Glucose regulation

Epinephrine functions

use stores of ATP and phosphocreatine (phosphate store in muscles for making ATP)

use up stores of glycogen and oxygen

start gluconeogenesis in liver

GLUT1

Glucose uptake in Brain, kidney, colon, placenta erythrocytes

GLUT2

Rapid uptake or release of glucose in Liver, pancreatic B cells, small intestine, kidney

GLUT3

Glucose uptake in brain, kidney, placenta

GLUT4

Insulin-stimulated glucose uptake in Heart and skeletal muscle, adipose tissue

Regulation of GLUT4 by insulin signaling Step 1

When insulin binds to receptor the activated receptor phosphorylates IRS-1 protein which recruits GRB2 and Ras pathway activated

Regulation of GLUT4 by insulin signaling Step 2

IRS-1 activates PI3 kinase which catalyzes the addition of a phosphate group to the membrane lipid PIP2 to make PIP3

Regulation of GLUT4 by insulin signaling Step 3

PIP3 binds a protein kinase called Akt which is activated by other protein kinases

Regulation of GLUT4 by insulin signaling Step 4

Akt catalyzes phosphorylation of key proteins leading to increase in glycogen synthase and recruitment of GLUT4 to the membrane

Insulin moving GLUT4 into plasma membrane step 1

Glucose transporters stored within cell in membrane vesicles

Insulin moving GLUT4 into plasma membrane step 2

When insulin binds to receptor, transporter filled vesicles move to surface and fuse w/ plasma membrane

Insulin moving GLUT4 into plasma membrane step 3

When insulin drops glucose transporters are removed by the plasma membrane by endocytosis, forming small vesicles

Insulin moving GLUT4 into plasma membrane step 4

The smaller vesicles fuse w/ larger endosome

Insulin moving GLUT4 into plasma membrane step 5

Patches of the endosome enriched w/ glucose transporters bud off to become small vesicles, ready to return to the surface when insulin levels rise again

GLUT 5

Adsorption of fructose in Small intestine

SGLT1

Na glucose synport

secondary active transporter using Na gradient to recover glucose in intestinal and kidney cells

step 1 in glycolysis and gluconeogenesis regulated by

Glucose-6-Phosphate

Glycolysis reciprocal regulation by energy charge

High ATP inhibits glycolysis

High AMP activates glycolysis

Glucagon inhibits glycolysis

Insulin activates glycolysis

Gluconeogenesis reciprocal regulation by energy charge

High AMP inhibits gluconeogenesis because you need energy to make glucose

High ATP activates gluconeogenesis

Glucagon activates gluconeogenesis

Insulin inhibits gluconeogenesis

Cori cycle

lactic acid recycling during anaerobic glycolysis in the muscles

most regulated/committed step in glycolysis and gluconeogenesis

Step 3

What does PFK-1 do

Catalyzes most committed step of glycolysis (step 3)

Synthesizes fructose 1,6-biphosphate from Fructose-6-Phosphate

fructose 2,6 bisphosphate regulation of glycolysis and gluconeogenesis

suppresses gluconeogenesis by inhibiting fructose 1,6 bisphosphatase

induces the glycolysis pathway by activating PFK-1

ATP sigmoidal kinetics

ATP is both substrate and inhibitor of phosphofructokinase-1

How does insulin activate glycolysis?

by dephosphorylating PFK-2 (turns on) and Fructose 2,6 bisphosphatase-2 (turns off)

How does glucagon activate gluconeogenesis?

by phosphorylating PFK-2 (turns off) and Fructose 2,6 bisphosphatase-2 (turns on)

What does PFK2 do?

Activates glycolysis

Synthesizes fructose-2,6-bisphosphate from Fructose-6-Phosphate

Bifunctional enzyme

Phosphofructokinase-2 and fructose 2,6-bisphosphatase activities are found on the same enzyme

Unphosphorylated increases PFK2 so more F26BP and glycolysis

Phosphorylated increases fructose 2,6-bisphosphatase so less F26BP and less glycolysis

Regulation of pyruvate carboxylase

Acetyl-CoA increases fat breakdown and gluconeogenesis

After eating

Insulin release from pancreas

Glucose high in blood, uptake into cells

Glycolysis starts

Gluconeogenesis stops

Glycogen synthesis begins

Fasting

Glucagon release from pancreas

Glucose low in blood, uptake low in cells

Glycolysis stops

Gluconeogenesis starts

Glycogen breakdown starts