioreducatase)q. Break down bond of fumerate using water to created malate (break in the presence of water is hydrolase)r. Malate àoxaloacatate, generate NADH, oxioreductaseVI. Pyruvate Dehydrogenasea. Thiamine pyrophosphate is derived from Thiamine (vitamin B1).b. Know the names of the enzymes, co-factors, functions, but not # of copiesc. Someone with vitamin B deficiency does not make TPP, cannot carry out respiration very welld. Note: The activators & inhibitors of PDH are not acting via their inhibitory & activating efects on PDH Kinase. Each enzyme has their own binding sites for the same regulators.e. Glucose-6-phosphate can inhibit hexokinase (product inhibits enzyme in step 1 for glycolysis) f. Acetyl-coA product inhibits enzymes just like step 1 of glycolysisg. Pyruvate dehydrogenase can be inactivated by phosphorylationi. last enzyme in glycolysis (pyruvate kinase) is inhibited by phosphorylationVII. Citrate Synthasea. Acetyl Carbonion: acetyl group where one of the CH3 protons falls away leaving :CH2-CO-SCoA radical.b. - Enzyme is inhibits by its substrate – ATP inhibits phosphofructokinase 1 yet ATP also serves as its substratec. Succinyl-coA is a downstream inhibitord. Acetyl coA and OAA stimulateVIII. Succinate Dehydrogenasea. Succinate dehydrogenase sits in the inner membrane and is part of the complex in the electron transport chainb. ATP activates in this step rather than inhibiting (like all of the other
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