Glucose Transport and Phosphorylation Flashcards
For glucose metabolism to occur the sugar must do what first?
Enter a cell
Can glucose alone diffuse across lipid membranes?
No, its polar
How does it get around the inability of glucose to be transported through the cell?
Bound to transport proteins
How is glucose entry facilitated?
Facilitated transport via glut transporters (I-5)
What are the two types of transport proteins on epithelial cells that transport glucose?
Sodium dependent, facilitative glucose transporters
Describe the structure of a facilitated glucose transporter.
12 transmembrane helices, the amino and carboxy terminals are cytoplasmic, family of five glucose transporters
What GLUT transporter is expressed on all tissues? Liver and pancreatic beta cells only? Muscle and fat cells? Small intestine?
1 and 3, 2, 4, 5
How does glucose bind its transport protein?
Via interaction with the transport proteins hydroxyl groups
What are signs of hypoglycemia?
18-54mg/dL blood sugar, lightheadedness, dizziness, coma
What is the only way glucose gets into brain?
Transport proteins
What enzyme phosporylates glucose once it enters the cell?
Hexokinase I-IV depending on location, forms glc-6-phosphate which is a branch point for many pathways
What is the function of glycolysis? Pentose phosphate pathway? Glycogen synthesis?
Source of ATP; NADPH and ribose precursors; storage of glucose
Why do we phosphorylate glucose once its taken up?
Activates glucose for metabolism; keeps glc within cell can’t be transported back out; determines direction of glc metabolism
What enzyme removes the phosphate on G6P?
Glucose 6 phosphatase (irreversible rxn. ; found in liver and kidney not in muscle)
What is different about HK IV? Aka glucokinase?
Higher Km, therefore lower affinity, therefore takes higher conc. Of glucose to alter its activity (reaction velocity) better regulatory control of glucose in liver
Where is glucose 6 phosphatase found? (organs)
Liver and kidney, NOT MUSCLE
What cellular compartment is glucose 6 phosphatase found?
ER
Where are CHO converted to glucose, galactose, and fructose?
intestinal tract
T/F galactose and fructose are converted to glucose or glucose intermediates
True
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?
G-6-P
No
When ATP reaches a threshold, what process occurs?
glycogenesis
How does glucose enter a cell?
absorption by intestinal epithelium via GLUT-5 transporters after CHO broken down to monosaccharides
Why can glucose not diffuse across the hydrophobic phospholipid bilayer? How does it cross
- it is polar
- glucose binds to transport proteins
What are the 2 types of transport proteins in intestinal epithelial cells?
- Na dependent glucose transporter (usually luminal side of intestinal epithelia)
- Facilitative glucose transporter (usually at basal membrane) => GLUT transporters
Which glucose transporter is a symporter? How does this help glucose?
- Na dependent glucose transporter
- enables cells to transport glucose against its concentration gradient
T/F Glucose and Na are coupled so transport can occur in a concentration from low to high direction
False, Na/K pumps keep intracellular Na low so Na moves from high to low while glucose moves from low to high concentrations
Describe the function of GLUT transporters (facilitative glucose transporters)
- move glucose from high to low concentration
- Proteins contain 12 transmembrane alpha helices
- Both N and C terminus
Describe GLUT 1 WRT location, KM, comments
location=> all mammalian tissues
Km=> 1mM
Comments=> basal glucose uptake
Describe GLUT 2 WRT location, KM, comments
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
Describe GLUT 3 WRT location, KM, comments
location=> neuronal cells and all mammalian tissues
Km=>1mM
Comments=> basal glucose uptake
Describe GLUT 4 WRT location, KM, comments
location=> muscle, fat cells
Km=> 5mM
comments=> amount in muscle plasma membrane increases with endurance training
Describe GLUT 5 WRT location, KM, comments
location=> small intestine
comments=> primarily a fructose transporter
Glucose binds to the transport protein via what?
interactions with its hydroxyl groups undergoes a conformational change
What GLUT is found in RBC?
GLUT 1
How is glucose transport increased in muscle and adipose tissue?
Insulin stimulate recruitment of GLUT 4 to the membrane
Describe GLUT 2 found in the liver
- 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
Describe GLUT 2 in pancreas
-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
What occurs when glucose transport is disrupted through the blood-brain barrier?
- hypoglycemia
- Sx decreased supply of glucose to brain-lightheadedness, dizziness, coma
- Due to slow rate of glucose transport through blood brain barrier
What GLUT is present between the blood brain barrier?
GLUT 1 transporters
Describe the 5 characteristics of neural GLUT 1 transporters
- tight jxns bw endothelial cells
- narrow intercellular space
- lack of pinocytosis
- continuous basement membrane
- glucose transporters in both membranes
What occurs once glucose enters a cell? How does glucose enter a number of different metabolic pathways?
- phosphorylation by one of hexokinase isozymes
- phosphorylation of glucose into G-6-P
What are the 3 pathways G-6-P is used in?
- glycolysis (source of ATP for cells)
- pentose phosphate pathway (source of NADPH)
- glycogen synthesis (storage polymer of glucose when ATP is elevated)
What are the fxns of glucose phosphorylation?
- controls amount of glucose taken up by cells
- activates glucose for further metabolism
- keeps glucose within cell since G-6-P cannot be transported across plasma membrane
- determine direction of glucose metabolism
Describe how G-6-P can be converted back to glucose
Glucose-6-phosphatase that is only expressed in liver and kidney
What catalyzes the first step in glucose metabolism? What is the result?
hexokinases
RESULT: transfer of phosphate from ATP to glucose resulting in G-6-P
Describe HK I-III wrt tissue distribution, Km for glucose, regulation
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)
Describe HK IV or glucokinase (GK) wrt tissue distribution, Km for glucose, regulation
tissue distribution=> Liver, Beta cells of pancreas
Km=> 10-20 mM (lower in fasting)
regulation=> induced by insulin
What is the last step of glycogenolysis and gluconeogenesis?
G-6-Pase
What are characteristics of G-6-Pase?
- 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
What transporter is used at basal glucose levels?
GLUT 1
What transporter is used when glucose is high? what are the results?
GLUT 2 which results in insulin being released with fuses with plasma membrane at certain levels
