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pg 547 converts pyruvate to lactate, toring the pool of NAD +
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Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Dec 14, 2015

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Athena Castell
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Page 1: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

pg 547

LDH converts pyruvate to lactate, restoring the pool of NAD+

Page 2: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

pg 547

What about when pyruvate leaves the cytoplasm…?

?

Page 3: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +
Page 4: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Glycerol 3-P shuttle

fig19-30

Page 5: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle

fig19-29

Page 6: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle

Page 7: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle viewed as e- carrying process

OAA OAA

malate malate

NADH

NAD+

NADH

NAD+

Page 8: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle viewed as e- carrying processwith set of transaminations between OAA/Asp, and aKG/Glu

malate malate

NADH

NAD+

NADH

NAD+

OAA OAA

AspAsp

aKGaKG

Glu Glu

Page 9: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle viewed as e- carrying process

malate malate

NADH

NAD+

NADH

NAD+

OAA OAA

Page 10: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

with set of transaminations between OAA/Asp, and aKG/Glu

OAA OAA

AspAsp

aKGaKG

Glu Glu

Page 11: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

with set of transaminations between OAA/Asp, and aKG/Glu

OAA OAA

AspAsp

aKGaKG

Glu Glu

Page 12: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

with set of transaminations between OAA/Asp, and aKG/Glu

OAA OAA

AspAsp

aKGaKG

Glu Glu

NH3 groupfrom Asp to

aKG

NH3 groupfrom Glu to

OAA

Page 13: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle viewed as e- carrying processwith set of transaminations between OAA/Asp, and aKG/Glu

malate malate

NADH

NAD+

NADH

NAD+

OAA OAA

AspAsp

aKGaKG

Glu Glu

Page 14: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Malate-aspartate shuttle

fig19-29

Page 15: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +
Page 16: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

coupling is…

chemiosmotic

Page 17: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

e- flow is coupled to ATP production

Page 18: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

ACCEPTORCONTROL

fig19-33 bottom

Why doeslimited ADPdecrease therate of resp.chain?

or…

Page 19: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

low ADP NADH

fig19-33 middle

NADH and ATP/ADP levels directlyaffect the Krebs cycle…

Page 20: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

ADP ATP

fig19-33 middle

NADH and ATP/ADP levels directlyaffect the Krebs cycle…

Page 21: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig19-33 top

and glycolysis is similarlyaffected by ATPcitrate andNADH

Page 22: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig19-33the whole darn thing…

regulation of all three phasesof glucose break-down: acombination ofeffects of a number of molecules, including NADH,ATP, citrate,acetyl-CoA

Page 23: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig19-34

Nature’selectricblanket

use of uncouplingfor a biological purpose

Page 24: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

The “new” field of mitochondrial medicine

mitochondrial roles in

apoptosis (programmed cell death)

diabetes

ageing

Parkinsonism

Page 25: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

part II intro fig4

Anabolism!!!

Page 26: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-15

Carbohydratesynthesis inthe biosphere

Page 27: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Gluconeogenesis

anabolic production of glucose

Page 28: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-16

Carbohydratesa two-lane highway…

what determinesthese specialsteps?

Page 29: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

The glycolysis energy landscape

(pyruvate set to 0)

Page 30: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Three big steps down… or up

table 14-2

Page 31: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-17

First bypass

Page 32: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-17

First bypass

Page 33: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-17

First bypass, second step

Page 34: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-19

Two ways tomake PEP…

Page 35: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-20

two fates for pyruvate

Page 36: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

table 14-4

Page 37: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-16 top

Three big steps on theway up…

Page 38: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-15

Remember regulation ofPFK-1??

Page 39: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Fructose bisphosphate is at a key position in both cat and ana

Page 40: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig15-16

When glucose is abundant, so is F2,6BP

F2,6BP acceleratesPFK-1

Page 41: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-16

When glucose is low, so is F2,6BP

F2,6BP inhibitsFBPase

Page 42: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-16

When glucose is low, so is F2,6BPWhen glucose is abundant, so is F2,6BP

Page 43: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

pg 581

Page 44: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-17

Separate distinct enzyme activities control Fr2,6BP levels

Page 45: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-17

…and hormones control these enzymes

Page 46: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Glycogen: the glucose buffer…

Page 47: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Glycogen granules

~ 1600 glucose monomers per granule

Page 48: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 7-14

Page 49: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Glycogen in real life…

Page 50: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

How is glycogen synthesized?

-sequential addition of glucose to a growing a1-4 linked linear polymer

-creation of branches composed of a1-6 linkages

glycogenin, then glycogen synthase

branching enzyme

Page 51: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

O

1

23

4

5

6

reducingend

non-reducing

end

Glucose ends…

Page 52: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

polymer ends…

fig 7-14

Page 53: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

pg 597

Page 54: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-29

addition of UDP carrier to glucose-1-P

Page 55: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-30

addition of glucose monomersto the growing glycogen chain

Page 56: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-31

Glycogen branching enzyme creates branches

Page 57: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-9

Glycogen branching enzyme creates branches

10a1 4 3

7 a1 6

a1 4

Page 58: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

How is glycogen broken down?

-sequential removal of glucose-1P from the non-reducing end

-dismantling of those pesky branches

glycogen phosphorylase

debranching enzyme

Page 59: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 14-11

Page 60: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-26

debranching enzyme removes branches

Page 61: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

4

4 a1 6

a1 47a1 4

1 a1 6

7a1 4

freeglucose

Debranching enzyme removes branches

transferaseactivity

a1-6glucosidase

Page 62: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-36

Allosteric control of glycogen phosphorylase

Page 63: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Hormonal control of glycogen phosphorylase

fig 15-34

Page 64: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 15-37

regulation ofglycogen synthaseby phos-phorylationas well…

Page 65: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 23-13

Liver glucosemetabolism

Page 66: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Blood glucoselevel is criticaland stringentlyregulated

fig 23-23

Page 67: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 23-20

The Coricycle

Page 68: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Liver as a "glucostat"

high blood glucose

low blood glucose

Page 69: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Glucagon: the hormone of starvation

phosphorylation of enzymes

alteration of fructose 2,6 bis P

Page 70: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

Insulin: the hormone of plenty

Page 71: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +
Page 72: Pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD +

fig 23-24