metabolismo de la glucose part 2 Flashcards
diffusion Vs. facilitated diffusion Vs. coupled active transport
GLUT Vs. SGLT ?
GLUT> allow glucose to go across the membrane, down a concentration gradient and they function IN REVERSE; they allow glucose to enter the cell or to leave the cell
SGLT> these transporters take glucose from a domain that has high sodium and drives it to where there’s low sodium. they bring in two sodiums for each glucose. main places where these transporters are used are in the gut (glucose absorption) and the kidneys to retrieve any glucose that has spilled into the urine
regulation of enzyme activity Vs. regulation of gene transcription.
regulation of enzyme activity is ‘acute’ and much faster than regulation of hormone activity, which is much slower, and more ‘adaptive’
how does enzyme regulation occur under insulin/glucagon ?
signal transduction/ kinase cascades
insulin Vs. glucagon mode of action
insulin signals through tyrosine kinases “kinase cascade” - doesn’t involve cyclic AMP
while counter-regulatory hormones (that counter the activity of insulin) e.g.epinepherine) they signal through G-protein coupled receptos and elevations in cyclic AMP
GPCR
Activate enzymes, control transcription, stimulate secretion
glucose metabolism generic cell
liver: fed-fasted transition
overall glycolysis rxn
glycolysis first 2 irreversible steps
glycolysis last 2 irreversible steps
Position of ATP on the bioenergetic scale of phosphate compounds
where are SGLT’s found ?
SGLT’s found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron; where they contribute to renal absorption of glucose
the GLUTs ?
facilitative GLUT transporters allow glucose to go down a concentration gradient
most glucose enters cells through the GLUT transporters
glucose becomes trapped or committed to glycolysis once its phosphorylated into glucose 6-phosphate inside the cell; since these transporters wont transport glucose 6-phosphate —> concentration gradient of high glucose out and low glucose inside is maintained: very little free glucose inside the cell.
5 most important GLUT types ?
why is Km important ?
the four known hexokinases ?
GLUT-2, GLUT-4, HK-2, HK-4
who are the good guys ?
GLUT-2 and HK-4 –> both function in the liver and beta cells and both have a high Km and low affinity; makes them sensitive to changes in blood glucose
HK’s 1,2, and 3 Vs. HK-4
HK 1,2,3 –> are inhibited by G-6-P while Pi releases the inhibition and all of them have a high affinity to G-6-P
HK-1 has a house keeping activity (energy production): a catabolic activity
HK-2 in muscle and adipose has an anabolic function; G-6-P it produces goes into glycogen synthesis in both.
Hexokinases I,II,III are saturated at normal blood glucose concentration (5mM), whereas Hexokinase IV is not.
• The amount of glucose6-P formed by HK-IV is sensitive to a rise in blood glucose.
Glucokinase is not inhibited by glucose6-P.
HK-4 affinity Vs. other HK’s ?
what exactly is the main gauge of the amount of glucose in the blood ?
The amount of glucose6-P formed by HKIV is sensitive to a rise in blood glucose.
glucose-insulin correlation graph
explain the orderly process of hormone-independent, glucose-dependent insulin secretion into the blood
glucose gets into the cytosol via GLUT 2 of the beta cells (GLUT-1 in humans) where HK-IV converts it to G-6-P –> high G-6-P is an indicator of high blood glycose –> glycolysis –> high ATP
beta cells make insulin and they transport it from the TGN (Trans Golgi Network) to special vesicles in which insulin gets stored #it will be independent from the transport of other proteins from the TGN (a very specialized system). these insulin storage vesicles are pre-docked at the plasma membrane.
what translates into an increase in ATP levels that close the ATP-dependent K+ channel ?
the low affinity of HK-IV makes it more saturated as glucose levels go up –> more G-6-P would be generated , which would enter glycolysis –> more ATP –> K+ channel closes
jsnxmnbdsbndjdentire glucose-depdendent insulin release diagram
how do we know that HK-IV is the glucose sensor in the blood ?
there’s a genetic form of diabetes called MODY 2 and the molecular defect is known and its a change in glucokinase’s affinity for glucose and changing the affinity of glucokinase to glucose changes the set point so now the beta cells do not respond as glucose gets above 5 mM but only start responding when glucose gets above 7 mM. individuals with MODY 2 just have a different set point (of when the beta cells respond) and everything else works fine.
