Lecture 19: Glycolysis Flashcards
Catabolism
-BREAKDOWN fuels into energy
-usually coupled with reducing equivalents of NADH
How is energy generated in mammals
-oxidation of carbon compounds to CO2 and H2O using O2
-release ATP and NADH
-start with reduced carbon end with oxidized carbon
Anabolism
-BIOSYNTHESIS from smaller molecules
-REQUIRES energy from ATP or NADPH
NADH form
reduced
NADPH vs NADH
-NADPH mostly used for ANABOLISM
Regulation of metabolism
-feedback or feedforward control at:
-rate-limiting step
-commitment step
rate-limiting step
slowest in pathway
commitment step
first irreversible step unique to pathway
irreversible steps usually involve
-high energy substrates
-ex: ATP
Futile Cycles
-formed by irreversible reactions in opposite directions
-activation of both wastes energy
Use of a futile cycle in the liver
-between glucose and glucose 1-phosphate as a buffer to maintain blood glucose levels
To minimize energy loss of a futile cycle:
reactions only in one direction should be active at a given time
-gycolysis vs gluconeogenesis
Types of regulation of metabolism
-transcriptional (slow)
-protein degradation (slow)
-allosteric regulation (fast)
-post-translational modification (fast)
-compartmentation (fast)
Slow regulation of metabolism
-transcriptional/translational (induce genes)
-protein degradation (ubiquitin-proteasome or lysosomal proteolysis)
Fast regulation of metabolism
-allosteric regulation (activators/inhibitors)
-post-translational modifications (phosphorylation)
-compartmentation (shuttling substrates to compartments for reactions)
Compartmentation
-shuttling substrates to compartment for reactions
-fatty acid biosynthesis in cytosol
-oxidation in the mitochondria
Difference in metabolism between organs
-utilize dif metabolic pathways
-organs must cooperate to optimize phsyiological responses
Point of No return of Metabolism
-pyruvate (C3) to acetyl CoA (C2)
Glycolysis overview
Glucose to fructose 1,6 to 2 glyceraldhyde 3-phosphate to 2 pyruvate
-cytosol
-harvest 2 ATP and 2 NADH
1st reaction in glycolysis
Glucose + 2 ATP –> fructose 1,6 bisphosphate + 2 ADP
2nd reaction in glycolysis
fructose 1,6 bisphosphate ((C6) –> 2 glycaeraldehyde 3-phosphate (C3)
3rd reaction in glycolysis
2 G3P + 4 ADP + 2 NAD+ —> 2 pyruvate + 4 ATP + 2NADH
-net gain: 2 ATP and 2 NADH
Priming reaction of glycolysis
- Glucose + ATP = G6P +ADP (hexokinase)
- G6P –> F6P (reversible)
- F6P + ATP = F1,6B +ADP (6-phosphofructo1Kinase)
Regulation of priming reactions
-insulin increases # of glucose transporters on cell membrane (EXCEPT LIVER)
-G6P inhibits G6P production (hexokinase)
Regulation of hexokinase
-inhibited by G6P
regulation of 6-phosphofructokinase
-activated by AMP, fructose2,6
-inhibited by ATP, citrate, H+
Reactions coupled with ATP hydrolysis
-typically irreverdible
G6p
-also used in glycogen synthesis and pentose phosphate pathway
*inhibiting this would inhibit other process other than glycolysis
Commitment step of glycolysis
-production of fructose1,6B
*target this one instead to stop glycolysis
AMP
-signal used by cells to sense energy status
- AMP much much lower than ADP and then ATP in cells
small decrease in ATP leads to
significant increase in AMP
AMP-activated protein kinase (AMPK)
-critical role in cellular energy homeostasis
Adenylate kinase reaction
2 ADP <-> ATP + AMP
Keq
[ATP][AMP]/[ADP]^2
=1
Regulation of glycolysis at Splitting steps
F1,6P all the way to phosphoenolpyruvate are unregulated
-enzymes keep them at equilibrium
-reversible
Regulation of pyruvate kinase
-activated by F1,6B
-inhibited by ATP and alanine
-pyruvate is also used to make alanine
Pyruvate
-product of glycolysis
-transported to mitochondria to be turned into acteyl CoA (oxidative decarboxylation)
-can be used to make glucose through gluconeogenesis
-can also make alanine and lactate
Glycogen
-excess glucose stored in liver and muscles
-synthesis and breakdown regulated
-used by liver to regulate blood glucose levels
Glycogen synthesis
- G6P –> G1P
- G1P +UTP <–> Glycogen + UDP
-inhibited again by G6P (inhibts hexokinase)
Fructose
-does not increase blood insulin
-different metabolism
-same splitting enzyme (aldolase B)
-+glucose=sucrose
Fructose metabolism
- fructose + ATP –> F1P + ADP
(fructokinase) - F1P + ATP –> 2 G3P + ADP
(aldolase B)
Excess fructose
-accumulates F1P in liver cells
-depletes ATP and phosphate which may cause liver damage
Aldolase B
breaks 6 carbon to 3 carbon
Which of the following CANNOT be a carbon source for gluconeogenesis?
-pyruvate
-lactate
-alanine
-acetyl CoA
acetyl CoA
