Pentose phosphate pathway

Question 1

Byproduct of the PPP ?

Answer 1

NADPH

As opposed to glycolysis, which yields NADH, the PPP yields NADPH.

This NADPH does not give energy equivalents.

Question 2

PPP takes place in ?

Answer 2

Cytosol

Question 3

Committed step of PPP & rate limiting step :

Answer 3

Glucose-6-phosphate —> 6-phosphogluconate

via Glucose-6-phosphate dehydrogenase (G6PD)
Releases NADPH

This step is oxidative and irriversible

Question 4

PPP oxidative pathway makes

Answer 4

NADPH

Question 5

The PPP and glycolysis are linked by what enzymes rearranging carbons ?

Answer 5

Transketolase
Transaldolase

Question 6

Fate of ribose

Answer 6

Excess ribose in the diet can enter glycolysis via PPP.

Question 7

Transketolase prosthetic group:

Answer 7

Thiamine pyrophosphate

Question 8

Syndrome that present as a triad of ophthalmoplegia, ataxia and confusion due to chronic thiamine deficiency in context of chronic alcoholism.

Alcohol inhibit absorption of thiamine.

Answer 8

Wernicke’s encephalopathy

Question 9

Thiamine is used as a cofactor in many reactions, but only one uses it as its only cofactor making it useful to dx a thiamine deficiency :

Answer 9

Transketolase enzyme (enzyme of the PPP)

Non oxidative rx

Pyruvate dehydrogenase and a-ketoglutarate dehydrogenase also uses it as cofactor but have other coenzymes also.

Question 10

Thiamine deficiency results in decreased glucose utilization, which is especially pronounced in the :

Answer 10

CNS (brain).

Question 11

Side effect of thamine deficiency if glucose introduced :

Answer 11

Lactic acidosis

Why you need to give thiamine before reintroducing glucose in a malnourished or alcoholic pt.

Question 12

An increase in erythrocyte transketolase levels after thiamine infusion is diagnosic of :

Answer 12

thiamine deficiency

Question 13

Main regulator of PPP

Answer 13

NADP+

Question 14

A rapidly dividing cell requires more:

Answer 14

ribose-5-phosphate

NOT NADPH (Skips the first part of the rx)

Question 15

Oxidative pathway

Answer 15

Glycolysis —> PPP

glucose-6-phosphate –> 6-phosphogluconate via G6PD

Question 16

Non-oxidative pathway

Answer 16

PPP<—-> Glycolysis

Transketolase

Question 17

Glutathione is a tripeptide made of :

Answer 17

Glutamate
Cysteine
Glycine

Question 18

Role of glutathione

Answer 18

Helps relieve the oxidative stress build up in RBCs

G6PDH required for maintaining glutathione in the reduced state and do its job!

Question 19

What pathway is important to reduce oxidative stress ?

Answer 19

PPP

Question 20

G6PD deficiency pathophysio

X linked

Answer 20

Hemolytic Anemia & jaundice
No more NADPH being produced, H2O2 accumulates, lysis of RBCs (breakdown of RBC - bilirubin)

May be partial - for instance it may function at 50% which may be sufficient for day to day oxidative stress management and thus people will have sx only when there is excessive build up ROS.

Question 21

How does NADPH helps maintain the oxidative- reductive reactions?

Answer 21

NADPH form from PPP used to maintain the reduced pool of glutathione.

Reduced pool of glutathione is required to prevent lysis of RBCs.

Question 22

What are Heinz bodies ?

Answer 22

oxidized Hb conglomerates (denatured Hb precipitates) in RBCs removed by splenic macrophages, leaving behind characteristic bite cells.

Question 23

Oxidative stressors :

Avoid if confirmed or suspected G6PD def.

Precipiatate hemolytic anemia & jaundice !

Answer 23

Antimalarial drugs
Atb such as sulfa & chloramphenicol
Fava beans also!

Pt presenting with jaundice after introduction of a medication may be an indicator that he/she has G6PD deficiency.

Question 24

Glutathione reductase and glutathione peroxidase deficiencies may present as :

Answer 24

G6PD deficiency

Question 25

Why is G6PD deficiency most severe in erythrocytes?

Answer 25

The only way of generating NADPH is via G6PD in the the RBCs wheras other cells have other enzymes which can generate NADPH.

Question 26

G6PD deficiency is associated with protection against what disease ?

Answer 26

Malaria

Question 27

Cytochrome P450 is an enzyme that works on xenobiotics by doing what ?

Answer 27

Adds OH groups to lipophilic substances that enter our body making them more water soluble in order to be more efficiently excreted. | This enzyme uses NADPH as a cofactor!

Question 28

NADPH oxidase is required in what cell to perform oxidative burst ?

Answer 28

Neutro ## Footnote In case of G6PD deficiency, lack of NADPH would interferes with proper oxidative burst by neutrophils therefore î risk of infections.

Question 29

Chronic granulotamous disease (CGD) results from :

Answer 29

NAPDH oxidase deficiency ## Footnote When the enzyme itself is deficient NOT like lack of NADPH required as a cofactor for NAPDH oxidase. This means that the person will have no defence against **all opportunistic infections**.