HMP Flashcards
What is the purpose of HMP?
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
Glucose 6-phosphate dehydrogenase (G6PD)
first enzyme in HMP pathway
What are the 2 phases of HMP?
Which uses ATP?
oxidative and non-oxidative;
neither uses ATP
How many irreversible steps are in the oxidative phase?
3 irreversible steps followed by isomerization of ribulose 5-phosphate to ribose 5-phosphate (R5P)
What is the stoichiometry for the oxidative phase?
(G6P) + (2 NADP+) + (H2O) –> (R5P) + (2 NADPH) + (2 H+) + CO2
What does 6-phosphgluconate dehydrogenase do?
enzyme responsible for irreversible conversion of 6-phosphogluconate to ribulose 5-phosphate
What are the enzymes that link the pentose phosphate path and glycolysis?
1) transketolase: transfers 2 carbons, utilizing thiamine pyrophosphate (TPP)
2) transaldolase: transfers 3 carbons
What regulates the HMP in the short term?
G6PDH (glucose 6-phosphate dehydrogenase) is the regulatory enzyme
What effect does NADPH have on G6PDH?
competitive inhibitor
What regulates the HMP in the long term?
insulin activates transcription of G6PDH
What happens in wenicke-korsakoff syndrome?
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
What is the fate of the pentose phosphate pathway if the cell needs….
NADPH only
(fatty acid synthesis; detoxification)
Fate of pathway:
- oxidative rxns produce NADPH,
- nonoxidative rxns convert ribulose 5-P to glucose 6-P to produce more NADPH
What is the fate of the pentose phosphate pathway if the cell needs….
NADPH + R5P
(rapidly dividing cells)
oxidative rxns produce NADPH and Ribulose 5-P;
the isomerase converts Ribulose 5-P to ribose 5-P (R5P)
What is the fate of the pentose phosphate pathway if the cell needs….
NADPH and pyruvate (RBCs)
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
What are the pathways requiring NADPH?
- 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)
What are the functions and tissues that use reductive biosynthesis (4 functions)
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)
Explain the mitochondrial system of cyto p450
1) Biosynthesis of steroid hormones (placenta, ovaries, testes, and adrenal cortex)
2) biosynthesis of bile acid and biologically active vit D3 (liver)
Explain the microsomal system of cyto p450
Detox (of foreign compounds (xenobiotics) - drugs, pollutants like petroleum and pesticides) -
via activations/deactivation of drug to make more soluble –> urine
How does reductive biosynthesis assist in killing bacteria?
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
How does reductive biosynthesis affect Nitric oxide production?
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
How does reductive biosynthesis affect reduction of hydrogen peroxide?
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
