Definition:
It is an alternative minor pathway for glucose oxidation.
Does not produce ATP nor utilize it.
Producing NADPH+H+, (Biosyn Lipids) and Ribose (Synthesis of NA).
Also called,
PPP (Pentose Phosphate Pathway)
HMP Shunt (Hexose Monophosphate Shunt)
Intracellular site and tissue distribution:
Cytosolic in tissues namely: liver, Adipose tissues, Lactating mammary gland, RBCs, Suprarenal cortex, Thyroid and testis.
Not active in non-lactating mammary gland, and in skeletal muscles.
Steps of HMP Shunt:
The pathway are divided into two phases:
1. Phase I : Oxidative irreversible phase
2. Phase II : Non-oxidative reversible phase.
Regulation of HMP shunt: -
The key regulatory enzymes are G-6-PD and 6-phospho-gluconate dehydrogenase.
They are activated by fed state, glucose, insulin, thyroxine and NADP.
But….
They are inhibited during starvation, diabetes mellitus and with high NADPH.H+/NADP ratio.
Significance of HMP Shunt:
I- Production of pentoses:
Tissues must satisfy their own requirement of pentoses since dietary pentoses are not utilizable and ribose is not a significant constituent of systemic blood.
Pentoses are used for:
1. Nucleic acids, Ribose for RNA and Deoxyribose for DNA.
2. Coenzymes synthesis, e.g., NAD+, FAD, CoASH.
3. Free nucleotide Coenzymes, e.g., ATP, GTP,
4. Synthesis of certain vitamins, e.g., B2 and B12.
II-HMP pathway is the major human source for production of NADPH.H+ required for:
1. Fatty acid synthesis (lipogenesis) and fatty acid
desaturation.
2. Cholesterol and other steroid synthesis.
3. Synthesis of sphingosine and cerebrosides.
4. Synthesis of non-essential amino acids, e.g.,
glutamate and tyrosine from phenylalanine.
5. Regeneration of reduced glutathione (G-S-H).
6. Metabolic hydroxylation with cyp450.
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