Biochemistry-Pentose Phosphate Pathway Flashcards
What is the primary spot of regulation in the pentose pathway? What molecules turn it on and off?
Glucose-6-P Dehydrogenase (G6PD). NADPH is a potent inhibitor. Insulin upregulates G6PD gene expression.
What are the irreversible steps in the pentose pathway?
Steps 1-3. Gluc-6-P is oxidized to form 6-phosphogluconolactone and NADPH by G6DH. 6-phosphogluconolactone is hydrolyzed to 6-phosphogluconate by 6-phosphogluconolactone hydrolase. 6-phosphogluconate undergoes oxidative decarboxylation by 6-phosphogluconate dehydrogenase to form another NADPH, a CO2 and ribulose-5-P.
What tissues rely heavily upon the irreversible, reductive steps of the pentose phosphate pathway?
Tissues that are undergoing NADPH-dependent biosynthesis of fatty acids (adipose tissue) and steroid hormones (reproductive organs). Erythrocytes also require NADPH to keep glutathione reduced.
What tissues rely upon the reversible steps of the pentose phosphate pathway?
All cells that are actively synthesizing nucleotides and nucleic acids.
What are the reversible steps of the pentose pathway?
If the cell has a higher demand for NADPH for biosynthetic reactions, the pathway will move towards the production of glycolysis intermediates. If the cell has a high demand for nucleic acid building blocks, the pathway will move towards the production of ribose-5-P.
How is sedoheptulose-7-P made in the pentose phosphate pathway?
Transketolase can take C1 and C2 from xylulose-5-P and add them to ribose-5-P to form sedoheptulose-7-P. Transaldolase can also take C1-C3 from fructose-6-P and add them to erythrose-4-P to form sedoheptulose-7-P.
How are the glycolysis intermediates made in the pentose phosphate pathway?
Transaldolase can take C1-C3 of sedoheptulose-7-P and add them to glyceraldehye-3-P to form fructose-6-P. Transketolase can also take C1 & C2 from xylulose-5-P and add them to erythrose-4-P to form fructose-6-P and glyceraldehyde-3-P. Also, glyceraldehyde-3-P is a byproduct of the transketolase reaction with xylulose-5-P to form sedoheptulose-7-P.
What enzyme would probably be active right after the irreversible steps of the pentose phosphate pathway if you were in a cell that really needed nucleic acids for DNA synthesis?
Ribose-5-P isomerase. It takes ribulose-5-P straight to ribose-5-P which is used in nucleic acid synthesis.
What is the key difference between NADH and NADPH in hepatocytes?
The ratio of NAD/NADH is about 1000 where the ratio for NADP/NADPH is about .1. Thus, NAD+ is heavily used for oxidation and NADPH is heavily used for reduction.
Glutathione is a key protector in our body agains hydroxyl radical damage. How is glutathione preserved so it can continue doing its job?
Glutathione reductase reduces glutathione with NADPH after it was oxidized by glutathione peroxidase.
How does NADPH play a role in secretion of toxic metabolites?
It reduces O2 in Cyt P450 two times to make the superoxide anion. This anion can insert itself into hydrocarbons, making them more soluble and easier to excrete.
What enzyme is likely mutated in a child with chronic granulomatous disease?
NADPH oxidase. This enzyme uses NADPH to pass electrons to a heme group which gives them to oxygen and produces ROS used for cell defense.
What role does NADPH play in vascular tone?
It is necessary for the reduction of O2 so it can react with L-Arg in order to form NO.
A patient comes to see you after taking antibiotics for an infection that he had. He complains that he gets tired very easily. You notice his skin is pale and the whites of his eyes are slightly blue. What has likely caused his exhaustion?
He could be deficient in Glucose-6-P Dehydrogenase. This severely affects the RBCs because they rely solely upon NADPH for reduction of glutathione so glutathione can protect them from ROS. In an inflammatory condition, ROS increase and can caused hemolytic anemia in people with this enzyme deficiency.
What pentose phosphate pathway enzyme is affected in thiamine deficiency?
Transketolase. It requires TPP.
Which pentose phosphate pathway enzyme does not need a cofactor because it forms a schiff base in the enzyme active site?
Transaldolase.
What are the net products from the pentose phosphate pathway?
2 NADPH, CO2 and Ribulose-5-P
What does this indicate?
Heinz bodies. These form from cross-linking of disulfide bonds in Hb proteins in people with G6PDH deficiency
