Lecture 27 Glycolysis.docx

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Michael Baker

BCH210H © Lisa | Page 12 Lecture 27: Glycolysis  during muscle contraction, ATP is converted to ADP  NRG is used  chemical NRG converted to mechanical NRG  ATP level falls as NRG is used in contraction  need to replenish the ATP  phosphocreatine are phosphate donors that supply ATP  PCr are in higher levels in muscle  PCr supports ATP by giving its P to ADP to make ATP  this rxn is favourable bc PCr has a higher ΔG of hydrolysis than γ-P in ATP  when PCr is diminished, need glucose from blood  glucose enters muscle cell by GLUT4 (transporter)  GLUT4 allows glucose to flow down its conc gradient  glucose is used to produce NRG  glucose is used to support glycolysis (breaking of sugar in the muscle cytoplasm)  aerobic glycolysis breaks glucose into 2 3-C pyruvate molecules  pyruvate is joined by ATP production from glycolysis and NADH is generated  pyruvate then goes into mitochondria through pyruvate transporters  inner membrane of mitochondria has the transport fxs  outer membrane has pores  pyruvate participates mitochondrial oxidation rxns  pyruvate dehydrogenase (PDH) complex (a multienzyme complex) takes CO away from p2ruvate, leaving an acetyl group (2-C) and NADH  NADH is used later to make ATP  acetyl coA enters Krebs cycle  2CO r2leased, 3 NADH, 1 FADH produ2ed  electrons of NADH and FADH are 2sed in electron transport to give ATP through oxidative phosphorylation  NADH and FADH gene2ate a lot of ATP  glycolysis is an NRG conversion pathway  occurs in cytoplasm of most cells in the body  glycolysis has 10 enzymes associated w it  to break down glucose into the 3-C pyruvates  2 major stages  ATP-investment—enzymes 1-5  need to invest ATP before getting a lot back  energize glucose w ATP  ATP-production—6-10 Hexokinase  hexokinase is not specific to glucose (broad specificity)  α-D-glucose, mannose, fructose  ATP is transferring P to glucose (favourable rxn)  rxn is irreversible BCH210H © Lisa| Page 212  glucose enters by going down conc gradient  when glucose in blood decreases, glucose would be lost  this process tags the glucose by adding P  glucose-6-P is highly charged  keeps glucose in the cell for use  when liver makes glucose from glycogen, the flow is reversed  glu goes from inside liver cell to blood  glu can flow in both dir depending on conc  glu-6-P can feedback on HK to slow it down  inhibition by product  this process can be slowed it glu-6-P builds up  this is the control stage for glycolysis  Mg is needed as a counter ion for production of ATP in cells  it is the flavour of ATP that cells like  glu-6-P is then transformed into fructose-6-P  isomerase rxn PFK-1  addition of P from ATP to C-1 to produce β-D-fru-1,6-bisP and ADP  the molecule now has 2P  favourable rxn, irreversible to product side  also imp control point  PFK-1 can be inhibited by high levels of ATP (enzyme only requires low level of ATP to work)  glycolysis is to make ATP, thus a lot of ATP inhibits pathway  AMP overcomes the ATP inhibition  removes ATP inhibition  ATP and AMP are allosteric modulators, inhibits, and activates respectively  AMP allows PFK-1 to come to full strength  if one step in a pathway is slow, it will be the limiting factor  PFK-1 is a slow step, thus AMP gives it stimulation (AMP is the lowest end product [ATP to ADP, then AMP])  AMP is a sensitive regulator for PFK-1  in the liver, PFK-1 is also regula
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