Metabolism hydrogen based

Abnormalities of acid-base status of the blood are always accompanied by characteristic changes in electrolyte concentrations in the plasma, especially in metabolic acid-base disorders. Hydrogen ions cannot accumulate without concomitant accumulation of anions, such as CL or lactate, or without exchange for cations, such as or NaL Consequently, electrolyte composition of blood serum or plasma is often determined along with measurements of blood gases and pH and to assess acid-base disturbances. 

Metabolic acid-base disorders are those which directly cause a change in the bicarbonate concentration. Examples incluile diabetes mcliitus. where altered intemiediary metabolism in the absence of insulin cau.ses a build up of hydrogen ion from the ioni/ation of aceloacetic and P-hydroxybutyric acids, or loss of bicarbonate from the extracellular Iluid. e.g. from a duodenal fistula. 

Primary problems with hydrogen ion production or excretion are reflected in the IHCO,"] and these are called metabolic acid-base disorders. 

Although, salen Mn complexes for therapeutic use were originally conceived as SOD mimetics, it soon became clear that EUK-8 also exhibited catalase activity, the ability to metabolize hydrogen peroxide (75). The catalase activity of EUK-8 was not unexpected, since Mn porphyrins had been studied as catalase models by the Meunier laboratory (16) and, like the porphyrins, salen ligands form stable complexes with Mn(III) (6). As described previously (77), similar to that of mammalian heme-iron based catalases (78), the catalase activity of salen Mn complexes is not saturable with respect to hydrogen peroxide. As has been reported for protein catalases (18), salen Mn complexes exhibit peroxidase activity, in the presence of an electron donor substrate, as an alternative to a catalatic pathway. This supports the analogy between the behavior of these mimetics and that of catalase enzymes, and is consistent with the following mechanistic scheme (76,17) ... 

Citrate synthase catalyzes the metabolically important formation of citrate from ace-tyl-CoA and oxaloacetate [68]. Asp-375 (numbering for pig CS) has been shown to be the base for the rate-limiting deprotonation of acetyl-CoA (Fig. 5) [69]. An intennediate (which subsequently attacks the second substrate, oxaloacetate) is believed to be formed in this step the intermediate is thought to be stabilized by a hydrogen bond with His-274. It is uncertain from the experimental data whether this intermediate is the enolate or enol of acetyl-CoA related questions arise in several similar enzymatic reactions such as that catalyzed by triosephosphate isomerase. From the relative pK values of Asp-375... 

The fact that a Lewis acid is able to accept an electron pair means that it must have either a vacant, low-energy orbital or a polar bond to hydrogen so that it can donate H+ (which has an empty7 Is orbital). Thus, the Lewis definition of acidity includes many species in addition to H+. For example, various metal cations, such as Mg2+, are Lewis acids because they accept a pair of electrons when they form a bond to a base. We ll also see in later chapters that certain metabolic reactions begin with an acid-base reaction between Mg2+ as a Lewis acid and an organic diphosphate or triphosphate ion as the Lewis base. 

Several types of atoms in addition to hydrogen can be detected by MRI, and the applications of images based on 31P atoms are being explored. The technique holds great promise for studies of metabolism. 

Chemoreceptor response to increased arterial hydrogen ion concentration. An increase in arterial hydrogen ion concentration, or a decrease in arterial pH, stimulates the peripheral chemoreceptors and enhances ventilation. This response is important in maintaining acid-base balance. For example, under conditions of metabolic acidosis, caused by the accumulation of acids in the blood, the enhanced ventilation eliminates carbon dioxide and thus reduces the concentration of H+ ions in the blood. Metabolic acidosis may occur in patients with uncontrolled diabetes mellitus or when tissues become hypoxic and produce lactic acid. An increase in arterial hydrogen ion concentration has no effect on the central chemoreceptors. Hydrogen ions are unable to cross the blood-brain barrier. 

Once the protein interaction pattern is translated from Cartesian coordinates into distances from the reactive center of the enzyme and the structure of the ligand has been described with similar fingerprints, both sets of descriptors can be compared [25]. The hydrophobic complementarity, the complementarity of charges and H-bonds for the protein and the substrates are all computed using Carbo similarity indices [26]. The prediction of the site of metabolism (either in CYP or in UGT) is based on the hypothesis that the distance between the reactive center on the protein (iron atom in the heme group or the phosphorous atom in UDP) and the interaction points in the protein cavity (GRID-MIF) should correlate to the distance between the reactive center of the molecule (i.e. positions of hydrogen atoms and heteroatoms) and the position of the different atom types in the molecule [27]. 

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