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Flashcards in Metabolic regulation Deck (60):
1

glucose and intracellular ATP maintaine at ___mM to maintain homeostasis

5

2

Hexokinase is an ____which catalyze the same reaction although they have slightly different properties. Made from different genes with diff regulatory aspects.

isoenzyme

3

ATP, ADP and AMP bind to ___enzymes and change their activity level. They are examples of ____modifiers

regulatory; allosteric

4

Covalent modification is

phosphorolation

5

What is a futile pathway

ATP is hydrolyzed and nothing is gained when glycolyis and gluconeogenis is happening at the same time. So they are reciprocally regulated

6

Glucose gets into cell via ___

GLUT 4

7

GLUT 4 is ___dependent

insulin; otherwise sequestered internally in vesicles

8

What are 3 points of regulation for glycolysis

1. Hexokinase
2. Phosphofructokinase 1
3. Pyruvate kinase

9

What are 3 points of regulation for gluconeogenesis

1. Glucose 6-phosphatase
2. Fructose-1, 6-bisphosphatase
3. Pyruvate carboxylase + PEP carboxykinase

10

Glucokinase is liver specific____

isozyme; will forgoe glucose to make sure brain has enough.

11

Hexokinase 4 is sequestered in ____when glucose concentration is low.

nucleus. Cant encounter glucose and phosphorolate it so its kept in cell.

12

When glucose levels are ____ it binds to hexokinase 4 and releases it from the nucleus so it can start phosphorolating glucose so that it can be stored as glycogen

high

13

PFK 1 in glycolysis is an ____regulator

allosteric

14

High [ATP] and [citrate] allosterically signal that energy needs are met and inhibit:

PFK-1

15

High [ADP] and [AMP] allosterically signal need for ATP production and activate ____ and inhibit ___

PFK-1; FBPase-1

16

In the liver, the most important allosteric regulator of PFK-1 is _____ which is synthesized by _____

fructose, 2-6 bisphosphate; PFK-2

17

Glycogen stores in muscle can't help maintain blood glucose levels bc it is never:

released. Doesn't have glucose 6 phosphatase. Only uses glycogen for itself

18

Muscles have _____ receptors but no ____receptors; therefore it does not produce the enzymes for gluconeogenesis.

epinephrine; glucagon

19

What are the 3 principle hormones of fuel metabolixm

1. insulin: fed
2. glucagon: hungry
3. epinephrine: terrified

20

Where does epinephrine come form

adrenal medulla; its actually a catacholamine

21

What is a phenol ring with two hydroxyl groups called

catecolamine. Derived directly from aa - tyrosine; have cell membrane associated receptors and trigger a second messenger

22

What is the classical second messenger

cyclic AMP

23

Where does glucagon come from

alpha cells of pancreas-->islets of Langerhaans

24

Pancreas has ___ and ___ functions

exocrine: digestive enzymes
endocrine: releases proteins into bloodstream so it can go throughout the body

25

Beta cells make

insulin

26

Glucagon is a ____hormone

protein

27

What are the targets of glucagon and epinephrine

Use cyclic amp signaling to change metabolic activity.

28

What is a serpentine receptor

External ligand binding to receptor activates an intracellular GTP binding protein which regulates an enzyme that generates an intracellular second messenger. Go back and forth across cell membrane and when hormone binds it activates G protein

29

What are the 5 proteins involved in epinephrine and glucagon signaling

1. beta adrenergic receptor/glucagon receptor
2. Gs protein
3. adenylate cyclase
4. protein kinase A
5. cyclic nucletodie phosphodiesterase

30

1. Epeniphrine binds its specific receptor -->changes conformation of receptor site and G protein. When receptor binds it knocks off ___ and GTP associates. Alpha subunit loses affinity for its receptor and moves into cell membrane and binds to target enzyme: ______GDP falls off and GTP binds. Now has high affinity for target enzyme.

GDP; adenylate cyclase

31

What is adenylate cyclase

the enzyme that converts ATP to cyclic AMP

32

Protein Kinase A becomes activated by ____and changes metabolic activity of all of its protein targets by:

cyclic AMP; phosphorlation

33

What are ways to self limit this process?

1. G protein has inherent GTPase function: hydrolyze GTP, converts it to GDP which now has affinity for the receptor and its beta and gamma subunits. Moves back into its original position.
2. cAMP doesnt hang around all day. Cyclic nucleotide phosphodiesterase hydrolizes cAMP and inactivates it

34

cAMP phosphodiesterase is inhibited by:

caffeine and theophylline

35

How is protein Kinase A activated; what does it catalyze

cAMP; catalyzes the phosphorylation of target proteins

36

Insulin DOES NOT produce ____as a secondary messenger

cAMP

37

What are C peptides indicative of

diagnostic tool that tells you if your body makes natural insulin and differentiates between Type 1 and Type 2 diabetes

38

Which aa form disulfide bonds?

cysteine

39

Insulin receptors come from:

receptor tyrosine kinases
"RTK"; cell signaling proliferation and growth

40

3 aa that have hydroxyl groups:

1. serine
2. threonine
3. tyrosine

41

What do insulin receptors do

Auto phosphoralates its own tyrosine receptors that activates receptor and other targets.

42

How does insulin signaling I occur

1. Insulin binds to receptor and autophosphorolates on its own tyrosine residues
2.

43

Growth factors cause

cell proliferation

44

Insulin is a potent ___factor that activates the ____pathway

growth; MAPK --> regulate transcription factors needed for cell division

45

What is Ras

G protein; when GDP bound its inactive when GTP bound it activates Raf 1 Kinase that starts MAPK cascade that turns on genes for cell division.

46

Ras is commonly _____in different cancers.

mutated. -->in GTPase domain; the part that is meant to turn off the singal. Cell keeps dividing

47

IRS 1 can interact with

multiple targets.

48

How does insulin signaling II occur

PKB activated by IRS1, which leads to phosphoprotein phosophatase 1 which takes phosophate group off that protein kinase A phosphorolates.

49

What is the major modulator for PFK-1

Fructose 2,6 bisphosphate; allosterically increases PFK-1 affinity for F-6-P (fructose 6 phosphate); decreases PFK-1 affinity for ATP and citrate

50

PFK-1 activation favors

glycolysis

51

Active PFK-2, means there is a high amount of Fructose, 2-6 BP which activates ____ and favors___

PFK1; glycolysis

52

If PFK-2 gets phosphorolated it becomes ___

inactivated; glycolysis would stop and gluconeogenesis would happen

53

PFK-2 is a ____enzyme

bifunctional; also takes phosphate back off.

54

What does pyruvate kinase do in glycolysis

Converts PEP to pyruvate and makes ATP; this is the first step thats irreversible in gluconeogenesis

55

If ATP levels are high glycolysis:

slows down

56

if ADP and AMP are high

we will need to make more ATP

57

Liver has special isoenzyme of pyruvate kinase that is inactivated by_____. When blood glucose falls, ______is secreted. _____ levels increase. ____is activated. PFK-2 is phosphorolated and inactivated. _______ decreases; _____ activity decreases. Glycolysis slows down. Pyruvate kinase is _____ and inactivated.

PKA phosphorolation; glucagon; cAMP; PKA is activated; Fructose 2, 6 BP; PFK-1; phosphorolated.

58

Gluconeogenesis is favored in the

liver

59

pyruvate carboxylase is activated by

acetyl coA

60

High levels of insulin blocks the transcription of

PEPCK; thus reducing gluconeogenesis.