PENTOSE PHOSPHATE SHUNT or HEXOSE MONOPHOSPHATE PATHWAY This pathway consists of two parts: 1) Glucose-6-P undergoes two oxidations by NADP +, the second is an oxidative decarboxylation that forms a pentose-P. 2) The P-pentoses that are formed during the first part are transformed into glucose-6-P. Ferchmin )Pentose phosphate pathway or shunt (PPP). 2) Oxidative and isomerization parts. 3) Regulation 4) Metabolic roles of PPP 5) Reduction of glutathione. In glycolysis there was no net oxidation/reduction only “reshuffling” of the redox state of the carbons Part of glucose was not metabolized through glycolysis but through “a shunt” involving pentoses 1

GPDH deficiency is relatively common in persons with roots from regions with endemic malaria. In glycolysis followed by TCA (Kreb’s) cycle the first Cs to be converted to CO 2 are # 3 and 4. In PPP is C #1. 2

2) Nonoxidative steps of pentose phosphate shunt Positive regulator of lipid synthesis transketolase requires thiamine pyrophosphate (vitamin B1) transketolase requires thiamine pyrophosphate (vitamin B1) 3

GSSG is oxidized and GSH reduced glutathione which will be discussed in next page 4

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Glutathione synthesis is not ribosomal and glutathione is not directly encoded in DNA. Notice the unusual bonds between cysteine and glutamate. Unusual “peptide” bond. The pentose phosphate pathway (PPP) was explained in the previous slides. The next three slides address the anti-oxidative role of the PPP 6

Conceptual link between the NADPH+ + H dehydrogenases and glutathione reductase. The sketch below is not a real metabolic pathway just an illustration. 7

Glutathione peroxidase has selenocysteine a rare amino acid that contains selenium. The story of selenocysteine incorporation into proteins is unusual and exciting. There are many antioxidants that neutralize the oxygen reactive species (ROS). Among them are: vitamins C and E and recently the tomato red pigment, lycopene. Lycopene, became notorious for reportedly preventing prostate cancer and retinal macular degeneration. Proposed mechanism of glutathione peroxidase 8