HMP PATHWAY

HEXOSE MONO PHOSPHATEPATHWAY

INTRODUCTION This pathway is also known as HMP

shunt/pentose phosphate pathway(PP Pathway).

Principal pathway for oxidation of glucose is glycolyis & TCA.

Discovered by Site :In the cytoplasm of all cells except

muscle, and non-lactating mammary gland T(low activity).

OBJECTIVESTo understand the function of

the pentose phosphate pathway in production of NADPH and ribose precursors for nucleic acid synthesis.

To examine the importance of NADPH in protection of cells against highly reactive oxygen species.

To relate defects in the pentose phosphate pathway which can cause disease.

IMPORTANCE OF NADPH

for reductive synthesis of fatty acids,

steroids, amino acids

via glutamate dehydrogena

se & production of

reduced glutathione in erythrocytes

and other cells.

Production of ribose

residues for nucleotide and nucleic

acid synthesis

for H2O2 eliminatio

n from body.

As a energy

molecule.

PP pathway is divided into 2 phase-1. Oxidative phase.

Reactions producing NADPH Irreversible

2.Non-oxidative phase Produces ribose-5-P Reversible reactions feed to glycolysis

Regulatory enzyme

NADPH + H+ is formed from two separate reactions.

The glucose 6-phosphate DH (G6PD) reaction is the rate limiting step and is essentially irreversible.

Cells have a greater need for NADPH than ribose 5-phosphate.

active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testes, and lactating mammary gland.

Transketolase requires the coenzyme thiamine pyrophosphate (TPP), the transaldolase does not.

- not active in non-lactating mammary gland and has low activity in skeletal muscle

Transketolase (TPP) and transaldolase are the link back to glycolysis.Glyceraldehyde 3-phosphateFructose 6-phosphate

Net result:3C5 2C6 + C3

IN THE MUSCLE

HMP Shunt inactive because G 6P Dehydrogenase and 6 P Gluconate Dehydrogenase deficient So they act as checkers for NADPH production.

ribose 5 P synthesized in the way of reverse HMP Shunt or through Transketolase path.

Glucose-6-phosphate dehydrogenase (G6PD)

deficiency causes hemolytic anemia

Mutations present in some populations causes a deficiency in glucose 6-phosphate dehydrogenase, with consequent impairment of NADPH production.

Detoxification of H2O2 is inhibited, and cellular damage results - lipid peroxidation leads to erythrocyte membrane breakdown and hemolytic anemia.

Most G6PD-deficient individuals are asymptomatic - only in combination with certain environmental factors (sulfa antibiotics, herbicides, antimalarials, *divicine) do clinical manifestations occur.

*toxic ingredient of fava beans

Glyceraldehydes 6Phosphate Dehydrogenase(G6PD) deficiency is a X-linked recessive hereditary disease which is due to deficiency Of G6PD,which is req. for RBC metabolism

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