Pentose Phosphate Pathway(Hexose monophosphate Shunt)

• Overview• Oxidative branch of

Glucose• Non-oxidative:

Regeneration• Modes• Red Blood cells• Glucose 6-P

dehydrogenasedeficency

• White blood cells

Overview • oxidizes Glucose • located in cytoplasm • produce NADPH for

reductiive biosynthesis• Ribose 5-P for biosynthesis

of nucleotides and amino acids

• occurs adipose, mammary, ovary, testes, adrenal gland, bone marrow, skin, intestinal mucosa– can account for over 30% of

flux of glucose • Two parts

– oxidative – non-oxidative

Oxidative branch

• Three steps • Glucose 6-P

dehydrogenase is committing step

• Produces 2 NADPH, 1 CO2, 1 Ribose 5-P

• Fourth step is isomerase of Ribulose to Ribose

Glu 6-P + 2NADP+ H2O ribose 5-P + 2NADPH + CO2 + H+

Non-oxidative Branch

• Reversible • Interconverts

3,4,5,6,7 carbon sugars for synthesis of other compounds

• Transketolase• Transaldolase

Steps: Non-oxidative Branch

Transketolase

Stabilization

Transketolase

Transaldolase

Transaldolase

Summary

Modes of Pentose PathwayDependent on cytoplasmic concentration of NADP+

Liver cell NADP+ / NADPH = 0.014 while NAD+/NADH = 700

Role of Pentose Pathway

Red Blood cells

• detoxify oxidation products

• reduce sulfhydral groups in hemoglobin, if not cross link to form Heinz bodies

• Keep Fe+2

• maintain structure of RBC • Also, required lens and

cornea of eye

Mechanism

• NADPH reduces Glutathione

• Glutathione reductase catalyses reaction

• Peroxide inactivation

Role of Glutathione

Vicia faba (fava beans) containspamaquine

Glucose 6-P dehydrogenasedeficiency

• sex-linked trait (11% of NA africanamericans, 5-10% of mediteraneanand Middle eastern heritage

• cause oxidative stress under certain environmental conditions

• low levels of glutathione • another genetic trait favored in

malarial regions • Falciparum malaria • distorts surface of red blood cells • targets them for destruction • anit-malarial drugs cause hemolytic

crisis by oxdiative stress • Can survive under normal

conditions

White blood cells • generates oxidizing

agents • NADPH oxidase• phagolysosomes and

myeloperoxidase• Chronic granulomatous

disease (CGD) fail to activate NADPH oxidase

• Due to lack of activation of enzyme/activating system

• Recurrent bacterial and fungal infections