Lecture 19: Glycolysis

Question 1

Catabolism

Answer 1

-BREAKDOWN fuels into energy
-usually coupled with reducing equivalents of NADH

Question 2

How is energy generated in mammals

Answer 2

-oxidation of carbon compounds to CO2 and H2O using O2
-release ATP and NADH

-start with reduced carbon end with oxidized carbon

Question 3

Anabolism

Answer 3

-BIOSYNTHESIS from smaller molecules
-REQUIRES energy from ATP or NADPH

Question 4

NADH form

Answer 4

reduced

Question 5

NADPH vs NADH

Answer 5

-NADPH mostly used for ANABOLISM

Question 6

Regulation of metabolism

Answer 6

-feedback or feedforward control at:
-rate-limiting step
-commitment step

Question 7

rate-limiting step

Answer 7

slowest in pathway

Question 8

commitment step

Answer 8

first irreversible step unique to pathway

Question 9

irreversible steps usually involve

Answer 9

-high energy substrates
-ex: ATP

Question 10

Futile Cycles

Answer 10

-formed by irreversible reactions in opposite directions
-activation of both wastes energy

Question 11

Use of a futile cycle in the liver

Answer 11

-between glucose and glucose 1-phosphate as a buffer to maintain blood glucose levels

Question 12

To minimize energy loss of a futile cycle:

Answer 12

reactions only in one direction should be active at a given time
-gycolysis vs gluconeogenesis

Question 13

Types of regulation of metabolism

Answer 13

-transcriptional (slow)
-protein degradation (slow)
-allosteric regulation (fast)
-post-translational modification (fast)
-compartmentation (fast)

Question 14

Slow regulation of metabolism

Answer 14

-transcriptional/translational (induce genes)
-protein degradation (ubiquitin-proteasome or lysosomal proteolysis)

Question 15

Fast regulation of metabolism

Answer 15

-allosteric regulation (activators/inhibitors)
-post-translational modifications (phosphorylation)
-compartmentation (shuttling substrates to compartments for reactions)

Question 16

Compartmentation

Answer 16

-shuttling substrates to compartment for reactions
-fatty acid biosynthesis in cytosol
-oxidation in the mitochondria

Question 17

Difference in metabolism between organs

Answer 17

-utilize dif metabolic pathways
-organs must cooperate to optimize phsyiological responses

Question 18

Point of No return of Metabolism

Answer 18

-pyruvate (C3) to acetyl CoA (C2)

Question 19

Glycolysis overview

Answer 19

Glucose to fructose 1,6 to 2 glyceraldhyde 3-phosphate to 2 pyruvate
-cytosol
-harvest 2 ATP and 2 NADH

Question 20

1st reaction in glycolysis

Answer 20

Glucose + 2 ATP –> fructose 1,6 bisphosphate + 2 ADP

Question 21

2nd reaction in glycolysis

Answer 21

fructose 1,6 bisphosphate ((C6) –> 2 glycaeraldehyde 3-phosphate (C3)

Question 22

3rd reaction in glycolysis

Answer 22

2 G3P + 4 ADP + 2 NAD+ —> 2 pyruvate + 4 ATP + 2NADH

-net gain: 2 ATP and 2 NADH

Question 23

Priming reaction of glycolysis

Answer 23

1. Glucose + ATP = G6P +ADP (hexokinase)
2. G6P –> F6P (reversible)
3. F6P + ATP = F1,6B +ADP (6-phosphofructo1Kinase)

Question 24

Regulation of priming reactions

Answer 24

-insulin increases # of glucose transporters on cell membrane (EXCEPT LIVER)
-G6P inhibits G6P production (hexokinase)

Question 25

Regulation of hexokinase

Answer 25

-inhibited by G6P

Question 26

regulation of 6-phosphofructokinase

Answer 26

-activated by AMP, fructose2,6 -inhibited by ATP, citrate, H+

Question 27

Reactions coupled with ATP hydrolysis

Answer 27

-typically irreverdible

Question 28

G6p

Answer 28

-also used in glycogen synthesis and pentose phosphate pathway *inhibiting this would inhibit other process other than glycolysis

Question 29

Commitment step of glycolysis

Answer 29

-production of fructose1,6B *target this one instead to stop glycolysis

Question 30

AMP

Answer 30

-signal used by cells to sense energy status - AMP much much lower than ADP and then ATP in cells

Question 31

small decrease in ATP leads to

Answer 31

significant increase in AMP

Question 32

AMP-activated protein kinase (AMPK)

Answer 32

-critical role in cellular energy homeostasis

Question 33

Adenylate kinase reaction

Answer 33

2 ADP <-> ATP + AMP

Question 34

Keq

Answer 34

[ATP][AMP]/[ADP]^2 =1

Question 35

Regulation of glycolysis at Splitting steps

Answer 35

F1,6P all the way to phosphoenolpyruvate are unregulated -enzymes keep them at equilibrium -reversible

Question 36

Regulation of pyruvate kinase

Answer 36

-activated by F1,6B -inhibited by ATP and alanine -pyruvate is also used to make alanine

Question 37

Pyruvate

Answer 37

-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

Question 38

Glycogen

Answer 38

-excess glucose stored in liver and muscles -synthesis and breakdown regulated -used by liver to regulate blood glucose levels

Question 39

Glycogen synthesis

Answer 39

1. G6P --> G1P 2. G1P +UTP <--> Glycogen + UDP -inhibited again by G6P (inhibts hexokinase)

Question 40

Fructose

Answer 40

-does not increase blood insulin -different metabolism -same splitting enzyme (aldolase B) -+glucose=sucrose

Question 41

Fructose metabolism

Answer 41

1. fructose + ATP --> F1P + ADP (fructokinase) 2. F1P + ATP --> 2 G3P + ADP (aldolase B)

Question 42

Excess fructose

Answer 42

-accumulates F1P in liver cells -depletes ATP and phosphate which may cause liver damage

Question 43

Aldolase B

Answer 43

breaks 6 carbon to 3 carbon

Question 44

Which of the following CANNOT be a carbon source for gluconeogenesis? -pyruvate -lactate -alanine -acetyl CoA

Answer 44

acetyl CoA