CHAPTER 22: Unit 6. The Pentose Phosphate Pathway

Pentose Phosphate Pathway a metabolic pathway, alternative to that of glycolysis, of carbohydrate interconversion: hexose-6-phosphate is converted into pentose phosphate and carbon dioxide. The principal functions of the pathway are the production of deoxyribose and ribose sugars for nucleic acid synthesis; the generation of reducing power in the form of NADPH for fatty acid and/or steroid synthesis; and the interconversion of carbohydrates. Parts of the pathway are involved in the Calvin cycle in photosynthesis.

The pentose phosphate pathway is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses as well as ribose 5-phosphate, a precursor for the synthesis of Nucleotides. While the pentose phosphate pathway does involve oxidation of glucose, its primary role is anabolic rather than catabolic.

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https://www.youtube.com/watch?v=bgu3_WJY62w

The pentose phosphate pathway is primarily catabolic and serves as an alternative glucose oxidizing pathway for the generation of NADPH that is required for reductive biosynthetic reactions such as those of cholesterol biosynthesis, bile acid synthesis, steroid hormone biosynthesis, and fatty acid synthesis. The pentose phosphate pathway can also function as an anabolic pathway that utilizes the six carbons of glucose to generate five carbon sugars, particularly ribose-5-phosphate (R5P) that is required for purine and pyrimidine nucleotide biosynthesis. The pentose phosphate pathway can, under certain conditions, completely oxidize glucose to CO₂ and water. The primary functions of this pathway are:

1. To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.
2. To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
3. Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolyticand /or gluconeogenic intermediates.

Enzymes that function primarily in the reductive direction utilize the NADP⁺/NADPH co-factor pair as their co-factors as opposed to oxidative enzymes that utilize the NAD⁺/NADH co-factor pair. The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis and lactating mammary gland have high levels of the PPP enzymes. In fact 30% of the oxidation of glucose in the liver occurs via the PPP. Additionally, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione (see below). The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source, therefore, any rapidly proliferating cell needs large quantities of NADPH.

Although the PPP operates in all cells, with high levels of expression in the above indicated tissues, the highest levels of PPP enzymes (in particular glucose 6-phosphate dehydrogenase) are found in neutrophils and macrophages. These leukocytes are the phagocytic cells of the immune system and they utilize NADPH to generate superoxide radicals from molecular oxygen in a reaction catalyzed by the NADPH oxidase complex. Superoxide anion, in turn, serves to generate other reactive oxygen species (ROS) that kill the phagocytized microorganisms. Following exposure to bacteria and other foreign substances there is a dramatic increase in O₂ consumption by phagocytes. This phenomenon is referred to as the oxidative burst or respiratory burst.

Reference:https://rgd.mcw.edu/rgdweb/pathway/pathwayRecord.html?processType=view&species=Rat&acc_id=PW:0000045

Reference: https://aklectures.com/lecture/pentose-phosphate-pathway/introduction-to-pentose-phosphate-pathway

The pentose phosphate pathway of hexose monophosphate shunt is the alternative pathway of glycolysis to form simple sugar. It produces sugar for DNA formation. It also occurs in the cytoplasm of the cell. Steps of pentose phosphate are as follows:Oxidative phase It occurs in two steps where the first product of glycolysis is used.Glucose-6-phosphate oxidize to produce phosphogluconolactone and NADPH.Phosphogluconolactone decarboxylate and reduced to form 5 carbon compound i.e., ribulose 5 phosphate.It is the irreversible reaction. Nonoxidative phaseIt is the reversible process.In this process, ribulose-5-phosphate isomerizes to form two different sugars i.e., xylulose-5-phosphate and ribose-5-phosphate.These two sugars combine in the presence of transketolase and produce sedoheptulose-7-p and 3-phosphoglyceraldehyde.Sedoheptulose-7-p and 3-phosphoglyceraldehyde further combine to form fructose-6-p and erythrose-4-p.When erythrose-4-p combines with the xylulose-5-p in the presence of transketolase produces fructose-6-p and 3-phosphoglyceraldehyde.3-phosphoglyceraldehyde enters into the glycolysis and fructose-6-phosphate isomerises to form glucose-6-phosphate.

Reference: https://www.toppr.com/content/concept/pentose-phosphate-pathway-201449/

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