Lecture 7: Glycolysis: Regulation Flashcards
(55 cards)
Glucokinase overview
glucose sensor
affects insulin secretion from pancreatic beta cells
phosphofructokinase 1 (PFK-1)
one of 3 metabolic valves in glycolytic pathway
allosterically regulated
disarcharide sugars
maltose, sucrose, lactose
give rise to monosacchardes sugars to enter glycoltic pathway
Regulated valves
rate-limiting enzymes in metabolic pathways
open and close in response to cell conditions
Regulation of glycolytic pathway (glycolysis and gluconeogenesis)
reversible steps in both regulate in both pathways (shown wide in pictures)
irreversible steps have actual changes in free energies (delta G) that are very negatie and require PATHWAY SPECIFIC ENZYMES (shown as skinny)
glucokinase and hexokinase
catalyze same reaction
differ in properties
Hexokinase I
high affinity for substrate (at low concs, enzyme has half activity)
phosphorylates a variety of hexose sugars
in ALL tissues
INHIBITED by product of reaction (glucose-6-P)
Glucokinase
low affinity for substrate (it takes a lot more substrate to reach half max enzyme activity)
Spefic for GLUCOSE
only in liver and pancreatic cells
NOT inhibited by glucose-6-P
Role of glucokinase in liver cells
high blood glucose levels-> hexokinase and glucokinase active in liver cells
hexokinase will become inhibited
traps glucose in liver cells more than in other tissues because glucokinase doesn’t become inhibited, which allows more glucose to be trapped as gluco-6-P
liver is where we store most glycogen
role of glucokinase in pancreatic beta cells
glucokinase sequesters glucose inside cells
initiate signaling pathway leading to release of INSULIN into blood
this makes glucokinase a glucose sensor
Km values
tells what substrate concentration is needed to reach half maximum activity
Glucose transporters are called
GLUC transporters
review slide 7
review slide 7
what happens to flux through glycolytic pathways when glucokinase is activated by glucose?
flux will increase because glucokinase is activated at high glucose levels (while hexokinase is inactivated)
what turns off glucokinase?
a lack of glucose
what effect would a mutation in glucokinase have on insulin secretion
insulin secretion will decrease, but won’t go away because hexokinase can still get some to be secreted
How would you treat diabetes that is cauased by glucokinse mutation
give insulin
diabetes not actually caused by this!
See slide 9 for questions
see slide 9 for questions
is PFK1 stimulated or inhibited by a high energy charge (keep in mind that this is in the ATP using stage)
INHIBITED
if we have a lot of ATP around, we don’t need to make more ATP.
we do need enough ATP around to make the reaction happen, but we need to have a need to make ATP
T state
INACTIVE conformation
R state
ACTIVE conformation
Allosteric regulator of PFK-1
a tetramer
F-2,6-BP–> super activator of PFK-1 activity
AMP——–>activator
ADP——–> activaor
Citrate—-> inhibitor
ATP——–> inhibitor
citrate and PFK-1 activity
inhibits
because citrate is a metabolite of the citrate cycle, it builds up when energy levels are high
F-2,6,BP and PFK-1 activity
super-duper activator (activating PFK-1 is its only job)
NOT a metabolite of glycolysis, just a regulatory molecule
