Week 3 Flashcards
What is the primary role of red blood cells?
transporting oxygen
What is the only source of energy for red blood cells?
Glycolysis, therefore lactate is produced. The intermediates of glycolysis can be redirected to other processes to ensure that lactate levels remain low in circulation
10-20% of the glycolysis intermediate 1,3 biphosphoglycerate is diverted to?
2, 3 biphosphoglycerate, tells RBC to give up O2 to tissues
10% of the glycolysis in RBC is shunted into the PPP, to provide what?
protection against oxidative stress
What does PPP provide in normal nucleated cells?
NADPH for biosynthetic, anabolic reactions.
What is the double activity of 2, 3 BPG?
mutase and phosphatase
At what point doe the PPP branch from glycolysis?
glucose 6 phosphate
If the pentoses needed from PPP are not needed they are shunted back to glycolysis through ?
fructose 6P and glyceraldehyde 3P
What is the electron acceptor in the PPP?
NADP+
What damage can the PPP protect against?
The damaging effects of oxygen free radicals - cells of the eye and erythrocytes
What are the 2 stages of the pentose phosphate pathway?
irreversible redox stage and a reversible interconnection stage
What happens in the first, irreversible stage of PPP?
NADPH is yielded and pentose phosphate
What happens in the second stage, the reversible interconnection stage?
To reconvert pentoses to metabolic intermediates of glycolysis.
Why is the PPP important for RBCs?
As they do not need to generate pentoses for nucleic acid synthesis but need to make NADPH and energy .
Is ATP consumed or made in the PPP?
no ATP is consumed or made.
What are the 2 purposes of PPP?
Provides ribose 5 phosphate for nucleotide synthesis
Provides biochemical reductants - NADPH
What are the 3 redox enzymes for generating NADPH?
G6P dehydrogenase
Lactonase
6 phosphogluconate dehydrogenase
In the redox reactions for PPP what needs to be kept at 1%?
NADPH needs to be kept at a very low level as it is a driver for glycolysis, TCA and OXPHOS
What are the key enyzymes in the interconnection phase of PPP?
isomerases and epimerases
Transketolase (catalyzes 2C unit transfers)
Transaldolase (catalyzes 3C unit transfers to sugars)
How is ribulose 5 phosphate in PPP converted to fructose 2 phosphate and glyceraldehyde 3 phosphate?
2 or 3C transfers
In the RBC the glycolytic intermediates of the PPP continue through glycolysis to lactate, what is the result of this?
Glucose being only temporarily shunted away from mainstream glycolysis
What is the rate limiting step of PPP?
Glucose 6 phosphate dehydrogenase
What inhibits the rate limiting step of PPP?
NADH inhibits the rate limiting step of PPP: G6P dehydrogenase
What increases the flux of the PPP Cycle?
An increased demand for NADPH increases the flux of the cycle by relieving inhibition of G6PD enzyme
What increases G6PD activity and the absorption of glucose?
Insulin
What is not used in ATP synthesis?
Electrons
What is used in biomolecule synthesis?
Electrons
What are some other uses of NADPH?
- reducing ROS reactive oxygen species/chemicals
- hydroxylation of steroid intermediates by CYP450
- Detox of Zenobiotics - hydroxylation - Microsomal CYPs
- Phagocytosis - pathogen destruction
- Synthesis of nitric oxide
What protects cells from highly reactive oxygen derivatives?
NADPH and Glutathione
What is seen in a blood film of a patient suffering from glucose 6 phosphate dehydrogenase deficiency?
Heinz bodies
Where does gluconeogenesis get its sources of glucose from?
- Glucose from 3C compounds - glycerol, lactate, pyruvate
- Lipids
- Glucose from amino acid metabolism intermediates
