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18' DEMS > 🔸 Glycolysis and TCA Cycle > Flashcards

🔸 Glycolysis and TCA Cycle Flashcards

1
Q

What determines the direction through the pathway (e.g., why glycolysis and not gluconeogenesis)?

A

Regulation of enzymes

Position of molecules (because molecular trapping can drive direction)

Investment of energy

Rate-limiting steps

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2
Q

Glycolysis begins with _________.

A

glucose being phosphorylated to glucose-6-phosphate in the cytosol (representing energy investment and molecular trapping)

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3
Q

Per Dr. Benessen, what are the three “key” regulatory steps in glycolysis?

A

(1) Glucose to glucose-6-phosphate
(2) Fructose-6-phosphate to fructose-1,6-bisphosphate rate-limiting
(3) Phosphoenolpyruvate to pyruvate

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4
Q

What is the key regulated step in the TCA cycle?

A

Pyruvate to acetyl co-a (via loss of CO2)

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5
Q

Citrate performs what function?

A

It is a negative feedback signal.

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6
Q

What does the TCA cycle make?

A

GTP
NADH
FADH2

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7
Q

The precursor that binds to acetyl co-a is _________.

A

oxaloacetate

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8
Q

Pyruvate to glucose is ___________.

A

gluconeogenesis

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9
Q

The three steps that are regulated in gluconeogenesis are __________.

A

the same that are regulated in glycolysis

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10
Q

The first step that differs between glycolysis and glycogen formation is ___________.

A

glucose-6-phosphate is isomerized to glucose-1-phosphate

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11
Q

What is the precursor molecule immediately before glycogen?

A

UDP-glucose

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12
Q

The regulatory step in glycogen formation is ___________.

A

UDP-glucose to glycogen

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13
Q

The regulatory step in glycogen breakdown is ___________.

A

glycogen to glucose-1-phosphate

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14
Q

HMS is ____________.

A

hexose monophosphate shunt

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15
Q

HMS forms ________ from glucose in states of excess (when glycogen stores are maxed out).

A

ribose (for purines/pyrimidines) and..

NADPH (energy for synthetic reactions, e.g. fat synthesis)

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16
Q

Gluconeogenesis has a funny step in the mitochondria, in which ______________.

A

pyruvate → oxaloacetate → phosphoenolpyruvate

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17
Q

The TCA cycle is primarily substrate driven, meaning ______________.

A

consumption of ATP drives more production.

(through the TCA cycle itself)

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18
Q

What two cell types use glycolysis as their primary energy source?

A

RBCs and sperm

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19
Q

List the reactants in the glycolysis pathway.

A 
•Glucose
(Hexokinase or glucokinase) 
•Glucose 6-phosphate 
•Fructose 6-phosphate
(Phosphofructokinase) 
•Fructose 1,6-bisphosphate
(Aldolase)
•Glyceraldehyde 3-phosphate
(Glyceraldehye 3-phosphate dehydrogenase) 
•1,3-Bisphosphoglycerate x2
•3-Phosphoglycerate x2
•2-Phosphoglycerate x2
•Phosphoenolpyruvate x2
•Pyruvate x2
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20
Q

What are the two classic tissues that are insulin sensitive?

A

Skeletal muscle and adipose tissue

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21
Q

The insulin-inducible glucose channel is ____________, while the constitutive glucose channel is __________.

A

GLUT4; GLUT2

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22
Q

What is substrate-level phosphorylation?

A

Phosphorylation of ADP to ATP by enzymes in the TCA

oxidative phosphorylation is use of ATP synthase and H+ gradient

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23
Q

What three things are accomplished by the initial phosphorylation of glucose?

A

(1) Glucose gets trapped in cell.
(2) Glucose stores energy and is more able to move to next step in glycolysis.
(3) The enzyme that next handles glucose interacts with the phosphate group and the “Ea” is lowered.

24
Q

Hexokinase is present in _____________, while glucokinase is present in _____________.

A

all tissues;

the liver and pancreatic β-cells

25
Q

Why is it favorable to have glucokinase in the liver?

A
  • Glucokinase has a higher Km than hexokinase → When glucose is high, the liver can phosphorylate more glucose than other tissues→ this traps glucose in hepatocytes to be stored as glycogen.
  • Similarly, when glucose is low, less glucose is phosphorylated in hepatocytes and the liver thus releases glucose.
26
Q

True or false:

phosphorylation of glucose and fructose 6-phosphate are reversible reactions.

A

False.

Both are irreversible.

27
Q

Phosphofructokinase is allosterically inhibited by _______________ and stimulated by __________.

A

ATP and citrate;

AMP

28
Q

Don’t forget PFK-2 is bidirectional. Under the high-insulin, low-glucagon (fed) state, describe what happens to the PKA PFK-2 pathway.

A

There is low PKA activity because of ↓cAMP. PKA normally phosphorylates (thus deactivates) PFK-2. Thus, ↓PKA activity leads to ↑PFK-2. PFK-2 creates fructose 2,6-bisphosphate, which potently activates PFK-1 and stimulates glycolysis.

29
Q

_____________ is the most potent activator of PFK-1.

A

Fructose 2,6-bisphosphate

this can activate PFK-1 even when ATP is high

30
Q

Fructose 2,6-bisphosphate inhibits _____________.

A

fructose 1,6-bisphosphatase (an important enzyme in gluconeogenesis)

31
Q

Don’t forget PFK-2 is bidirectional. When glucagon is high and insulin is low, PKA is […]. what is the result?

A

PKA is activated and will phosphorylate PFK-2.

The phosphorylated form is a phosphatase that removes the 2-phosphate from fructose.

32
Q

What is important to remember about the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase?

A

It is the first to create NADH in glycolysis!

33
Q

What is noteworthy about the reaction 1,3-bisphosphoglycerate (x1) to 3-phosphoglycerate (x2)?

A

It is the first reaction to produce ATP;

it produces two molecules of it, and thus brings the net ATP to zero.

34
Q

What enzyme catalyzes the first reaction to have substrate-level phosphorylation in glycolysis?

A

Phosphoglycerate kinase (being the reaction from 1,3-bisphosphoglycerate to two molecules of 3-phosphoglycerate)

35
Q

The first enzyme to produce net positive ATP from glycolysis is ____________.

A

pyruvate kinase (bringing the total to +2 molecules of ATP)

36
Q

What stimulates the reaction catalyzed by pyruvate kinase?

A

fructose 1,6-bisphosphate

37
Q

What inhibits pyruvate kinase?

A

ATP and protein kinase A (by phosphorylating it)

38
Q

During fasting, the body wants to turn off _________ and turn on _____________.

A

glycolysis; gluconeogenesis

39
Q

In the presence of _______, pyruvate will be converted to acetyl co-a.

A

oxygen

40
Q

Why is pyruvate converted to lactic acid?

A
  • Because this oxidizes NADH to NAD+.

* We need NAD+ to oxidize glyceraldehyde 3-phosphate to 1,3-bisphosphate.

41
Q

Why do the liver and heart convert lactate to pyruvate?

A

Because the NADH/NAD+ ratio is much lower, driving the conversion of lactate to pyruvate, which can go into the TCA cycle and generate CO2, H2O, and ATP.

42
Q

In the fed state, pyruvate can be converted to ___________.

A

alanine for protein synthesis or fatty acid synthesis

43
Q

What happens to pyruvate in the liver during a fasting state?

A

It is converted to oxaloacetate for substrates for gluconeogenesis.

44
Q

True or false: pyruvate gets converted to acetyl co-a in the cytosol.

A

False. Pyruvate dehydrogenase is in the mitochondria.

45
Q

What things inhibit pyruvate dehydrogenase?

A

NADH and acetyl co-a (the immediate product and a downstream product)

46
Q

Why does thiamine deficiency lead to neurologic symptoms?

A

Because pyruvate oxidation is crucial for brain function, and thiamine is a cofactor for this reaction.

47
Q

High levels of _______________ in the blood are diagnostic of thiamine deficiency.

A

pyruvate

48
Q

What organ needs to inhibit pyruvate dehydrogenase?

A

The liver, so that pyruvate can be re-directed to gluconeogenesis

49
Q

Remember what Dr. Bessesen says: in the fed state, insulins causes proteins to be _____________.

A

dephosphorylated

50
Q

Pyruvate dehydrogenase is active when ________________ (a covalent modification).

A

dephosphorylated

51
Q

The enzyme that inhibits pyruvate dehydrogenase is stimulated by _______________ and inhibited by _____________.

A

ATP; pyruvate

52
Q

What enzyme catalyzes the first reaction of the TCA cycle?

A

Citrate synthase, which unites oxaloacetate and acetyl co-a

53
Q

Citrate is a feedback inhibitor of _______.

A

PFK1

54
Q

List the substrates and enzymes of the TCA cycle.

A

Oxaloacetate + acetyl co-a
(Citrate synthase)
Citrate
(Aconitase)
Isocitrate
(Isocitrate dehydrogenase) CO2 an NADH produced
Alpha-ketoglutarate
(Alpha-ketoglutarate dehydrogenase) CO2 and NADH produced
Succinyl co-a
(Succinate thiokinase) GTP produced
Succinate
(Succinate dehydrogenase) FADH2 produced
Fumarate
(Fumarase)
Malate
(Malate dehydrogenase) NADH produced
Oxaloacetate

55
Q

Amino acids typically enter the TCA cycle at _____________.

A

alpha-ketoglutarate, succinyl co-a, or fumarate

56
Q

What would occur without the NAD+ generated from the pyruvate to lactate conversion?

A

glycolysis would stop and the cell would be totally without energy sources.

18' DEMS (133 decks)

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