HMP shunt Flashcards
describe hexose monophosphate shunt
- AKA pentose phosphate pathway
- Alternative pathway to glycolysis.
- Produce ribose-5 –phosphate and NADPH.
- Anabolic process
Where does it take place?
- Site : Occurs in all cells
- Subcellular cite : Cytosol
Irreversible Oxidative phase is highly active in?/ importance
Liver, lactating mammary glands & adipose tissue for NADPH- dependent biosynthesis of fatty acids.
❑ Testes, ovaries, placenta & adrenal cortex for NADPH-dependent biosynthesis of steroid hormones.
❑ RBCs for NADPH-dependent reduction of glutathione.
Products of Irreversible Oxidative phase :
2 NADPH
Ribulose-5-phosphate
CO2
which is the rate-limiting enzyme of the oxidative pathway?
Glucose 6-phosphate dehydrogenase
competitive inhibitor of G6PD?
NADPH
which co enzyme stimulates G6PD ?
NADP+
Describe the oxidative phase reactions (Irreversible)
The irreversible oxidative phase has 3 irreversible reactions. Used for NADPH-dependent biosynthesis
Steps:
- Glucose 6-P → 6-phosphoglucanolactone
- Enzyme: Glucose-6-P dehydrogenase
- Coenzyme: Mg2+
- NADP+ → NADPH + H+ - 6-phosphoglucanolactone → 6-phosphogluconate
- Enzyme: Glucanolactone hydrolase
- H2O → H+ - 6-phosphogluconate → Ribulose 5-phoasphate
- Enzymes: Phosphogluconate dehydrogenase
- Coenzyme: Mg2+
- NADP+ → NADPH + H+, and CO2
Total products of oxidative phase reactions in HMP shunt is 2 NADPH, Ribulose-5-phosphate and CO2.
Reversible Non-Oxidative phase reaction where?
-in all cell types synthesizing nucleotides and nucleic acids.
-Reactions catalyze the interconversion of sugars containing 3-7 carbons.
Significance of HMP shunt
-Production of NADPH.
* NADPH is a biochemical reductant.
-Production of ribose 5-phosphate.
* for nucleotide biosynthesis.
-Convert pentose sugars to triose and hexose intermediates of glycolysis.
Identify the role of NADPH in RBCs in connection to reduced glutathione
- Reduced Glutathione (GSH) can chemically detoxiy H2O2.
- H2O2 is one of the ROS that is formed from partial reduction of molecular oxygen. It can cause chemical damage to DNA and unsaturated lipids and leads to cell death
- The cell regenerates reduced glutathione (GSH) in a reaction catalyzed by glutathione reductase, using NADPH as a source of reducing equivalents.
- Hence, NADPH helps reduce H2O2 (through creating reduced glutathione) and therefore is protective.
Identify the role of NADPH in the respiratory burst mechanism of WBCs (emphasis on chronic granulomatous disease)
- Respiratory burst is a rapid inrease in the production of reactive oxygen species(ROS) during the phagocytosis of microbes. The ROS are useful in breaking down the bound material and killing micro-organisms.
- O2 is converted into O2- with the assistance of NADPH. This then becomes H2O2 and HOCl. Altogether, the ROS and HOCl are effecting in killing microorganisms during respiratory burst.
Chronic granulomatous disease (CGD)
- Rare inherited blood disorder caused by NADPH oxidase deficiency.
- Efficacy of phagocytes is reduced since there is reduced production of ROS and HOCl (which are responsible for killing microbes).
- Patients suffer severe repeated bacterial infections
- Test: nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) and genetic testing.
- Current therapy :antimicrobial and prophylaxis, early treatment of infections, and interferon gamma.
Role of NADPH in reductive biosynthesis- fatty acids
and cholesterol.
- Fatty acids and cholesterol synthesis require electron donors.
- Both are synthesized from acetyl-CoA and requires NADPH (as an electron donor).
- NADPH act as an electron donor.
Mention the role of NADPH in cytochrome P450 monooxygenase system
The P450 monooxygenase system is the primary enzyme system responsible for the oxidative metabolism of a variety of xenobiotics and endogenous compounds including drugs, carcinogens, fatty acids and hormones.
During CYP hydroxylation, one O atom from O2 is incorporated as a substrate’s hydroxyl group.
The second O atom is reduced by NADPH to water (H2O).
In the mitochondria:
- NADPH helps metabolize hydroxylate steroid hormones and Vitamin D
In microsomal (fragment of endoplasmic reticulum, with ribosome attached to microsome) regions:
- NADPH helps with detoxification of xenobiotic for two-fold purposes.
Mention the role of NADPH in Nitric oxide (NO) synthesis
- NO is synthesized from arginine, O2, and NADPH.
- FMN, FAD, heme, and tetrahydrobiopterin are coenzymes
- There are 3 NO synthase types which are encoded by different genes (neural nNOS, inducible iNOS, and endothelial eNOS).
- eNOS and nNOS are Ca2+-calmodulin depdenent
- iNOS is a Ca2+ indepdent enzyme - NO functions:
- Relaxes smooth muscles
- Prevents platelet aggregation
- It is a n.t in the brain
- Tumoricidal and Bactericidal.
