Why is the hexose monophosphate shunt (pentose phosphate pathway) called a direct oxidative pathway( Ref. Biochemistry by Satyanarayana , 4th edition, pg.no: 244) , even though oxygen molecule is not used for oxidation? It uses NADP for its oxidation. So if utilisation of NADP is direct oxidation then what will be indirect oxidation? How can I differentiate direct and indirect oxidation? Is the use of Electron transport chain considered as secondary oxidation?
This answer is based on a 2002 autobiographical account of the work of Bernard L. Horecker entitled The Pentose Phosphate Pathway. Here he refers to “direct oxidative pathway” but does not unambiguously explain this, so I shall summarize my interpretation and then provide evidence in terms of quotations.
Summary of my interpretion of Horecker’s account
When what I shall initially refer to as the hexose monophosphate shunt (HMS) was being elucidated in the late 1930s and the 1940s it was thought that its main purpose was the same as that was envisaged for aerobic glycolysis — to oxidize glucose to provide energy — and was merely an alternative way of doing this. The term ‘direct oxidative pathway’ was used to distinguish it from the glycolytic pathway (then refered to as the Embden–Meyerhof–Parnas pathway), presumably because six cycles of the oxidative phase e could completely oxidize one molecule of glucose 6-phosphate to carbon dioxide, whereas glycolysis only oxidized it to pyruvate. Presumably this was regarded as ‘indirect oxidation’ because complete oxidation required the further metabolism of pyruvate using the tricarboxylic acid cycle.
The term ‘direct oxidative pathway’ fell out of use as it was realized that the main functions of the pathway were to provide pentoses for nucleic acid synthesis and NADPH for synthesis of fatty acids, steroids, and reduction of oxidized glutathione. It was for this reason also that the name most commonly used for the pathway changed to the pentose phosphate pathway, transfering the emphasis to one of the products.
Quotations from Horecker
…Haas arrived from Warburg’s laboratory in 1939. Haas asked me to join him in the search for an enzyme that would catalyze the reduction of cytochrome c by reduced TPN (now NADP). This reaction was thought to be the missing link in the electron transport chain from substrate to oxygen and marked the beginning of my interest in what was then thought to function as a direct oxidative pathway for the metabolism of carbohydrate but is now known as the pentose phosphate pathway…
…These observations gave rise to the hypothesis that the oxidative pathway was really a cyclic mechanism for the direct oxidation of carbohydrate. With each turn of the cycle one molecule of carbon dioxide would be produced, and the pentose phosphates formed would be metabolized back to hexose phosphates to start another cycle. Six turns of the cycle would result in the complete oxidation of one molecule of glucose…
…The function(s) of the new pathway, however, turned out to be quite different from the pathway for the direct oxidation of carbohydrate that we had expected. It provides two mechanisms for the production of ribose 5-phosphate. One is the “oxidative branch” of the pathway, which also generates 2 eq of TPNH (NADPH). Ribose 5-phosphate can also be formed directly from hexose and triose phosphates by the non-oxidative rearrangements catalyzed by transketolase and transaldolase. Where large quantities of NADPH are required, as in the synthesis of fatty acids or sterols, the excess pentose phosphates produced would be recycled back to hexose monophosphates.
Google Books ngrams of term usage
Addition of $O_2$ or removal of H means oxidation. In this process H is removed from sugar, added to NADP as well C is oxidised to $CO_2$. Hence , it is oxidation reaction.
HMP pathway is used to produce NADPH. The process directly oxidise glucose to $CO_2$ and $H_2O$. It does not require TCA cycle or ETC. Hence is called direct oxidative pathway.
Glycolysis on other hand does not produce any $CO_2$ and $H_2O$.Hence, is indirect, as it needs TCA and ETC for complete oxidation.
Source: Biochemistry U. Satyanarayan Edition: 2013 Pg: 244 and 245(written in brackets on Pg 245)