Glycolysis and PPP

Question 1

describe the GLUT transporters

Answer 1

• GLUT 2 = liver
• GLUT 1 and 3 = neurons and brain
• GLUT 1 = erythrocytes
• GLUT 4 = adipose tissue and muscle in response to insulin
  
  • increases in presence of insulin

Question 2

describe the formation of glucose 6 phosphate

Answer 2

• glucokinase in liver has high Km (more active when the blood glucose is elevated; functions as a glucose sensor)
  
  • also present in B-cells of pancreas (MODY-2 = rare inherited form of DM since the B-cells of pancreas cannot respond to high blood glucose levels)
• other tissues contain hexokinase which has a low Km for glucose

Question 3

describe the major points of PPP

Answer 3

• all enzymes are in the cytosol
  
  • glucose 6 phosphate dehydrogenase (key enzyme)
• pentose phosphate pathway forms NADPH
• PPP forms ribose phosphate which is used for purine and pyrimidine nucleotide synthesis
• transketolase requires thiamine pyrophosphate (TPP aka vit. B1)

Question 4

describe the energy investment phase of glycolysis

Answer 4

• 2 phosphorylation rxns that requires 2 ATP
• PFK-1 is the 2nd irreversible rxn of glycolysis and also the most important regulated step (allosteric regulated enzyme)

Question 5

describe the cleavage of 6C sugar into 3C intermediates (stage 2)

Answer 5

• aldolase A is present in muscle and aldolase B is in liver
• the isomerase converst the dihydroxyacetone phosphate to glyceraldehyde 3-phosphate to enable it to be further metabolized by glycolysis
• glucose is cleaved to 2 molecules of glyceraldehyde 3-phosphate

Question 6

describe the energy generation phase of glycolysis (stage 3)

Answer 6

• glyceraldehyde 3-phosphate dehydrogenase results in the formation of an NADH
• phosphoglycerate kinase results in the formation of the first ATP (substrate level phosphorylation, SLP)
• 1,3-BPG is a high energy intermediate that results in the formation of ATP without involving the mitochondrial ETC
  
  • SLP important during hypoxia

Question 7

describe the second part of the energy generation phase (2-phosphoglycerate to pyruvate)

Answer 7

• phosphoenolpyruvate is a high energy compound that results in the formation of ATP without the involvement of the ETC in mt (substrate level phosphorylation)
  
  • SLP important during hypoxia and in RBC
• pyruvate kinase is an irreversible rxn

Question 9

describe the Cori cycle

Answer 9

Question 10

describe the anaerobic fate of pyruvate

Answer 10

• pyruvate formed in glycolysis is metabolized anaerobically in the absence of mt or poorly vascularized tissues
• the NADH formed by the glyceraldehyde 3-P dehydrogenase rxn is reoxidized to form NAD+; this allows glycolysis to proceed even in the absence of mt
• LDH is a cytosolic enzyme
• the direction of the rxn depends on the NADH/NAD+ ratio
  
  • higher the NADH levels, the rxn is driven towards lactate formation

Question 12

name the 3 irreversible rxns (regulatory steps) in glycolysis

Answer 12

• glucokinase/hexokinase
• phosphofructokinase-1
• pyruvate kinase

Question 13

name the 2 SLP rxns in glycolysis

Answer 13

• phosphoglycerate kinase (reversible)
• pyruvate kinase (irreversible)

Question 14

name inhibitors of glycolysis

Answer 14

• pentavalent arsenate poisoning results in inhibition of glyceraldehyde 3-P dehydrogenase enzyme
• in clinical labs, blood is collected in fluoride containing tubes for the estimation of blood glucose
  
  • if fluoride is not added, there would be reduction in the glucose due to its utilization by RBC and WBC, which leads to erroneously low blood glucose
  • fluoride inhibits enolase