Regulating glycolysis Flashcards
Factors controlling flux through metabolic pathways
substrate availability
concentration of enzymes
allosteric regulation of enzymes
covalent modification of enzymes
Relate the factors controlling flux to glycolysis
substrate availability—>glucose
rate limiting enzymes—>hexokinase, phosphofructokinase, pyruvate kinase
enzyme concentration is controlled by hormones (insulin and glucagon)
allosteric regulation of enzymes—>controlled by binding of small molecules to sites other than active site
covalent modification of enzymes—> pyruvate kinase
how is substrate availability (glucose) controlled
uptake of glucose is regulated by GLUT family of transporter proteins
GLUT mechanism
when GLUT is in T1 configuration, it has an open binding site for glucose on the cell exterior
glucose binding causes a conformational change to T2 where the binding site is open to the inside of the cell
glucose is released into the interior of the cell, initiating another conformational change to GLUT, back to T1 so that it can bind to another glucose molecule
GLUT1 location and role
red blood cells
controls basal glucose uptake
GLUT2 location and role
liver cells and pancreatic beta cells
uptake glucose at a rate that is proportional to the amount of glucose present
remove excess glucose from blood
GLUT4 location and role
muscles cells
adipocytes
remove excess glucose from blood
regulated by insulin
role of GLUT2 in substrate availability and hormone release
increase in blood glucose concentration causes GLUT2 to uptake glucose as it has a low affinity for glucose
glucose is metabolised inside the cell to produce ATP, increase in ATP causes ATP-sensitive K+ channels to close and the cell depolarises
Ca2+ channels open and influx of Ca2+ triggers exocytosis of insulin-containing vesicles. insulin released into bloodstream.
role of GLUT4 in substrate availability in muscle cells
GLUT4 is highly responsive to insulin
absence of insulin: GLUT4 stored in intracellular vesicles
rise in insulin: insulin binds to receptors on muscle cells, causing vesicles to move to cell membrane
glucose can enter cells
exercise can also stimulate the translocation
what happens to glucose once it enters the cell
converted to glucose-6-phosphate so it is trapped
catalysed by hexokinase
use of ATP
Mg2+
Makes glucose more polar so it cant easily cross the membrane
Intracellular concentration of glucose remains low– concentration gradient
how enzyme concentration and activity regulates glycolysis
concentrations of rate limiting enzymes are regulated by hormones
insulin upregulates their expression
glucagon inhibits them
how does insulin upregulate enzyme expression
allosteric control definition
inhibition or activation of an enzyme by a small regulatory molecule that interacts at a site other than the active site
allosteric control of hexose kinase
inhibited by glucose-6-phosphate
except for glucokinase in the liver
allosteric control of phosphofructokinase 1
inhibited by ATP and citrate
activated by AMP and fructose 2,6 bisphosphate