Lecture 16: Carbohydrate Metabolism Flashcards

1
Q

Gluconeogensis

A

provides gluccose
reciprocal regulation
Cori Cycle

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2
Q

reciprocal regulation

A

different directions
Glycolysis regulated by PFK1
Gluconeogenesis regulated by f16BPase

all controlled by allosteric regulator F2-6BP, energy charge, and citrate levles

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3
Q

Cori Cycle overview

A

recycle lactate
export lactate to liver
convert it to pyruvate
synth glucose by gluconeogenesis

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4
Q

What does gluconeogensis accomplish?

A

liver and kidney cells
make glucose from non carbo sources like glycerol, a.a.s lactate, etc

plants use it to make GAP glucose

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5
Q

how many ATP needed for glucconeogenesis

A

4 ATP
2 GTP
2 NADH

SIX ATP

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6
Q

key enzymes?

A

pyruvate carboxylase: convert pyruvate to OAA (ALSO IN CITRATE CYCLE)

responsible for just gluconeo
PEPCK: OAA to PEP
FBPase-1 (1,6 BPase) catalyze dephosphylation of fructose to make fructose 6P
Glucose 6PL catalyzes dephosphory of G6P to make glucose

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7
Q

Glycolysis and gluconeogensis…

A

OPPOSING PATHWAYS

so substrate concs dictate what direction reactions run

EXCEPT for specific pathways that use specific enzymes

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8
Q

examples of bypass enzymes in gluconeogenesis that reverse the glycolysis reaction

A

Fructose 1,6 BPase

G6P

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9
Q

Net ATP from glycolysis

A

2

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10
Q

What if we ran glycolysis and gluconeogensis at the same time ??

A

We would use 4 ATP if we ran glycolysis and gluconeogensis at the same time

(you get 2 from glycolysis, but we burn through 6 in gluconeogenesis, meaning we burn through 4 ATP total if run at same time)

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11
Q

SO why is it important that pathways are regulated?

A

don’t want to waste ATP!

So don’t want to run glycolysis and gluconeogensis at the same time

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12
Q

Glycolytic and gluconeogenic pathways are very regulated. How?

A

Energy charge, acetyl CoA, citrate, alanine are metabolites

F-2, 6 BP is reciprocal regulator

all act on opposing enzymes in pathways

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13
Q

Glycolysis inhibitors

A

ATP

citrate

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14
Q

Glycolysis stimulators

A

F-2,6 BP

AMP

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15
Q

Gluconeogenesis inhibitors

A

F-2,6 BP

AMP

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16
Q

Gluconeogenesis stimulators

A

citrate

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17
Q

pyruvate kinase inhibitors

A

(regulates glycolysis) (takes pyruvate to OAA)
ATP
Alanine

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18
Q

pyruvate kinase stimulators

A

(regulates glycolysis)

F-2,6 BP

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19
Q

PEPCK inhibitors

A

ADP (regulates Gluconeogenesis)

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20
Q

Pyruvate carboxylase inhibitors

A

(regulates Gluconeogenesis)

ADP

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21
Q

Pyruvate carboxylase stimulators

A

(regulates Gluconeogenesis)

Acetyl CoA

22
Q

Why do we consider the reactions regulated by Pyruvate carboxylase and PEPCK a cost of 4 ATP to convert pyruvate to PEP when we count up the # of ATP needed to generate 1 glucose from 2 pyruvate

A

We have to run the pair of reactions twice!
if we are making glucose, we need SIX carbons, that means we need TWO pyruvates. Each time, this takes 2 ATP (total of 4)

23
Q

why do we count GTP as an ATP

A

because there is no free nrg change to interconvert ATP and GTP

24
Q

pyruvate carboxylase

A

pyruvate to OAA, its modified to do this rxn
lysine residue
long swinging arm between the two active sites of the enzyme

25
Q

where have we seen this enzymatic reaction before? (its activated by acetyl CoA and generates OAA)

A

citrate cycle!!!!

its activated by acetyl CoA

26
Q

where is this all taking place???

A

pyruvate to OAA happens in matrix

all of the rest of glycolysis and gluconeogenesis happens in the cytosol

27
Q

so how does OAA get to cytosol?

A

OAA is converted to malate to leave the matrix and go to the cytosol

NADH NEEDED

malate goes back to OAA once it gets to matrix

28
Q

glyceraldehyde 3P dehydrogenase

A

NADH is given to it in glycolysis

OPPOSITE OF when there is NAD+ in the cytosol and NADH needs to be regernated during GLYCOLYSIS

29
Q

Reciprocal regulation definition

A

levels of metabolites inhibit one enzyme and stimulate another

30
Q

F-2BP

A

NOT a metabolite
JUST A REGULATOR of PFK1 and PBPase-1
substrate is glucose 6- phoshpate

31
Q

What is the metabolic logic of reciprocal regulation by citrate?

A

lots of citrate that we don’t need to make more nrg
so we start making glucose instead
turn on and off 2 pathways with same metabolite=no waste of nrg

32
Q

Does high F-2,6 BP activate or inhibit flux through the glycolytic pathway

A

activates

33
Q

Presence of F-2,6BP and PFK-1

A

when it is present, it takes a lot less activity to reach half max activity
when absent, it takes a lot more substrate to reach half max

25X times higher affinity of PFK1 for its substrate when F-2,6 BP is present

34
Q

Presence of F-2,6BP and FBPase-1

A

substrate of FBP-ase 1 is fructose bisphosphate

when F-2,6BP present, it takes more enzume to make half max activity: substate affinity is 15X lower

35
Q

Does low F-2,6 BP activate or inhibit flux through the gluconeogenic pathway?

A

ACTIVATES

36
Q

how is amount of F-2,6BP controlled?

A

by dual function enzyme PFK-2/FBase-2

it has TWO active sites

37
Q

Is PFK-2/FBase-2 one protein with 2 catalytic activities, or two proein subunits that form one quatenary complex

A

one protein with 2 catalytic actibities
its one polypep chain
center part connects them
the activity of one domain INHIBITS the activity of the other

38
Q

Glucagon signaling and PFK-2/FBase-2

A

stimulates phosphorylation of the enzyme (Through protein kinase a–PKA)
ACTIVATION of FBP-ase 2 domain

39
Q

Insulin signaling of PFK-2/FBase-2

A

stimulates dephosphorylation of enzyme

ACTIVATION of PFK-2 domain

40
Q

low blood sugar

A

glucagon signals
activate protein kinase a
phosphorylates one of PFK-2/FBase-2 domains: inactivates PFK-2 domain
FBP-ase 2 activated
fructose 6 phospate made from fructose bisposphate
more active gluconeogenesis

41
Q

high blood sugar

A
insulin signals
activate protein phosphatase one
actviates PFK-2 domain (dephosphorylate the domains)
catalyze to make fructose bisphosphate
more active glycolysis
42
Q

low blood sugar… whats active/not

A

glycolysus LESS active

gluconeogenesis MORE active

43
Q

high blood sugar…whats active/not

A

glycolysis MORE active

gluconeogenesis LESS active

44
Q

so what does level of F-2,6 BP do?

A

recipricoally regulate the enzymes
lots of one activates one pathway
lost of other activates other pathway
inhibits whats not active

45
Q

phosphorylating glucose with hexokinase does what

A

traps glucose in the cell

46
Q

but what about glucose 6P?

A

it can be imported into the ER and is dephosphorylayed
levels lumen
goes out of cell for use elsewhere

47
Q

Cori cycle

A
what happens to lactate made by anerobic muscle ativity
lactate goes to liver (gluconeogenesis)
liver converts it back to pyruvate
NADH produced (can be used by GAP)
pyruvate can go back to glucose
48
Q

so whats the point of the cori cycle??

A

a way we can keep doing glycolysis to get nrg from muscle cells

seperate locations for these pathways. happen in different tissues

49
Q

Cori cycle cost

A

4 ATP

50
Q

Explain why the Cori cycle has a net cost of 4 ATP to the organism?

A

we produce 2 ATP in skeletal muscle

costs 6 ATP in the liver

51
Q

so why do we do the Cori cycle if it costs 4 ATP?

A

if muscles need nrg, you have to get it somehow

52
Q

why do altheletes warm down?

A

enhances circulation

lactate can be cleared from muscles and used in liver for glucose synth via cori cycle