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by: Luke Holden


Marketplace > Clemson University > Biochemistry > 3050 > BCHM EXAM 4 WEEK 2 NOTES
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This set of notes contains the regulation of glycolysis, the Kreb's Cycle, and the regulation of the Krebs's. Hope this helps!
Essential Elements of Biochemistry
Dr. Srikripa Chandrasekaran
Class Notes
BCHM 3050
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This 7 page Class Notes was uploaded by Luke Holden on Tuesday April 12, 2016. The Class Notes belongs to 3050 at Clemson University taught by Dr. Srikripa Chandrasekaran in Winter 2016. Since its upload, it has received 36 views. For similar materials see Essential Elements of Biochemistry in Biochemistry at Clemson University.


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Date Created: 04/12/16
Exam 4 Week 2 Notes 4/4/16 Regulation of Glycolysis  Direct Modification of Enzymes o Pyruvate Kinase (Runners)  This is the only enzyme that is directly phosphorylated  Dephosphorylating will activate this enzyme   In this example, Insulin takes off the phosphate and glucagon puts it on  Glucokinase is a molecular sensor of high glucose levels  As blood sugar levels rise, so does the activity of the glucokinase. o This rise and fall of the activity is regulated by the Km of  the enzyme.  o The lower the Km the higher the affinity of the enzyme of  the substrate. o In addition, the regulation of glucokinase is regulated my  insulin as well.  Activators and Inhibitors o Steps that inhibit: 1,3,10 (all reactions with kinase) o Know them!  Availability of substrate  Allosteric Regulation Regulator Hexokinase (1) Phosphofructokinase Pyruvate Kinase (3) (10) Glucose 6P ­ Fructose­1,6P2 + AMP + + ADP + ATP ­ ­ Citrate ­ Acetyl CoA ­ Fructose 2,6­  + bisphosphate  o All this table has done is put the enzymes and their repective activators and  inhibitors in a table format Metabolic Fate of Pyruvate  Aerobic Respiration makes much more ATP (BUT YOU HAVE TO HAVE OXYGEN  FOR THE FINAL ELECTRON ACCEPTOR IN THE ETC)  Lactate is formed during exercise in the form of lactic acid. 4/6/16 Lactic Acid Fermentation  A common theme throughout the regulation process is the regeneration of NADH and  FADH2.   The cell knows that Lactic Acid fermentation is slow and inefficient. Thus, it does  everything it can to keep the ETC going since it substantially more effective.   Pyruvate (lactate dehydrogenase)Lactate  Glyceraldehyde 3­ Phosphate(Glyceraldehyde­P­ Dehydrogenase) Glycerate­1,3­  bisphosphate Alcoholic Fermentation  Note re Alcoholism: Ethanol stimulates synthesis of NADH in liver by ADH  The extra NADH will inhibit glycolysis and fatty acid oxidation  Acetylaldehyde Acetic Acid Fatty acid synthesis  Result is accumulation of fat in the liver o loss of function­ cirrhosis TO LEARN FROM GLYCOLYSIS and FERMENTAITON: 1. 13 enzymes  2. Substrates and Products  3. Where ATP is made and Invested 4. The order they go in Krebs cycle  Overview o The main purpose of this cycle is yes produce ATP but more importantly, produce Electron carriers such as NADH and FADH2 to power the electron pumps in the  ETC. o This cycle has a net return of:  6 NADH's are generated (3 per Acetyl CoA that enters)  2 FADH2 is generated (1 per Acetyl CoA that enters)  2 ATP are generated (1 per Acetyl CoA that enters)  4 CO2's are released (2 per Acetyl CoA that enters)  (Don’t forget that 2 NADH and 2 CO2 come from the transformation of  the pyruvate into 2 Acetyl Coa. o Pyruvate gets completely oxidized to CO2 o IN ORDER TO KEEP THE CYCLE GOING, OAXALOACETATE HAS TO BE REPRODUCED Things to remember when doing this cycle: 1. Name the enzyme 2. Count the Carbons 3. Know the substrates and products 4. Know the order they come in 5. Know where NADH, FADH, and ATP are produced I will talk about each enzyme as a step in the cycle (Starting with the oxidation of pyruvate to 2  acetyl coa even though this is not an official step)  Step 1 o Pyruvate(Pyruvate Dehydrogenase) 2 Acetyl Coa o This is the only reaction that occurs in both the mitochondrial matrix and the inner membrane  Step 2 o Oaxalacetate(from the previous cycle) + Acetyl Coa (Citrate Synthase) Citrate  Step 3 o Citrate(Aconitase) Isocitrate  Step 4 o Isocitrate +NAD(Isocitrate Dehydrogenase)Oaxalsuccinate +NADH+CO2  Step 5 o Oaxalsuccinate+ NAD ( α­Ketogluterate dehydrogenase) Succinyl Coa  +NADH +CO2  Step 6 o Succinyl Coa +GDP(Succinyl Coa synthase) Succinate o GTP phosphorylates ADP to ATP o WARNING, EVEN TOUGH THE ENZYME SAYS SYNTHASE, IT  REMOVES COA!!!!! DON’T BE TRICKED  Step 7 o Succinate +FAD(Succinate Dehydrogenase) fumerate +FADH2  Step 8 o Fumerate +H2O(Fumerase) Malate  Step 9 o Malate +NAD(Malate Dehydrogenase) Oaxalacetate +NADH REMEMBER FOR ALL OF THESE STEPS THAT THERE IS 2 COA GOING INTO THE  CYCLE SO YOU WILL MULTIPLY THE PRODUCTS BY 2 4/8/16 A closer look at the enzymes  pyruvate dehydrogenase o a complex of three separate enzymes o Promotes entry of pyruvate into the TCA via the formation of Acetyl Coa o Allosteric Regulation  Inhibitors:  ATP, acetyl Coa and NADH  Activators:  AMP, CoASH, and NAD o Covalent modification  Don’t have to know the first bullet point  PDH gets phosphorylated Regulator PFK1 Pyr. Kin Pyr.  Citrate  Isocit.  α­k­glt deHase synthase Dehydrogenas deHase e ATP ­ ­ ­ ­ ­ NADH ­ ­ ­ ­ ADP + + + + + AMP + + NAD+ + + + Citrate ­ Acetyl­ ­ ­ Coa Succinyl­  ­ ­ Coa  Succinate Dehydrogenase o SDH is a part of complex 2 of ETC o FADFADH2electrons go to the ETC o ATP is synthesized via Nucleoside diphosphate kinase o Regulation  Inhibition: OAA  Activation: Succinate and ATP+P  Malate Dehydrogenase o Anaplerotic­ reactions that form products of next reaction o SO ALL KREBS STEPS ARE ANAPLEROTIC o Malate is oxidized to OAA  and NADNADH o Forward reaction is not favored but the depeletion of OAA and the need for OAA  drives the reaction of OAA  Amphibolic nature of the TCA cycle o Acetyl­CoA fatty acids and sterols o Glutamate Proteins and Purines o Succinyl CoAporphyrins (hemes, and chlorophylls) o OAAgluconeogenesis (reversal of Krebs) o OAATCA cycle  Malate Dehydrogenase  Pyruvate Carboxylase  Both glycolysis & TCA cycle will stop unless oxidized  nucleotides are regenerated.


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