HMP shunt pathway

Importance of HMP-Shunt:

1. Provides ribose sugar for synthesis of nucleotide and nucleic acid.

2. Provides NADP2H to:

·        Helps in reductive synthesis of fatty acid, steroid, cholesterol etc.

·        Support detoxifying functions of liver by hydroxylation of toxic water insoluble aromatic/ aliphatic substances into water soluble, less toxic or nontoxic forms.

·        Prevent hemolysis by facilitating antioxidant activity in RBC.

·        Facilitate superoxide and free radical production in phagocytes through oxygen dependant myeloperoxidase system to kill bacteria and other pathogens.

·        Help in reduction of H₂O₂.

·        Help in synthesis of nitric oxide or endothelial derived relaxing factor.

3. It is an alternative pathway of glucose oxidation.

Discuss the role of HMP shunt in relation to anti-oxidant activity in RBC.

Under the influence of different oxidants, hemoglobin in RBC may turn into methemoglobin, where ferrus iron of normal hemoglobin is converted to ferric form by losing one electron which is accepted by molecular oxygen to form superoxide. This superoxide causes lysis of RBC membrane and the methemoglobin that is produced loses oxygen carrying capacity. Therefore to save RBC, superoxide must be metabolized to H₂O and to maintain normal hemoglobin function methemoglobin must be converted back to normal hemoglobin. For these activities NADP2H provided by HMP shunt is needed.

Mention the importance of HMP shunt and explain why enzyme deficiency of shunt causes hemolytic anemia.

Importance of HMP shunt:

a. Provides ribose sugar for synthesis of nucleotide and nucleic acid.

b. Provide NADPH to

·        Helps in reductive synthesis of fatty acid, steroid, cholesterol etc

·        Support detoxification of toxic water insoluble aromatic/aliphatic substances into water soluble less toxic or non toxic forms

·        Prevent hemolysis by facilitating antioxidant activity in RBC

·        Facilitate superoxide and free radical production in phagocytes through oxygen dependent myeloperoxidase system to kill bacteria and other pathogens

·        Helps in reduction of H₂O₂.

·        Helps in synthesis of NO and EDRF

c. It is alternative pathway of glucose oxidation.

Clinical consequence of G6PD deficiency:

Hemolytic anemia: here HMP shunt cannot continue to provide NADP2H because of the deficiency of its rate limiting enzyme G6PD. So hemolytic anemia happens to occur due to the failure of superoxide metabolism in RBC due to the lack of NADP2H.