HMP

Question 1

What is the purpose of HMP?

Answer 1

1) produce cell’s basic anabolic reducing power: NADPH (reduced nicotinamide adenine dinucleotide phosphate)
2) synthesis of R5P (ribose 5-phosphate) - NB alternate routes exist for this synthesis

Question 2

Glucose 6-phosphate dehydrogenase (G6PD)

Answer 2

first enzyme in HMP pathway

Question 3

What are the 2 phases of HMP?

Which uses ATP?

Answer 3

oxidative and non-oxidative;

neither uses ATP

Question 4

How many irreversible steps are in the oxidative phase?

Answer 4

3 irreversible steps followed by isomerization of ribulose 5-phosphate to ribose 5-phosphate (R5P)

Question 5

What is the stoichiometry for the oxidative phase?

Answer 5

(G6P) + (2 NADP+) + (H2O) –> (R5P) + (2 NADPH) + (2 H+) + CO2

Question 6

What does 6-phosphgluconate dehydrogenase do?

Answer 6

enzyme responsible for irreversible conversion of 6-phosphogluconate to ribulose 5-phosphate

Question 7

What are the enzymes that link the pentose phosphate path and glycolysis?

Answer 7

1) transketolase: transfers 2 carbons, utilizing thiamine pyrophosphate (TPP)
2) transaldolase: transfers 3 carbons

Question 8

What regulates the HMP in the short term?

Answer 8

G6PDH (glucose 6-phosphate dehydrogenase) is the regulatory enzyme

Question 9

What effect does NADPH have on G6PDH?

Answer 9

competitive inhibitor

Question 10

What regulates the HMP in the long term?

Answer 10

insulin activates transcription of G6PDH

Question 11

What happens in wenicke-korsakoff syndrome?

Answer 11

transketolase that is defective in TPP binding (10x less effective than nromal)
can cause neuropsychiatric disorder

Sx: paralysis of eye movements, abnormal gait, decreased mental function, severely impaired memory

Question 12

What is the fate of the pentose phosphate pathway if the cell needs….

NADPH only
(fatty acid synthesis; detoxification)

Answer 12

Fate of pathway:

• oxidative rxns produce NADPH,
• nonoxidative rxns convert ribulose 5-P to glucose 6-P to produce more NADPH

Question 13

What is the fate of the pentose phosphate pathway if the cell needs….

NADPH + R5P
(rapidly dividing cells)

Answer 13

oxidative rxns produce NADPH and Ribulose 5-P;

the isomerase converts Ribulose 5-P to ribose 5-P (R5P)

Question 14

What is the fate of the pentose phosphate pathway if the cell needs….

NADPH and pyruvate (RBCs)

Answer 14

Both oxidative and nonoxidative pathways used.

The oxidative rxns generate NADPH and ribulose 5-P.
The nonoxidative rxns convert the ribulose 5-P to fructose 6-P and glyceraldehyde 3-P;
glycolysis converts these intermediates to pyruvate

Question 15

What are the pathways requiring NADPH?

Answer 15

1. Reductive biosynthesis,
   2) cytochrome P450 mono-oxygenase system;
   3) phagocytosis by WBC;
   4) synthesis of NO
   5) reduction of hydrogen peroxide (a reactive oxygen species)

Question 16

What are the functions and tissues that use reductive biosynthesis (4 functions)

Answer 16

1) Steroid synthesis (Adrenal gland, testis, ovaries)
2) FA synthesis (adipose tissue, mammary glands, liver)
3) cholesterol synthesis (liver)
4) maintenance of reduced glutathione (RBCs)

Question 17

Explain the mitochondrial system of cyto p450

Answer 17

1) Biosynthesis of steroid hormones (placenta, ovaries, testes, and adrenal cortex)
2) biosynthesis of bile acid and biologically active vit D3 (liver)

Question 18

Explain the microsomal system of cyto p450

Answer 18

Detox (of foreign compounds (xenobiotics) - drugs, pollutants like petroleum and pesticides) -

via activations/deactivation of drug to make more soluble –> urine

Question 19

How does reductive biosynthesis assist in killing bacteria?

Answer 19

phagocytosis by WBCs:

1) attachment of the pathogen to the phagocytic cell
2) ingestion of the microorganism
3) destruction of the microorganism:
- NADPH oxidase converts O2 into superoxide radical O2-

NB: O2-, H2O2, and HOCl are super toxic to microorganism

Question 20

How does reductive biosynthesis affect Nitric oxide production?

Answer 20

L-arginine –> L-citrulline

(using NO synthase: NADPH + (H+) gets swapped for NADP+ while O2 gets swapped for NO)

NB: NO relaxes smooth muscle, prevents platelet aggregation, fxns as brain NT, mediates tumoricidal and bactericidal actions of macrophages

Question 21

How does reductive biosynthesis affect reduction of hydrogen peroxide?

Answer 21

formation of reactive oxygen species:

can cause serious chemical damage to proteins, DNA, unsaturated lipids

Can cause cell death

implicated in pathological conditions such as cancer, aging, inflammation