Glucose Transport and Phosphorylation Flashcards

1
Q

For glucose metabolism to occur the sugar must do what first?

A

Enter a cell

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2
Q

Can glucose alone diffuse across lipid membranes?

A

No, its polar

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3
Q

How does it get around the inability of glucose to be transported through the cell?

A

Bound to transport proteins

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4
Q

How is glucose entry facilitated?

A

Facilitated transport via glut transporters (I-5)

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5
Q

What are the two types of transport proteins on epithelial cells that transport glucose?

A

Sodium dependent, facilitative glucose transporters

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6
Q

Describe the structure of a facilitated glucose transporter.

A

12 transmembrane helices, the amino and carboxy terminals are cytoplasmic, family of five glucose transporters

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7
Q

What GLUT transporter is expressed on all tissues? Liver and pancreatic beta cells only? Muscle and fat cells? Small intestine?

A

1 and 3, 2, 4, 5

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8
Q

How does glucose bind its transport protein?

A

Via interaction with the transport proteins hydroxyl groups

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9
Q

What are signs of hypoglycemia?

A

18-54mg/dL blood sugar, lightheadedness, dizziness, coma

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10
Q

What is the only way glucose gets into brain?

A

Transport proteins

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11
Q

What enzyme phosporylates glucose once it enters the cell?

A

Hexokinase I-IV depending on location, forms glc-6-phosphate which is a branch point for many pathways

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12
Q

What is the function of glycolysis? Pentose phosphate pathway? Glycogen synthesis?

A

Source of ATP; NADPH and ribose precursors; storage of glucose

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13
Q

Why do we phosphorylate glucose once its taken up?

A

Activates glucose for metabolism; keeps glc within cell can’t be transported back out; determines direction of glc metabolism

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14
Q

What enzyme removes the phosphate on G6P?

A

Glucose 6 phosphatase (irreversible rxn. ; found in liver and kidney not in muscle)

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15
Q

What is different about HK IV? Aka glucokinase?

A

Higher Km, therefore lower affinity, therefore takes higher conc. Of glucose to alter its activity (reaction velocity)  better regulatory control of glucose in liver

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16
Q

Where is glucose 6 phosphatase found? (organs)

A

Liver and kidney, NOT MUSCLE

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17
Q

What cellular compartment is glucose 6 phosphatase found?

A

ER

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18
Q

Where are CHO converted to glucose, galactose, and fructose?

A

intestinal tract

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19
Q

T/F galactose and fructose are converted to glucose or glucose intermediates

A

True

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20
Q

What molecule is a branch point for several metabolic pathways and allows for glucose entry and phosphorylation? Can this molecule be transported out of the cell?

A

G-6-P

No

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21
Q

When ATP reaches a threshold, what process occurs?

A

glycogenesis

22
Q

How does glucose enter a cell?

A

absorption by intestinal epithelium via GLUT-5 transporters after CHO broken down to monosaccharides

23
Q

Why can glucose not diffuse across the hydrophobic phospholipid bilayer? How does it cross

A
  • it is polar

- glucose binds to transport proteins

24
Q

What are the 2 types of transport proteins in intestinal epithelial cells?

A
  1. Na dependent glucose transporter (usually luminal side of intestinal epithelia)
  2. Facilitative glucose transporter (usually at basal membrane) => GLUT transporters
25
Q

Which glucose transporter is a symporter? How does this help glucose?

A
  • Na dependent glucose transporter

- enables cells to transport glucose against its concentration gradient

26
Q

T/F Glucose and Na are coupled so transport can occur in a concentration from low to high direction

A

False, Na/K pumps keep intracellular Na low so Na moves from high to low while glucose moves from low to high concentrations

27
Q

Describe the function of GLUT transporters (facilitative glucose transporters)

A
  1. move glucose from high to low concentration
  2. Proteins contain 12 transmembrane alpha helices
  3. Both N and C terminus
28
Q

Describe GLUT 1 WRT location, KM, comments

A

location=> all mammalian tissues
Km=> 1mM
Comments=> basal glucose uptake

29
Q

Describe GLUT 2 WRT location, KM, comments

A

location=> liver and pancreatic B cells
Km=> 15-20 Km
comments=> in pancreas-plays a role in regulation of insulin
-in liver, removes excess glucose from blood

30
Q

Describe GLUT 3 WRT location, KM, comments

A

location=> neuronal cells and all mammalian tissues
Km=>1mM
Comments=> basal glucose uptake

31
Q

Describe GLUT 4 WRT location, KM, comments

A

location=> muscle, fat cells
Km=> 5mM
comments=> amount in muscle plasma membrane increases with endurance training

32
Q

Describe GLUT 5 WRT location, KM, comments

A

location=> small intestine

comments=> primarily a fructose transporter

33
Q

Glucose binds to the transport protein via what?

A

interactions with its hydroxyl groups undergoes a conformational change

34
Q

What GLUT is found in RBC?

A

GLUT 1

35
Q

How is glucose transport increased in muscle and adipose tissue?

A

Insulin stimulate recruitment of GLUT 4 to the membrane

36
Q

Describe GLUT 2 found in the liver

A
  • Km is high as the important fxn of liver is to maintain blood glucose levels
  • liver will convert glucose to other energy storage molecules only when blood glucose is high
37
Q

Describe GLUT 2 in pancreas

A

-stimulates glucose uptake in pancreatic B cells
- metabolized via glycolysis generating ATP resulting in elevated ATP/ADP ratio in cells
RESULTS: INCREASE IN CYTOSOLIC Ca that triggers fusion of insulin containing vesicles with plasma membrane releasing insulin

38
Q

What occurs when glucose transport is disrupted through the blood-brain barrier?

A
  • hypoglycemia
  • Sx decreased supply of glucose to brain-lightheadedness, dizziness, coma
  • Due to slow rate of glucose transport through blood brain barrier
39
Q

What GLUT is present between the blood brain barrier?

A

GLUT 1 transporters

40
Q

Describe the 5 characteristics of neural GLUT 1 transporters

A
  1. tight jxns bw endothelial cells
  2. narrow intercellular space
  3. lack of pinocytosis
  4. continuous basement membrane
  5. glucose transporters in both membranes
41
Q

What occurs once glucose enters a cell? How does glucose enter a number of different metabolic pathways?

A
  • phosphorylation by one of hexokinase isozymes

- phosphorylation of glucose into G-6-P

42
Q

What are the 3 pathways G-6-P is used in?

A
  • glycolysis (source of ATP for cells)
  • pentose phosphate pathway (source of NADPH)
  • glycogen synthesis (storage polymer of glucose when ATP is elevated)
43
Q

What are the fxns of glucose phosphorylation?

A
  1. controls amount of glucose taken up by cells
  2. activates glucose for further metabolism
  3. keeps glucose within cell since G-6-P cannot be transported across plasma membrane
  4. determine direction of glucose metabolism
44
Q

Describe how G-6-P can be converted back to glucose

A

Glucose-6-phosphatase that is only expressed in liver and kidney

45
Q

What catalyzes the first step in glucose metabolism? What is the result?

A

hexokinases

RESULT: transfer of phosphate from ATP to glucose resulting in G-6-P

46
Q

Describe HK I-III wrt tissue distribution, Km for glucose, regulation

A

tissue distribution=> all cells
Km => 0.1 mM or lower
Regulation (end product) => inhibited by G-6-P (glucose not phosphorylated by cell unless G-6-P is utilized in a metabolic path)

47
Q

Describe HK IV or glucokinase (GK) wrt tissue distribution, Km for glucose, regulation

A

tissue distribution=> Liver, Beta cells of pancreas
Km=> 10-20 mM (lower in fasting)
regulation=> induced by insulin

48
Q

What is the last step of glycogenolysis and gluconeogenesis?

A

G-6-Pase

49
Q

What are characteristics of G-6-Pase?

A
  • irreversible rxn
  • allows reversal of GK rxn
  • essential for hepatic control of blood glucose
  • FOUND IN LIVER AND KIDNEY ONLY
  • membrane-assoc. enzyme complex found in ER
50
Q

What transporter is used at basal glucose levels?

A

GLUT 1

51
Q

What transporter is used when glucose is high? what are the results?

A

GLUT 2 which results in insulin being released with fuses with plasma membrane at certain levels