lecture 4 glycolysis Flashcards

1
Q

glucose has 3 paths

A

storage-> glycogen, starch
oxidation via glycolysis->pyruvate
oxidation via pentose phosphate pathway-> Ribose 5-phosphate

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2
Q

glycolysis

A

sweet splitting

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3
Q

glucose catabolism

A

carried out by all cells in cytoplasm

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4
Q

ten reactions

A

same in all cells

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5
Q

products of glycolysis

A

pyruvate,atp,NADH

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6
Q

3 fates for pyruvate

A

aerobic oxidation (CO2+H2O)
anaerobic oxidation into lactate
anaerobic fermentation into alcohol

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7
Q

3 catabolic fates of pyruvate

A

hypoxic or anaerobic conditions -> 2 ethanol +2CO2
aerobic conditions(CO2 LEAVES)-> Acetyl CoA-> citric acid cycle-> 4 CO2+ 4 H2O
anaerobic conditions -> 2 Lactate (in muscle, erythrocytes, some microorganisms)

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8
Q

one molecule of glucose 6C

A

degrades to 2 pyruvate molecules 3C

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9
Q

net energy yield of glycolysis

A

2 ATP and 2 NADH per glucose

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10
Q

glucose + 2NAD+ + 2ADP + 2 Pi

A

2 pyruvate + 2 NADH + 2 H++ 2 ATP + 2 H2O

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11
Q

glucose + 2 NAD+

A

2 pyruvate + 2 NADH + 2H+

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12
Q

2ADP + 2 Pi

A

2 ATP + 2 H2o

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13
Q

overall reaction

A

is irreversible and exergonic but more energy remains to be extracted

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14
Q
  1. prepatory phase
A

4 phases
converts 6 C sugar to 2 3C sugars
USES 2 ATP

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15
Q

payoff phase

A

6 steps
Converts 2 3C sugars to 2 pyruvates
MAKES 4 ATP (2 from each 3 C sugar)

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16
Q
  1. phsophorylation of glucose to glucose 6- phosphate
A

(Mg2+) metal cofactor of hexokinase shields - charges
large negative delta G
priming reaction- ATP is consumed
“traps glucose as glucose 6P which does not diffuse or bind to glucose transporters

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17
Q
A
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18
Q
  1. phosphorylation of Fructose- 6P to fructose 1,6 bisphosphate
A

(Mg2+)
phosphofructokinase-1
phosphoryl group transfer
first committed step, fructose 1,6 P is only targeted for glycolysis
second “priming reaction”

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19
Q

PFK1 activity is highly regulated by ATP levels in the cell

A

Activity is high when [ATP] is low
Activity is low when [ATP] is high
feedback inhibition

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20
Q
  1. cleavage of fructose 1,6 bisphosphate
A

NO Mg
aldolase
aldol condensation
generates isomers:
DHAP and GAP
point where pyruvate formation takes parallel paths

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21
Q
  1. Conversion of DHAP to GAP
A

only GAP can be directly degraded to pyruvate
triose phosphate isomerase
ketone to an aldehyde
completes preparatory phase of glycolysis

22
Q

the splitting of fructose 1,6 bisphosphate

A

DHAP is made from 1,2,3C
GAP is made from 4,5,6C
split by aldolase
DHAP to GAP done by triose phosphate isomerase

23
Q

summary of phase 1

A

4 steps
(5 counting DHAP-GAP)
converts one 6C to two 3C sugars
uses 2 ATP

24
Q

phase 2: the payoff
6. Oxidation of GAP to 1,3 bisphosphoglycerate

A

oxidation
payoff: NADH is made when NAD is reduced
1,3 BPG is high energy compound

NOT ATP -> inorganic phosphate

25
Q

phosphoryl transfer from 1,3 BPG to ADP

A

phosphoglycerate kinase
transfer from carboxyl P-group
1st ATP is made
“substrate-level phosphorylation”
enzyme named for reverse reaction
(gluconeogenesis)

26
Q

energy coupling of reactions

A

coupling processes through a common intermediate: a thioester bond formed between a cysteine in GAP DH enzyme & GAP
example: steps 6 and 7
glyceraldehyde 3P+ ADP + Pi + NAD+ (substrate, endergonic) -> 3P + ATP NADH +H+ (products, exergonic)
overall reaction is exergonic

27
Q

coupling processes through a common intermediate

A

a thioester bond formed between a cysteine in a GAP DH enzyme & GAP

28
Q

thioester intermediate

A

reduces the delta G of transition energy

29
Q

8 Conversion of 3-phosphoglycerate to 2-phosphoglycerate

A

Mg2+ cofactor
phosphoglycerate mutase
a mutase catalyzes the transfer of function group from one position to another on a molecule
(in this case phosphoryl from C3 to C2)
unique phosphorylated His

30
Q
  1. Dehydration of 2-phosphoglycerate to phosphoenolpyruvate
A

Enolase catalyzes the conversion of 2PG to a form from which more energy can be released
standard free energy for the hydrolysis of 2PG is only ~16 kJ / mol
-30 kJ/ mol necessary to drive ATP formation
dehydration of 2 PG to PEP by enolase creates a compound of driving synthesis of ATP

31
Q

10 phosphoryl transfer from PEP to ADP

A

final step
substrate level phosphorylation
2nd atp made
pyruvate is made
enzyme named for reverse reaction

32
Q

summary of phase 2

A

5 steps
converts GAP to pyruvate
makes 2 ATP (per GAP)
Makes 1 NADH (per GAP)

33
Q

overall glycolysis summary

A

overall net reaction of glycolysis is:
glucose +2NAD+ + 2 ADP +2 Pi -> 2 pyruvate + 2 NADH + 2ATP + 2 H2O +2 H+

34
Q

there is a net gain of 2 ATP per glucose molecule ( actually make 4 , but use 2 )

A

as glucose is oxidized, 2 NAD + are reduced to 2 NADH

35
Q

Aerobic - O2 is available

A
  • NADH is reoxidized in the electron transport pathway making ATP in oxidative phosphorylation
  • Pyruvate enters the citric acid cycle
36
Q

Anaerobic conditions

A

-NADH is re-oxidized to NAD+ providing additional NAD+ for more glycolysis
-pyruvate converted to lactate ( lactic acid fermentation: muscles)
-Pyruvate converted to ethanol( ethanol fermentation yeast)

37
Q

Fermentation

A

energy extraction ( i.e. ATP formation via substrate- level phosphorylation) without consumption of oxygen
no net change in concs of NAD+ or NADH

38
Q

fate of NADH & pyruvate

A

lactic acid fermentation ( ie muscle contraction)
Conversion of glucose to lactate:
includes two redox reactions, although no net change in oxidation state of carbons in glucose (C6H12O6) vs. lactate (C3H6O3)
no net change in oxidation; H:C ratios the same for glucose & lactate
even so, enough energy ( 2 ATP/ glucose) extracted in conversion of glucose to lactate

39
Q

fate of NADH & pyruvate

A

glucose makes 2 pyruvate and reduces 2 NAD to NADH
the 2 NADH oxidize when 2 pyruvate make 2 lactate
fermentation allows for regen of NAD+ in order to extract energy (ATP) from glucose under anaerobic conditions no net change in [NAD+] or [NADH]

40
Q

ethanol fermentation (ie yeast)

A

pyruvate loses CO2 from pyruvate decarboxylase to become acetaldehyde
acetaldehyde oxidizes NADH to NAD+ and makes ethanol with alcohol dehyrogenase

41
Q

Anaerobic fermentation vs oxidative phosphorylation

A

anaerobic fermentation results in the production of 2 ATP/ glucose

42
Q

oxidative phosphorylation

A

can yield up to 38 ATP/glucose

43
Q

pasteur effect

A

yeast consume more sugar when grown under anaerobic conditions

44
Q

hexokinase deficiency

A

Reduced glucose breakdown
Reduced ATP production
Reduced BPG production
Not as easy for Hb to
assume T-state

45
Q

PK deficiency

A

Reduced ATP production
RBCs become deformed/lyse
Hb carries less O2

46
Q

tumors

A

have enhanced glucose uptake and glycolysis rates

47
Q

glucose uptake correlates with tumor aggressiveness and poor prognosis

A
48
Q

cancer cells grow more rapidly than blood vessels that nourish them

A

-They become starved for oxygen (hypoxia)
-Need ATP

49
Q

hypoxic tumors produce HIF-1

A
  • hypoxia inducible transcription factor
50
Q

HIF-1 increases gene expression

A
  • glycolytic enzymes
    • GLUT 1 and 3
51
Q

HIF-1 stimulates the growth of vasculature

A
  • expression of signal molecules- vascular endothelial growth factor (VEGF)
    • another anti-cancer drug target