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Bio Chemistry Chapter 16 Notes

by: Ashley Alaniz

Bio Chemistry Chapter 16 Notes BCH 361

Marketplace > Arizona State University > Biochemistry > BCH 361 > Bio Chemistry Chapter 16 Notes
Ashley Alaniz
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These notes cover the main points of Chapter 16
Principles of Biochemistry
Alexander Green
Test Prep (MCAT, SAT...)
Bio Chemistry BCH 361
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This 4 page Test Prep (MCAT, SAT...) was uploaded by Ashley Alaniz on Thursday March 31, 2016. The Test Prep (MCAT, SAT...) belongs to BCH 361 at Arizona State University taught by Alexander Green in Fall 2015. Since its upload, it has received 11 views. For similar materials see Principles of Biochemistry in Biochemistry at Arizona State University.


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Date Created: 03/31/16
BIO CHEMISTRY (BCH 361) Prof. Green Chapter 16: Glycolysis  Glycolysis: energy­ conversion pathway that breaks down to produce ATP, pyruvate, and NADH  glucose is the most prominent monosaccharide fuel: ◦ potential for prebiotic synthesis ◦ the most stable hexose  ◦ low tendency to glycosylate proteins   occurs in two stages: ◦ Stage 1: Preparatory phase ◦ Stage 2: Payoff phase (ATP production) Hexokinase →  transfers phosphoryl group from ATP to a variety of hexoses  this reaction is irreversible in most organisms  Phosphorylation of glucose serves two purposes: 1. keeps glucose 6­phosphate from leaving cell (no longer a substrate for transporters) 2. addition of phosphate group is essential to downstream glycolytic reactions  Phosphoglucose Isomerase → converts an aldose into a ketose   glucose 6­phosphate and fructose 6­phosphate are isomers of one another Phosphofructkinase (PFK) → acts on the phosphofructose to add the second phosphate group   irreversible under cellular conditions   key regulatory enzyme for glycolysis Adolase   reversible reaction Triose Phosphate Isomerase  triose phosphate isomerase (TPI or TIM) catalyzes the reversible conversion between DHAP  and GAP  96% of triose phosphate is in the DHAP form, at equilibrium   consumption of GAP in glycolysis drives production of more GAP GAPDH: Making High Energy Phosphate  glyceraldehyde 3­phosphate dehydrogenase (GAPDH) converts GAP into 1,3­ biphosphoglycerate (1,3­BPG)  produces NADH employed in other reactions  ◦ occurs in two stages: 1. exergonic stage: oxidation of aldehyde to make carboxylic acid 2. endergonic stage: joining of carboxylate acid and orthophosphate Recouping ATP Input  phosphoglycerate kinase transfers high energy phosphate of 1,3­BPG to ADP to form ATP  formation of ATP in this manner is called subtrate­level phosphorylation  Generating ATP Output  Phosphoglycerate mutase shifts the position of the phosphoryl group  Enolase carries out a condensation reaction to produce the unstable phosphoenolpyruvate (PEP) ◦ PEP as the highest phosphate transfer potential of any molecule found in living cells   Pyruvate kinase then irreversibly transfers the phosphoryl group to ATP and forms pyruvate  since two PEP molecules are produced for each glucose, this step produces a gain of two ATP's Regulation of Glycolysis  Glycolysis accomplishes two main functions: 1. ATP generation 2. Building block for biosynthetic reactions  Glycolysis is regulated at irreversible reactions by three allostericenzymes: 1. Phosphofructokinase (PFK) 2. Hexokinase 3. Pyruvate kinase  Regulation varies depending on whether the reaction is being carried out in skeletal muscle or  the liver Regulation in Muscle  muscles require ATP to power the contraction  glycolysis is stimulated when the energy charge falls   Phosphofructokinase: the most important control site ◦ PFK has an ATP binding site away from the catalytic site ◦ ATP binding lowers affinity for fructose 6­phosphate ◦ AMP competes for binding site with ATP, but does not inhibit fructose 6­phosphate binding ◦ PFK is more inhibited as ATP/AMP ratio increases ◦ low PFK is more inhibited a ATP/AMP ration increases ◦ low pH (e.g. from lactic acid fermentation) also inhibits PFK     Hexokinase: ◦ inhibited by its own product glucose 6­phosphate  ◦ glucose 6­phosphate also builds up to inhibit hexokinase    Pyruvate kinase: ◦ inhibited by ATP  ◦ activated by fructose 1,6­bisphosphate so that it can respond to high PFK turnover ▪ this is an example of feedforward stimulation  Regulation in the Liver  liver has multiple functions: ◦ maintaining blood­glucose levels through glycogen storage and glucose release ◦ uses glucose to generate reducing power for biosynthesis ◦ building blocks for biosynthesis   the liver regulates glycolysis in a more complicated way than skeletal muscle PFK in the Liver  PFK can still be inhibited by ATP and pH in the liver, but these compounds are more stable in  the liver   PFK in the liver is inhibited by citrate, an early intermediate in the citric acid cycle  Fructose 2,6­bisphosphate: signaling molecule used to regulate blood­glucose level Glucokinase in the Liver  glucokinase replaces most of the hexokinase  glucokinase is an isozyme or isoenzyme for hexokinase  Isozymes: enzymes encoded by different genes with different amino acid sequences, yet  catalyze the same reactions Pyruvate Kinase in the Liver  pyruvate kinase has two isozymes: L for the liver and M for muscle (and brain)  the L form has additional regulatory behavior compared to the M form   high concentrations of alanine inhibit the L form  ◦ pyruvate is used to synthesize alanine   the L form can be inactivated via phosphorylation, which is used to respond to blood­glucose  levels  Glucose Transporters   glycolysis is also regulated by transport of glucose into the cell    *** in the body , [glucose] = 4mM to 8 mM *** Glucose Transporters and Cancer  cancer cells reproduce rapidly and thus are very metabolically active  many tumors will show enhanced rates of glucose uptake and glycolysis  tumors convert pyruvate → lactate  ◦ this lowers the pH and possibly prevents immune system detection  using a glucose analogue radioactive tracer, it is possible to visualize glucose uptake at tumors  (T) in a PET scan  knowing the molecular mechanisms of cancer, we can devise smarter therapeutics    Glycoconjugates: Trojan horse strategy ◦ conjugate a drug to glucose to deliver chemotherapy directly to cancer cells     Antisense Oligonucleotides: Translation Blocking ◦ use a sequence antisense to GLUT1 mRNA to stop it from being translated 


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