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Tissues > T03 - Carbohydrate Metabolism II > Flashcards

T03 - Carbohydrate Metabolism II Flashcards

1
Q

The allosteric mode of regulation acts on what order of time?

A

milliseconds

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2
Q

The protein localization mode of regulation acts on what order of time?

A

seconds-minutes

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3
Q

The covalent modification mode of regulation acts on what order of time?

A

minutes

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4
Q

The gene expression mode of regulation acts on what order of time?

A

hours

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5
Q

Describe how the liver responds to high blood [glucose] levels.

A

liver uses GLUT2 transporter + glucokinase to detect and then stores excess glucose as glycogen

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6
Q

Describe how pancreatic beta cells respond to high blood [glucose] levels.

A

pancreatic beta cells use GLUT2 transporter to detect and then release insulin to lower blood [glucose]

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7
Q

Describe the interplay between insulin and glucagon in type 1 diabetes and the resulting effect.

A

insulin lacking and therefore glucagon chronically high, causing hyperglycemia

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8
Q

Describe the interplay between insulin and glucagon in type 2 diabetes and the resulting effect.

A

insulin signaling lacking (i.e. defect in receptor) and glucagon action is chronically high

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9
Q

What is the effect of glucagon?

A

raises blood [glucose]

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10
Q

(T/F) Glucose levels fluctuate significantly over the course of a day.

A

False. Glucose levels actually remain relatively constant, with fluctuations maxing at 5 mM.

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11
Q

(T/F) GLUT3 is only expressed in the brain.

A

False. It is expressed in most tissues, but is the predominant transporter in neurons, which is why it is designated as the “brain” glucose transporter.

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12
Q

Which of the four GLUT transporters are NOT expressed in all tissues?

A

GLUT2 (expressed in liver and pancreatic beta cells); GLUT4 (expressed in muscle and fat)

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13
Q

Which of the four GLUT transporters are insulin-dependent for activation?

A

GLUT4 only

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14
Q

Does glucose-6-phosphate inhibit hexokinase IV/glucokinase?

A

No.

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15
Q

Glucokinase is highly expressed in which tissues? (2)

A

liver; pancreatic beta cells

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16
Q

What is the significance of hexokinases I-III lacking a GK-RP form of regulation?

A

lack of GKRP-type regulation means that organs such as brain and muscle can use glucose even at low blood [glucose]

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17
Q

What are the key three reactions within glycolysis that are highly regulated?

A

glucose → G6P [hexokinase]

F6P → F-1,6-bP [PFK]

PEP → pyruvate [pyruvate kinase]

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18
Q

What is the major site of expression for hexokinase I?

A

brain (and many other tissues)

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19
Q

What is the major site of expression of hexokinase II? (2)

A

fat

muscle

20
Q

What is the major site of expression of hexokinase III?

A

lung

21
Q

What is the major site of expression of hexokinase IV? (2)

A

liver

islet beta cells of pancreas

22
Q

Draw a graph that shows relative enzyme activity for hexokinase and glucokinase.

A
23
Q

Which enzyme is thought to be the most important regulatory point for glycolysis?

A

PFK

24
Q

Why does H+ inhibit PFK?

A

H+ is associated with lactate production, which is a signal that there is already enough energy

25
Q

Which molecule is the most important regulator of PFK?

A

F-2,6-bP

26
Q

What are the two mechanisms by which F-2,6-bP upregulates PFK activity?

A

(1) F-2,6-bP antagonizes ATP inhibition of PFK
(2) lowers Km of enzyme for F6P, the PFK substrate (i.e. increases affinity)

27
Q

What is a bifunctional protein/enzyme? In what context is it used?

A

contains both kinase and phosphatase domains

used to interconvert F6P and F-2,6-bP

28
Q

How does the fasting state affect the bifunctional protein?

A

activates phosphatase function, which reduces F-2,6-bP and slows down glycolytic flux

29
Q

How does the feeding state affect the bifunctional protein?

A

activates kinase domain, which increases F-2,6-bP and increases glycolytic flux

30
Q

What are the activators and inhibitors of pyruvate kinase?

A

activated by F-1,6-bP

inhibited by ATP and alanine

31
Q

Describe the activity of HIF in normoxic conditions.

A

HIF is turned over as quickly as it’s made, mediated by binding of VHL (and is ultimately degraded by proteosome)

32
Q

Describe the activity of HIF in hypoxic conditions and the resulting effect on glycolysis.

A

HIF forms active heterodimer with ARNT and avoids degradation → HIF target genes are glycolytic enzymes (since glycosis doesn’t require O2)

in short, hypoxia means activation of glycolysis

33
Q

Describe the activity of HIF in cancer cells.

A

HIF is always active in many cancer cells (Warburg effect — cancer cells are highly glycolytic)

34
Q

What are the inhibitors of fructose-1,6-bisphosphatase?

A

F-2,6-bP

AMP

35
Q

What are the activators of fructose-1,6-bisphosphatase?

A

citrate

36
Q

What are the activators of the pyruvate kinase reaction?

A

F-1,6-bP

37
Q

What are the inhibitors of the pyruvate kinase reaction?

A

ATP

alanine

38
Q

What are the inhibitors of the PEP carboxykinase reaction?

A

ADP

39
Q

What are the activators of the pyruvate carboxylase reaction?

A

acetyl CoA

40
Q

What are the inhibitors of the pyruvate carboxylase reaction?

A

ADP

41
Q

Draw a diagram illustrating the reciprocal regulation of glycolysis and gluconeogenesis.

A
42
Q

What is the relationship between glucagon and PEP carboxykinase?

A

glucagon promotes transcription of PEP carboxykinase

43
Q

Draw a diagram showing how the phosphorylation/dephosphorylation of PFK works in normoglycemic and hypoglycemic conditions.

A
44
Q

What specific component of the HIF system is mutated in cancer cells that exhibit the Warburg effect?

A

prolyl hydroxylase is mutated → it can’t bind HIF → HIF accumulates → cell thinks it’s in hypoxia and therefore drives glycolysis

45
Q

HIF does not regulate the normal bifunctional enzyme. Describe how one of the isoforms of the bifunctional enzyme is regulated by HIF.

A

HIF regulates an isoform (iPFK-2) that has a mutation in the phosphatase domain → kinase domain always on → constitutive production of F-2,6-bP → high glycolytic rate as F-2,6-bP is an activator of PFK

Tissues (23 decks)

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