Glycolysis proton production

Exercise increases the activity of the purine nucleotide cycle, which converts aspartate to fumarate plus ammonia (see Fig. 41.13). The ammonia is used to buffer the proton production and lactate production from glycolysis, and the fumarate is recycled and can form glutamine. 

An important point to note is that this the above reaction produces lactate, not lactic acid. Nonetheless, protons are produced in glycolysis but in another reaction (Appendix 6.5). Consequently, the two end-products are lactate plus protons, which can be described as lactic acid. Despite this discussion, it can be argued that lactate dehydrogenase is not the terminal reaction of glycolysis, since the lactate plus protons have to be transported out of the cell into the interstitial space. This requires a transporter protein, which transports both lactate and protons across the plasma membrane and out of the cell. 

Transaldolase catalyzes the transfer of a C3 unit. The reaction occurs via an aldol cleavage similar to that seen with aldolase there is a schiff base intermediate formed with an active site lysine. The difference between aldolase and transaldolase is in the acceptor groups in aldolase the acceptor is a proton, in transaldolase it is another sugar. This reaction yields a F-6-P, which can go to Glycolysis, and an E-4-P which reacts with Xu-5-P catalyzed by the same transketolase seen above. This second transketolase reaction yields F-6-P and Ga-3-P, both intermediates of Glycolysis and the end products of the Pentose-P pathway. 

As was true in step 4 of glycolysis (Figure 29.4), this aldol reaction actually takes place not on the free ketone but on an imine (Schiff base) formed by reaction of dihydroxyacetone phosphate with a side-chain -NH2 group on the enzyme. Loss of a proton from the neighboring carbon then generates an enamine (Section 19.9), an aldol-like reaction ensues, and the product is hydrolyzed. 

That lactic acid is the end product of anaerobic glycolysis in muscle tissue has been known for all of this century (Fig. 1). Cell-free extracts able to catalyze the oxidation of lactate to pyruvate were first obtained in 1932 (5). Warburg (6) and von Euler (7) and their colleagues discovered the above reaction [Eq. (1)] and associated it with the chemical properties of a coenzyme. Racker (8) demonstrated in 1950 that the forward reaction also involved the release of a proton. The first purified enzyme was reported by Straub (9) in 1940, while the first micrographs of LDH crystals were shown by Kubowitz and Ott (10). 

Additionally, this cyclopropane is set in conjugation with the C5-C6 insaturation in such a way that the bisected geometry derived from its spyrocyclic disposition maximizes the overlap between the n and cyclopropane 3d molecular orbitals. The setting is ideal for the constitution of a non-classical carbenium ion (8) if a proton is trapped by the C5-C6 double bond, Fig (5) route A. The nucleophilic attack of water from the medium would yield the rupture of the cyclopropane unit, and water elimination from the tertiary alcohol in the resulting diol (9) would furnish a conjugated dienone (10). Aromatization to the observed product, pterosin B (11), would occur by acid-induced glycolysis. Conversely,... 

Salicylate, which is a degradation product of aspirin in the human, is lipid soluble and has a dissociable proton. In high concentrations, as in salicylate poisoning, salicylate is able to partially uncouple mitochondria. The decline of ATP concentration in the cell and consequent increase of AMP in the cytosol stimulates glycolysis. The overstimulation of the glycolytic pathway (see Chapter 22) results in increased levels of lactic acid in the blood and a metabolic acidosis. Fortunately, Dennis Veere did not develop this consequence of aspirin poisoning (see Chapter 4). 

One of the early findings in experimental ischemia was the production of lactate and a concomitant proton which leads to tissue acidification (Lowry et al., 1964). The activation of anaerobic glycolysis produces tissue acidification which led to an... 

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