hmp shunt

Question 1

what is the function of hmp shunt? (2)

Answer 1

1. generate NADPH
2. generate ribose5P for purine nucleotide synthesis

Question 2

what are the pathways of glucose-6-p? (4)

Answer 2

1. glucose ↔ G6P (glycolysis/gluconeogenesis)
2. G6P→ pyruvate (glycolysis)
3. G6P ↔ glycogen (glycogen synthesis)
4. G6P→ HMP shunt

Question 3

where does HMP shunt occur? (tissues & organelle)

Answer 3

• cytoplasm
• active in tissues w high NADPH usage or in rapidly dividing cells requiring ribose-5-P for nucleic acid synthesis

glutathione reduction: RBC
FA synthesis: adipocytes, liver
steroid synthesis: adrenal cortex, gonads

H: hepatic
M: mammary glands
P: periphery of adrenal cortex

Question 4

what is the rate limiting enzyme of HMP shunt?

Answer 4

G6PD

Question 5

how is HMP shunt/G6PD regulated?

Answer 5

NADPH/NADP ratio: shortage of NADPH (NADPH/NADP ratio is low)→ activates shunt

Question 6

what is G6PD deficency?

Answer 6

• X-linked recessive disease (affects mostly males)
• diff G6PD mutations→ range of clinical symptoms (e.g. none to severe hemolytic anemia)
• G6PD deficiency→ lack of NADPH→ can’t maintain reduced glutathione→ oxidative stress in RBC→ hemolysis→ anemia & jaundice & kernicterus

Question 7

what is a potential advantage of G6PD deficiency?

Answer 7

• may confer resistance to malaria
• depletes NADPH→ decrease utilization by parasites for survival in RBCs

Question 8

what are the functions of NADPH? (5)

Answer 8

1. provides reducing power for biosynthesis (e.g. cholesterol synthesis)
2. provides reducing power for detoxification (e.g. liver)
3. generates ROS (e.g. WBCs) to kill bacteria
4. generates Nitric Oxide (bactericidal, vasodilative)
5. glutathione reduction (e.g. RBCs): 2GSH→ GSSG to convert H2O2→ H2O