Hexose Monophosphate Pathway or HMP shunt

The pentose phosphate pathway (or HMP pathway) is an alternative route for the metabolism of glucose, which generates NADPH and ribose.

No ATP is used or produced.

serves two major functions:

1. production of NADPH as a reducing equivalent, and
2. synthesis of ribose 5-phosphate for nucleotide synthesis.

Transketolase is an enzyme of the 2nd stage of the pentose phosphate pathway. It requires thiamine pyrophosphate as a cofactor. Genetic defects in transketolase, or thiamine deficiency in alcoholics, result in Wernicke-Korsakoff syndrome, with its symptoms of memory loss and partial paralysis.

HMS in Erythrocyte

Erythrocytes utilize the reactions of the HMP shunt to generate large amounts of NADPH to maintain glutathione in a reduced state by the action of glutathione reductase. Reduced glutathione is important in protecting erythrocytes from oxidative damage resulting from oxidant drugs and oxidizing environmental toxins. In erythrocytes, the HMP shunt is the only major pathway that generates NADPH (no mitochondria, no ATP). Thus, defects in the oxidative portion of the HMP shunt result in poor protection of these cells against free radicals, hydrogen peroxide and other forms of oxidant stress.

G6PD deficiency

Heiz bodies formation

due to accumulation of H2O2 that creates disulfide covalent bonds between HbSH (sulphahydro) groups

makes junks attached to membrane leading to impaired membrane integrity => hemolysis