Pentose Phosphate Pathway

Question 1

Where does Pentose Phosphate Pathway occur in

Answer 1

Cytosol
Tissues with high levels of HMP pathway enzymes
-tissues active in biosynthesis (lipid)
-liver, adipose tissue, adrenal cortex, testis& lactating mammary gland (30% of oxidation of glucose in the liver occurs via this pathway)
Erythrocytes generate large amt of NADPH for reduction of glutathione
Rapidly proliferating cells need high NADPH

Question 2

Why NADH & NADPH not interconvertible (not metabolically interchangeable)

Answer 2

NADH: generated during catabolism
utilize free energy of metabolite oxidation to synthesize ATP (Oxidative Pn)
-[NAD+]/[NADH]=1000 (Favours metabolic oxidation
NADPH: mainly for anabolism
involved in utilizing free E of metabolite oxidation for otherwise endergonic reductive biosynthesis
-[NADP+]/[NADPH]=0.01 (favours metabolic reduction)

Dehydrogenases in oxidative & reductive metabolism: HIGHLY specific

Question 3

What are pentoses? Why do we need them?

Answer 3

◦ DNA & RNA

◦ Cofactors in enzymes

Question 4

Where do we get pentoses?

Answer 4

Diet and from glucose (and other

sugars) via the Pentose Phosphate Pathway

Question 5

Is the Pentose Phosphate Pathway just about making ribose

sugars from glucose?

Answer 5

(1) Important for biosynthetic pathways
using NADPH, and
(2) a high cytosolic reducing potential from
NADPH is sometimes required to advert oxidative damage by
radicals

Question 6

metabolic significance of HMP shunt?

Answer 6

HEXOSE MONOPHOSPHATE SHUNT. : a metabolic pathway of glucose in which glucose-6-phosphate is oxidized enzymatically twice with NADP as a cofactor to form pentose sugars.

Question 7

OVERALL RXN of PPP

Answer 7

3G6P + 6NADP+ +3H20 6NADPH +6H+ +3CO2 +6F6P +GAP

Question 8

Rapidly proliferating cells need____

Answer 8

1) large qty of NADPH as conversion of ribonucleotides to deoxyribonucleotides requires NADPH as electron source
2) Ribose-5-P (R5P) from HMP pathway

Question 9

Deficiency in HMP Shunt

Answer 9

Glucose-6-P dehydrogenase deficiency
-generally have enough activity for normal function
-sensitive to oxidative damage; particularly erythrocytes
WHY?–> NADPH required to convert oxidized glutathione (GSSG) to reduced glutathione (GSH)

Question 10

What is glutathione?

Answer 10

Glutathione (GSH): thiol tripeptide (glutamate/cysteine/glycine)
-Found in most cells where it is a reducing agent (antioxidant) eg. to keep ptns with essential cysteine grps in reduced state

Question 11

3 stages of PPP

Answer 11

1. Oxidative
   -yield NADPH & ribulose-5-P (Ru5P)
   3G6P+ 6NADP+ +3H20–> 6NADPH +6H+ +3CO2 +3Ru5P
2. Isomerization& Epimerization
   -3Ru5PR5P + 2Xu5P
   freely reversible
3. series of C-C bond cleavage and formation rxns
   2Xu5P +R5P 2F6P +GAP
   freely reversible

Question 12

Major function of GSH in RBC

Answer 12

1. Eliminate H202 & other reactive oxygen metabolites (organic hydroperoxides) that can damage cellular ptns & lipids
2. Enzyme: glutathione peroxidase & GSH is then oxidized to GS-SG
3. H202 (or ROOH) +2GSH–>GS-SG +H20

Question 13

What catalyses regeneration of reduced glutathione (GSH) with GSSG being reduced by NADPH

Answer 13

Glutathione reductase

GSSG +NADPH +H+–> 2GSH +NADP+