Pentose Phosphate Pathway

Question 1

Purpose of the pentose phosphate pathway

Answer 1

Alternate route for oxidation of glucose (other than glycolysis); does not give you energy, gives you NADPH in order to provide cell with ribose-5-phosphate

Question 2

1. Location of PPP (HMP shunt)
2. Substrate?
3. Two stages of PPP

Answer 2

1. Cytosol
2. Glucose-6-phosphate
3. Oxidative/irreversible (first 3 steps); nonoxidative/reversible (rest of steps)

Question 3

Results of the oxidative/irreversible stage

Answer 3

2 molecules of NADPH per molecule of glucose-6-phosphate (NADPH is not generated in nonoxidative stages) and synthesis of ribulose-5-phosphate and production of CO2

Question 4

1. First step of PPP

2. Does this happen in fasting or well fed state? Why?

Answer 4

1. Glucose-6-phosphate to 6-phosphogluconolactone by glucose-6-phosphate dehydrogenase
2. Well fed; if you were fasting, you would not have any glucose-6-phosphate so reaction could not occur

Question 5

What inhibits this pathway?

Activates it?

Answer 5

Inhibited by high NADPH

Activated by high Insulin

Question 6

What is mainly happening in the non-oxidative stages?

Answer 6

Series of sugar interconversion reactions — ribulose-5-phosphate to ribose-5-phosphate

Question 7

Two main takeaways from nonoxidative stage

Answer 7

1. Ribose-5-phosphate transfers 2 carbons via transketolase to get glyceraldehyde-3-phosphate
2. Sedaheptulose-7-phosphate transfers 3 carbons via transaldolase to get erythrose-4-phosphate

Question 8

1. What does transketolase require in order to function normally

~2. Name 3 other enzymes that also require this for proper functioning

Answer 8

1. TPP

2. PDH, alpha ketoglutarate dehydrogenase and branching amino acid dehydrogenase

Question 9

What is used clinically to assess Thiamine levels to see if there is a deficiency ?

Answer 9

Erythrocyte transketolase activity (ETKA)

Question 10

Overview: role of NADPH in:

1. Liver
2. Adrenal cortex
3. Erythrocytes
4. WBC

Answer 10

• Reductive biosynthesis means NADPH is going to provide hydrogen
  1. Cholesterol and fatty acid synthesis / reductive biosynthesis
  2. Steroid hormone synthesis / reductive biosynthesis
  3. Maintains glutathione in reduced state / protection against H2O2 (reactive oxygen species)
  4. NADPH oxidase / phagocytosis and lysis of bacteria

Question 11

1. Name 3 reactive oxygen species (bad unavoidable products of mitochondrial respiration)
2. Two major disorders these cause
3. What removes this?

Answer 11

1. Superoxide radical, hydroxyl free radical, and hydrogen peroxide
2. Cancer and atherosclerosis
3. Antioxidants

Question 12

1. Name 3 nonenzymatic antioxidants

2. Name 3 enzymatic antioxidants

Answer 12

1. Vitamin E, vitamin C and beta carotene

2. Catalase, glutathione peroxidase (RBCs) and superoxide dismutase

Question 13

Importance of PPP for RBC

Answer 13

RBC can only produce NADPH by PPP

NADH is necessary to reduce glutathione and reduced glutathione is what prevents peroxides from accumulating

Question 14

Gluthathione removes peroxides via?

What happens if there is an accumulation of peroxides in RBCs

GSH vs GSSG

Answer 14

Glutathione peroxidase

RBCs become rigid, weakened cell walls (due to hgb oxidizing to methemogloblin), concomitant hemolysis

GSH is reduced; GSSG is oxidized

Question 15

Main function of the cytochrome P450 family of enzymes

Answer 15

Synthesizing and detoxifying reactions; making water soluble products so it can be excreted in urine (drugs/chemicals)

Question 16

1. Mitochondrial Cyt P450 mono oxygenase

2. Microsomal cyt P450 mono oxygenase

Answer 16

1. Steroid hormone, hormone and vitamin D metabolism, cholesterol synthesis
2. Smooth ER, detoxification

Question 17

1. A beneficial effect of ROS has to do with
2. Main mechanism
3. Why is it called a respiratory burst?

Answer 17

1. NADPH and phagocytosis by WBC (respiratory burst)
2. If you are are infected by bacteria, IgG will tag it and lysosome will attack. Once it is trapped, NADPH oxidase will produce superoxide H2O2 to kill bacteria
3. HR and respiration will increase because WBC need high concentration of OO2 to fight bacteria (to make H2O2)

Question 18

Genetic deficiencies of NADPH oxidase cause ____

How will this present clinically?

Answer 18

Chronic granulomatous disease (CGD)

Child that comes to clinic with chronic respiratory infections (will get sick even with the smallest exposure)

Question 19

1. NO pathway

2. Name 4 biological functions of Nitric Oxide (NO)

Answer 19

1. Arginine reacts with NADPH to synthesize NO
2. Relaxes smooth muscle, prevents clot formation, neurotransmitter in the brain, and released during inflammatory response to suppress it

Question 20

Glucose-6-phosphate dehydrogenase deficiency
(G6PD)

1. Affect in RBC
2. Symptoms?

Answer 20

1. Impairs the ability of RBC to form NADPH resulting in hemolysis
2. Most are asymptomatic unless exposed by oxidative stress

Question 21

Classifications of G6PD deficiency:

1. Class 1
2. G6PD mediterranean
3. G6PD A-

Answer 21

1. Rare and most severe / hemolytic anemia (very rigid RBCs)
2. Enzyme show normal stability but scarcely detectable activity in all RBCs
3. Enzyme is unstable but most of enzyme activity present in reticulocytes (immature RBCs) and younger RBCs

Question 22

What can cause G6PD patients to experience hemolysis

3 classes of oxidant drugs that can cause this; what are they and name some examples

Answer 22

Infection, fava beans, and oxidant drugs

Antibiotics- sulfa, chloramphenicol
Antimalarials- primaquin
Antipyretics- acetanilid

Question 23

How do G6PD patients with hemolytic anemia present?

Lab findings?

Answer 23

Pallor (anemia), slightly jaundiced sclera, and weak; recent travel to tropical regions

Low hematocrit, high blood levels of bilirubin, and hemoglobinuria

Question 24

What are Heinz bodies?

Answer 24

In G6PD, oxidation of SH groups cause these insoluble masses to attach to RBC membrane