The hexose monophosphate shunt

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Presentation transcript:

The hexose monophosphate shunt

The hexose monophosphate shunt: Overview

Reactions in the oxidative stage

Reactions in the sugar shuffle stage

Ketoses and aldoses in the HMS

The mechanism of transketolase

The mechanism of transaldolase

Why do we need both NADH and NADPH?

NADPH generation by malic enzyme

NADPH generation by transhydrogenase and NADP-linked isocitrate dehydrogenase

Uses of NADPH synthesis of fatty acids and cholesterol fixation of ammonia by glutamate dehydrogenase oxidative metabolism of drugs and poisons by cytochrome P450 enzymes generation of nitric oxide and of reactive oxygen species by phagocytes scavenging of reactive oxygen species that form as byproducts of oxygen transport and of the respiratory chain

Nitric oxide synthase requires NADPH

Signaling effects of nitric oxide

Phagocytes use NADPH to generate reactive oxygen species

Scavenging of reactive oxygen species requires NADPH, too

Glucose-6-phosphate dehydrogenase deficiency X-chromosomally encoded—males more severely affected most patients are healthy most of the time—hemolytic crises occur upon exposure to drugs or diet components that cause enhanced formation of ROS manifest in red blood cells because these cells lack protein synthesis—no replacement of deficient protein molecules affords partial protection against malaria—similar to sickle cell anemia and other hemoglobinopathias

Vicia faba and favism

Redox cycling of isouramil

Malaria parasites detoxify heme by crystallization

Primaquine and glucose-6-phosphate dehydrogenase deficiency