Glycolysis reversal

Scheme 9.5 Multi-step enzymatic process for 2 -deoxyribo-nucleoside production from glucose, acetaldehyde and a nucleobase through glycolysis, reverse reactions of 2 -deoxy-ribonucleoside degradation and ATP regeneration by the yeast glycolytic pathway recycling the phosphate generated by nucleoside phosphorylase.

This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

The net free energy change, AG°, for this conversion is —37.7 kj/mol. The consumption of a total of six nucleoside triphosphates drives this process forward. If glycolysis were merely reversed to achieve the net synthesis of glucose from pyruvate, the net reaction would be... 

Glycolysis is a ten-step process that begins with isomerization of glucose from its cyclic hemiacetal form to its open-chain aldehyde form—a reverse nucleophilic addition reaction. The aldehyde then undergoes tautomerixa-tion to yield an enol, which undergoes yet another tautomerization to give the ketone fructose. 

Following hydrolysis, keto-enol tautomerization of the carbonyl group from C2 to Cl gives glucose 6-phosphate. The isomerization is the reverse of step 2 in glycolysis. 

Why aren t the glycolysis and gluconeogenesis pathways the exact reverse of one another ... 

Several Candida spp. will metabolise hydrocarbons to produce fumaric add the exact process is not fully worked out although glycolysis and reverse TCA are central features of the biochemistry of the process. 

Therefore, since step-growth polymers are often prepared by reversible reactions, it is feasible to convert them back to their monomers or ohgomers/chemicals by solvolytic processes such as hydrolysis, glycolysis,... 

Thermodynamic Barriers Prevent a Simple Reversal of Glycolysis... 

Three nonequilibrium reactions catalyzed by hexoki-nase, phosphofructokinase, and pyruvate kinase prevent simple reversal of glycolysis for glucose synthesis (Chapter 17). They are circumvented as follows ... 

The convetsion of fructose 1,6-bisphosphate to fructose 6-phosphate, to achieve a reversal of glycolysis, is catalyzed by fructose-l,6-bi pho pbatase. Its ptesence determines whether or not a tissue is capable of synthesizing glycogen not only from pymvate but also from ttiosephosphates. It is present in hvet, kidney, and skeletal muscle but is probably absent from heart and smooth muscle. 

The pathway of gluconeogenesis in the liver and kidney utilizes those reactions in glycolysis which are reversible plus four additional reactions that circumvent the irreversible nonequilibrium reactions. 

Figure 20-h Flow chart of pentose phosphate pathway and its connections with the pathway of glycolysis. The full pathway, as indicated, consists of three interconnected cycles in which glucose 6-phosphate is both substrate and end product. The reactions above the broken line are nonreversible, whereas all reactions under that line are freely reversible apart from that catalyzed by fructose-1,6-bisphosphatase. 

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

All of the glycolysis reactions ranging from phosphoenolpyruvate to fructose 1,6-bisphosphate are reversible, and the phosphoenolpyruvate molecules formed are consumed for producing fructose 1,6-bisphosphate by making use of the same glycolysis enzymes. 

As far as I can judge, all primitive cells had a basic reducing cell metabolism glycolysis, a citric acid cycle or its reverse, amino acid and base synthesis, while all maintained high K+, low Na+ and Cl-, moderate Mg2+, and very low Ca2+ (see Figure 2.3) by input and output pumps. Chemical... 

L-Galactose is probably not produced from L-glycerose, since the latter inhibits glycolysis and, even so, reaction with dihydroxyacetone phosphate in the presence of aldolase yields L-sorbose 1-phosphate which, on stereochemical grounds, is also an unlikely precursor. A more plausible route is direct conversion from D-galactose (XXI) by complete reversal of stereo-... 

Glucose 6-phosphate to and from glycolysis and gluconeogenesis Glucose 6-phosphate to pentose phosphates (not reversible)... 

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