HMP shunt

Question 1

What does the HMP shunt/pentose phosphate pathway do

Answer 1

• Produce source of NADPH from abundantly available G6P
• makes ribose for nucleotide synthesis
• has oxidative and nonoxidative phase, both in cytosol
• no ATP used or made

Question 2

Where does HMP shunt happen

Answer 2

• liver
• lactating mammary glands
• adrenal cortex (sites of FA or steroid synthesis)
• RBCs

Question 3

What is NADPH required for

Answer 3

Reductive reactions

1. glutathione reduction inside RBCs - detoxifies free radicals and peroxides
2. FA and cholesterol biosynthesis

Question 4

Which phase of HMP shunt is irreversible

Answer 4

Oxidative

G6P to CO2, 2NADPH, ribulose-5-P

via G6P DH

Question 5

Which phase of HMP shunt is reversible

Answer 5

nonoxidative

Ribulose-5-P to/from ribose-5-P, glyceradlehyde-3-P, fructose6P

via phosphopentose isomerase, transketolase

Question 6

Decrease in NADPH in RBCs can lead to

Answer 6

hemolytic anemia

poor RBC defense against oxidizing agents (fava beans sulfa, nitrofurantoin, primaquine/chloroquine, anti-TB drugs)

Question 7

MCC of precipitant of hemolytic anemia

Answer 7

infection

• inflammatory response makes free radicals that diffuse into RBCs causing oxidative damage

Question 8

What are some characteristics of G6PD deficiency

Answer 8

• XR
• MC human enzyme deficiency
• prevalent in african americans
• increase malarial resistance
• Heinz bodies =denatured globin chains precipitate within RBCs from ox. stress
• Bite cells = phagocytic removal of Heinz bodies by splenic macrophages

Question 9

What 3 pathways can Glucose-6-phosphate go into

Answer 9

1. Glycolysis
2. HMP shunt
3. Glycogen storage

Question 10

Transketolase needs what to work

Answer 10

Thiamine pyrophosphate (TPP)

Ribose-5-P <—>Glyceraldehyde-3-phosphate

Question 11

What enzyme must work for proper brain function

Answer 11

transketolase

Question 12

What are the 4 TPP requiring enzymes

Answer 12

2, 3, and 4 also require “tender, loving, care, for nancy”

1. Transketolase
2. PDH
3. alpha-ketoglutarate DH (TCA)
4. Brached chain ketoacid DH (Maple syrup disease)

Question 13

What genetic disorder involves a defect in transketolase

Answer 13

Wernicke-Korsakoff disease

point mutation in TPP gene

TPP can’t bind to transketolase as well

Brain doesn’t work as well as it should

Question 14

How is Beri Beri different from Wernicke-Korsakoff syndrome

Answer 14

Beri Beri cannot use all 4 TPP requiring enzymes

WK syndrome cannot use transketolase