Reactions, priming metabolic

FIGURE 14.2 The breakdown of glucose by glycolysis provides a prime example of a metabolic pathway. Ten enzymes mediate the reactions of glycolysis. Enzyme A, fructose 1,6, hiphos-phate aldolase, catalyzes the C—C bondbreaking reaction in this pathway. 

Clara cells have also been shown to have additional functions besides secretion. That is, these cells appear to be prime sites of xenobiotic metabolism in the lung via cytochrome P4go-dependent hydroxylation reactions (Serabjit-Singh et al, I960 Devereaux et al., 1984). Thus, the Clara cells may also be important in the detoxification of inhaled foreign substances. 

The reaction of carbamoyl phosphate with aspartate to produce W-carbamo-ylaspartate is the committed step in pyrimidine biosynthesis. The compounds involved in reactions up to this point in the pathway can play other roles in metabolism after this point, A -carbamoylaspartate can be used only to produce pyrimidines—thus the term committed step. This reaction is catalyzed by aspartate transcarbamoylase, which we discussed in detail in Ghapter 7 as a prime example of an allosteric enzyme subject to feedback regulation. The next step, the conversion of A-carbamoylaspartate to dihydroorotate, takes place in a reaction that involves an intramolecular dehydration (loss of water) as well as cyclization. This reaction is catalyzed by dihydroorotase. Dihydroorotate is converted to orotate by dihydroorotate dehydrogenase, with the concomitant conversion of NAD to NADH. A pyrimidine nucleotide is now formed by the reaction of orotate with PRPP to give orotidine-5 -monophosphate (OMP), which is a reaction similar to the one that takes place in purine salvage (Section 23.8). Orotate phosphoribosyltransferase catalyzes this reaction. Finally, orotidine-5 -phosphate decarboxylase catalyzes the conversion of OMP to UMP... 

During the conversion of one molecule of glucose to two molecules of pyruvate, two molecules of ATP are used to prime reactions 1 and 3 but, since reactions 5-9 occur twice over, for every molecule of glucose metabolized, a total of four molecules of ATP are produced, two each in reactions 6 and 9, giving a net synthesis of two molecules of ATP. Thus the overall reaction is... 

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