Carbohydrate Metabolism Ch.9 Flashcards
GLUT 2
-low affinity transporter in hepatocytes and pancreatic cells (liver and pancreas)
-captures excess glucose after a meal for storage
-when [glucose] drops below the Km for transporter, much of the remainder bypasses the liver and enters peripheral circulation
Km for GLUT2 is high meaning the liver will pick up glucose in proportion to its concentration in the blood - liver will pick up excess glucose and store it after a meal when glucose is high
-GLUT 2 with glucokinase = glucose sensor for insulin release
GLUT 4
- in adipose tissue and muscle and respond to glucose concentration in peripheral blood
- rate of transport increased by insulin that stimulates movement of more GLUT 4 transporters
- Km close to normal glucose (5mM) meaning that the transporter is saturated when blood glucose levels are a bit higher than normal
- cells with GLUT 4 transporters can increase glucose intake by increasing number of GLUT 4 transporters
How does insulin promote glucose entry into the cell?
GlUT 4 levels are satuarated when glucose levels are only slightly above 5mV, so glucose entry can only be increased by increasing the number of transporters. Insulin promotes the fusion of vesicles containing performedGLUT 4 with the cell membrane
Hexokinase
- Function: Phosphorylates glucose to form glucose 6-phosphate, “trapping” glucose in the cell.
- Regulation: Inhibited by glucose-6-phosphate
- Reversible? irreversible
Glucokinase
- Function: Also Phosphorylates and traps glucose in liver and pancreatic cells, and works with GLUT-2 as part of the glucose sensor in beta cells.
- Regulation: In liver cells, it is induced by insulin
- Reversible? Irreversible
Phosphofructokinase (PFK-1)
- Function: Catalyzes the rate limiting step of glycolysis, phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate using ATP.
- Regulation:Inhibited by ATP, citrate and glucagon. It is activated by AMP, fructose 2,6-bisphosphate and insulin.
- Reversible: Irreversible
Glyceraldehyde-3-phosphate dehydrogenase
- Function: Generate NADH while phosphorylating glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate
- Reversible: Reversible
3-phosphoglycerate kinase
- Function: Performs a substrate-level phosphorylation, transferring a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
- Reversible: Reversible
Pyruvate kinase
- Function: Another substrate-level phosphorylation, transferring a phosphate from phosphoenolpyruvate (PEP) to ADP, forming ATP and pyruvate.
- Regulation:Activated by fructose 1,6- bisphosphate.
- Reversible: irreversible
Why much pyruvate undergo fermentation for glycolysis to continue
Fermentation must occur to regenerate NAD+, which is in limited supply in cells. Fermentation generates NO ATP or energy carriers; it merely regenerates the coenzymes needed for glycolysis
Why is it necessary that fetal hemoglobin does not bind to 2,3-BPG?
The binding og 2,3-BPG decreases hemoglobin’s affinity for oxygen. Fetal hemoglobin must be able to “steal” oxygen from maternal hemoglobin at the placental interference; therefore; it would be disadvantageous to lower its affinity for oxygen.
Fermentation
- lactate dehydrogenase - oxidizes NADH to NAD+ replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate -dehydrogenase (without mitochondria and oxygen, glycolysis would stop when all NAD+ available was reduced to NADH)
- reduces pyruvate to lactate and oxidizes NADH to NAD+ where there is no net loss of carbon because pyruvate and lactate are both 3 carbons
- in yeast cells - conversion of pyruvate (3 carbon) to ethanol (2 carbons) and CO2
- in both the goal is to replenish NAD+
Dihydroxyacetone Phosphate (DHAP)
- used in hepatic and adipose tissue for triacylglycerol synthesis
- formed from fructose 1,6-bisphosphate
- can be isomerized to glycerol 3-phosphate which can be converted to glycerol - backbone of triacylglycerols
1,3 BPG and PEP
high energy intermediates used to generate ATP from substrate level phosphorylation
Irreversible Enzymes in Glycolysis
glucokinase hexokinase PFK-1 pyruvate kinase *how glucose pushes forward the process kinases*
Glycolysis in Erythrocytes - bisphosphoglycerate mutase
- bisphosphoglycerate mutase produces 2,3-BPG from 1,3-BPG in glycolysis
- mutase - moves a functional group from one place to another (phosphate moved from 1 to 2 position)
- 2,3- BPG allosterically binds to β chains of HbA and decreases its affinity for oxygen still allowing 100% saturation in lungs but allows for oxygen unloading in tissues (shifts curve right)
- if too much - may affect saturation
- **2,3-BPG does NOT bind well to HbF so fetus has higher oxygen affinity