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29 Cards in this Set
- Front
- Back
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Describe the following glucose transporters:
GLUT1 GLUT2 GLUT3 GLUT4 GLUT5 |
GLUT1= most cells, continual glucose uptake, Km=1mM
GLUT2=in LV and pancreatic B cells, transports HIGH glucose conc. and B cells secrete insulin. Km>15mM GLUT3=like GLUT1 Km=1mM GLUT4=insulin-dependent and levels increase with physical activity Km=5mM GLUT5=in small intestine and transports fructose |
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What is the purpose of hexokinase phosphorylating glucose?
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Hexokinase phosphorylates glucose to be glucose-6-phosphate so that the charged group traps the molecule inside of the cell and so it is de-stabilized to get it ready for the rxn
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Why is glucose-6-phosphate isomerize and what enzyme does that? How is this done?
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glucose-6-phophate is isomerized to fructose-6-phosphate by phosphoglucose isomerase to move the keto group next to C3 so its in the right position for cleavage between C3 and C4. The aldo ring opens, moves the OH then the ring forms again
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What is unique about the reaction from glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate?
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It is the only redox reaction. First GAP is oxidized with NAD+ and water This step is held at an intermediate of a thioester to make the reaction favorable and then it is dehydrated and a phosphate group is added
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What enzyme used in glycolysis has a Histadine involved in the reaction?
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Phosphoglycerate mutase has a histine and phosphorylates 3-phosphoglycerate at C-2 then removes the phosphate at C-2 to make 2-phosphoglycerate
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What is the Net reaction of glycolysis?
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Glucose + 2 Pi + 2ADP + 2NAD+ -----> 2 pyruvate + 2 ATP + 2NADH+ + 2H+ + 2Water
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Glucose 6-phosphate is a key intermediate to what pathways?
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pentose phosphate pathway
glycogen synthesis Triglyceride (glucose 6-P -->glycerol +Acetyl CoA) |
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Pyruvate is a key intermediate to what pathways?
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TCA
Alanine synthesis |
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1,3 bisphophoglycerate and 3 phosphoglycerate are intermediates to what important synthesis?
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hemoglobin
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What AA does 3 phosphoglycerate synthesize?
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serine
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What is the rapoport-lueberling shunt?
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When RBC take priority over making ATP, instead of 1,3 bisphospoglycerate making ATP and going to 3-phosphate, it is converted to 2,3 bisphosphoglycerate by 1,3 BPG mutase.
This bipasses enzyme phosphoglycerate kinase |
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What is the only redox reaction in glycolysis and why can this reaction cause problems?
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1,3 Bisphophoglycerate is synthesized by adding a Pi from NAD+ with the help of enzyme glyceraldehyde 3-phosphate dehydrogenase. This uses up all of the NAD+ and causes an imbalance. To solve this problem, under anaerobic conditions lactate dehydrogenase converts NADH to lactate which produces NAD+. Under aerobic conditions NADH is converted to NAD+ from oxidation of Acetyl Co. Microorganisms convert acetaldehyde to ethanol which makes NAD+
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What tissues especially depends on anaerobic glycolysis?
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RBC
skeletal muscles medulla of kidneys eyes tumors |
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What is the difference between global and local metabolism control?
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global= regulates many different reaction when regulating energy states
local=regulating individual reactions like substrates and products |
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What are the 3 irreversible reactions in glycolysis?
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Rxn1: glucose--->glucose 6-phosphates (hexokinase)
Rxn3: fructose-6-phophate---> 1,6 bisphosphate (phosphofructokinase) Rxn10: phosphoenolpyruvate--->pyruvate (pyruvate kinase) |
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What enzyme is the master regulator in glycolysis and why is that so?
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phosphofructokinase is the master regulatory because fructose 1,6 bisphosphate has no choice but to commit to glycolysis while prior product glucose 6-phosphate can either synthesize glycogen or enter the pentose phosphate pathways
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How does hexokinase inhibit glycolysis and shunts glucose to cells that need it?
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inactive PFK--> increase fructose 6-phosphate--> increase glucose-6 phosphate---> decrease hexokinase
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What specialized isozyme of hexokinase does the liver contain and what is it for?
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glucokinase: it is induced by insulin and has a very low affinity for glucose so it only phosphorylates it when there is alot of glucose (prevents LV from using glucose before letting other tissues use glucose first)
It is not inhibited by glucose 6 phosphate so glycolysis always occurs when energy charge is high |
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Describe the structure of phosphofructokinase.
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6 binding sites:
F6P (substrate) ATP (substrate) ATP (inhibitor) AMP (activator) citrate (inhibitor) F-2,6-BP (activator) H+ (inhibitor) |
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What products inhibit PFK?
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ATP
lactate/H+ citrate |
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What product activate PFK?
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AMP
F 2,6-BF |
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Why does ATP inhibit PFK? What kind of control does this represent?
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ATP is an allosteric inhibitor that lowers the affinity for F6P. This is global control
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How does fructose 2,6 bisphosphate an allosteric activator of PFK? How is the enzyme that synthesizes this product regulated?
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Fructose 2,6 bisphosphate: it increases affinity for F6P, lowers the inhibiting effect of ATP, its a separate binding site
made by phosphofructose kinase 2 (both kinase and phosphatase domain). PFK2 is also stimulated by insulin When glucagon is present (low glucose) PKA is activated by the receptor which phosphorylates PFK2. This inactivates the kinase portion and activates the bisphosphotase making levels of F 2,6 BP go down thus inactivating PFK |
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what are the fates of pyruvate?
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TCA: Acetyl CoA or oxaloacetate
Lactate Alanine |
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What happens to pyruvate kinase when there are high levels of glucose? when there are low levels of glucose?
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Hi: Pyruvate kinase is dephosphorylated and allows for phsophoenolypyruvate to be converted to Pyruvate
Lo: pyruvate kinase is phosphorylated which makes the enzyme less active |
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Too much ATP inhibits what 2 enzymes in glycolysis?
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Phosphofructokinase
pyruvate kinase |
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Lactate is a product of pyruvate. What enzyme does lactate inhibit in glycolysis? Why is this important?
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phosphofructokinase is inhibited. This guards against metabolic acidosis
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What is haemolytic anaemia? Spherocytosis? Thalassameia, non-spherocytic hemolytic anemia?
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Haemolytic anaemia is the destruction of RBC
Spherocytosis=defects in RBC membrane Thalassemia=defects in cell non-spherocytic hemolytic anemia=abnormal glycolytic enzymes |
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What is the Warburg effect?
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When tumors have increased glucose uptake and increased glycolysis which produces higher levels of lactate. They rely on glycolysis because they are hypoxic because they turn off the mitochondria to inhibit apoptosis. Hypoxia activates hypoxia inducible transcription factor which enhances glycolytic enzymes and pbl vessel growth
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