Kevin Ahern's BB 350 (Citric Acid Cycle) 2014 - #30

1. Contact me at [email protected] / Friend me on Facebook (kevin.g.ahern) 2. Download my free biochemistry book at http://biochem.science.oregonstate.ed... 3. Take my free iTunes U course at https://itunes.apple.com/us/course/bi... 4. Check out my free book for pre-meds at http://biochem.science.oregonstate.ed... 5. Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 6. Course video channel at http://www.youtube.com/user/oharow/vi... 7. Check out all of my free workshops at http://oregonstate.edu/dept/biochem/a... 8. Check out my Metabolic Melodies at http://www.davincipress.com/ 9. My courses can be taken for credit (wherever you live) via OSU's ecampus. For details, see http://ecampus.oregonstate.edu/soc/ec... 10. Course materials at http://oregonstate.edu/instruct/bb350 1. Regulation of glycogen phosphorylase is reciprocal to the regulation of glycogen synthase. Phosphorylation of the phosphorylase makes it more active and phosphorylation of the synthase inactivates it. Binding of epinephrine to a target cell activates phosphorylase at the same time as glycogen synthase is stopped. Removal of the phosphates is stimulated by insulin and reverses the effects. 2. Phosphorylation involves a signaling system that makes cAMP. The amount of cAMP never stays high for long because phosphodiesterase breaks it down fairly quickly. Caffeine is an inhibitor of phosphodiesterase. In this case, cAMP levels stay high longer, allowing more phosphorylation and higher levels of blood glucose. Highlights Citric Acid Cycle 1. The citric acid cycle occurs in mitochondria. The most important structures of mitochondria are the inner membrane, the matrix, and the cristae. 2. Oxidative decarboxylation of pyruvate (oxidative = NADH produced), occurs AFTER glycolysis in the mitochondrion, but BEFORE the Citric Acid Cycle. The reaction is catalyzed by the pyruvate dehydrogenase complex, to form acetyl-CoA. 3. The cyclic pathway of the citric acid cycle is considered to "start" with addition of acetyl-CoA to oxaloacetate (OAA) to form citrate. 4. Citrate is rearranged to isocitrate next. 4. The first oxidative decarboxylation in the citric acid cycle occurs in the third step, yielding NADH and a five carbon compound, alpha-ketoglutarate. 5. Oxidative decarboxylation of alpha-ketoglutarate occurs next. The product is a four carbon molecule, succinyl-CoA. The enzyme catalyzing this reaction uses the same coenzymes as pyruvate dehydrogenase. 6. The fifth step is where GTP is the triphosphate produced and coenzyme A is released. 7. Step 6 involves oxidation of succinate (by FAD, to produce FADH2), catalyzed by succinate dehydrogenase. It is the only enzyme of the cycle not found in the mitochondrial matrix. Instead, it is embedded in the inner mitochondrial membrane. Fumarate is the product of this reaction. 8. Addition of water to fumarate yields L-malate. The eighth step of the citric acid cycle involves oxidation of malate (by NAD+ to produce NADH) to yield oxaloacetate. This reaction is the simple oxidation of an alcohol to a ketone and is catalyzed by malate dehydrogenase. It is unusual in being a rare oxidation that requires input energy. This reaction is "pulled" by the next reaction. 9. Alphaketoglutarate and oxaloacetate can readily be converted into the amino acids glutamate and aspartate, respectively. Remember from previously that pyruvate can be converted to alanine, as well. 10. The citric acid cycle is called anaplerotic, which means "to fill up". Several of its intermediates are important in other anabolic and catabolic pathways. Alpha-ketoglutarate can be converted easily to glutamic acid (and vice-versa) and oxaloacetate can be converted to glucose or aspartic acid (and vice-versa). 11. The citric acid cycle is regulated largely at the level of availability of NAD+ and FAD. When these are low in abundance, the pathway slows or stops. 12. Citric acid cycle molecules play roles in catabolism AND anabolism. Many amino acids and fatty acids can be converted into molecules that get oxidized in the citric acid cycle. On the other hand, intermediates in the citric acid cycle can readily be converted to amino acids and/or fatty acids. 13. The glyoxylate cycle is a cycle found in plants, bacteria, and yeast, but not animals. It overlays the citric acid cycle, using many of its enzymes. Two enzymes are unique to the citric acid cycle. They include isocitrate lyase (breaks isocitrate into succinate and glyoxylate) and malate synthase (add acetyl-CoA to glyoxylate to make malate. 14. Because the glyoxylate bypasses the decarboxylations of the citric acid cycle, it produces two oxaloacetates with each turn of the cycle. This means one net extra oxaloacetate per turn of the cycle and it can be used to make glucose.