Propionic acid, differentiation from

Extraction of 25 different binary mixtures of racemic acids (2-(4-isobutylphenyl)-propionic acid (1), and cis- and trans-chrysanthemic (2)), and various chiral bases with supercritical carbon dioxide permitted the conclusion that molecular chiral differentiation in a supercritical fluid is more efficient than in conventional solvents. In the majority of cases, however, complete separation could not be achieved. In five cases, remarkable partial resolutions were realized (30-75% ee) and resolution was possible on a preparative scale. The pair ds-chrysanthemic acid and (S)-(-i-)-2-(benzylamino)-1-butanol (3) was studied in detail. Pressure, temperature, and time, as well as the molar ratio of base and acid, had a marked influence on the quantity and quality of the products. Increasing pressure or decreasing temperature resulted in higher ee values. (-)-cw-Chrysanthemic acid in 99% ee was obtained from the raffinate in a single extraction step. Multiple extractions produced the (-i-)-cA-acid in 90% ee (see fig. 6.3) (Simandi et al., 1997). 

The initial objective of the approach was cobyric acid (334), in which the propionic substituent at the 17-position must be differentiated from all other amides in the molecule ... 

The reaction of CO2 fixation onto phosphoenolpyruvic acid by PEP carboxytransphosphorylase is considered (O Brien and Wood, 1974) as a control mechanism of propionic acid fermentation. They observed a conversion of the enzymatically active tetrameric form of PEP carboxytransphosphorylase isolated from P. shermanii into a less active dimeric form induced by oxalate, malate and fumarate. Therefore, the loss of activity by enzyme dissociation, accompanied by increased proteolysis, is an effective means of controlling the level of intermediates in propionic acid fermentation. Differential abilities of propionibacteria to fix CO2 could be associated (Wood and Leaver, 1953) with their abilities to carry out the reaction C02 Ci and to form sulfhydryl complexes with Ci. 

Although fermentation of fiber tends to reduce its effectiveness as a source of fecal bulk, it has other very important benefits. The absorption and metabolism of short-chain fatty acids derived from carbohydrate fermentation provides the route for the recovery of energy from undigested polysaccharides. Butyrate functions as the preferred source of energy for the colonic mucosal cells, whilst propionate and acetate are absorbed and metabolized systemically. There continues to be much debate about the importance of butyrate for the colon. In vitro, butyrate causes differentiation of tumor cells, suppresses cell division, and induces programed cell death (apoptosis). These effects are thought likely to suppress the development of cancer, but it is not yet entirely clear whether they also occur in the intact intestine. Research continues on the importance of butyrate and other short-chain fatty acids for human health. 

The basic construction of the mathematical model using simplified metabolic networks to describe the reactions of the citric acid cycle and associated transamination reactions between pyruvate and alanine, oxalacetate and aspartate and a-ketoglutarate and glutamate, and the use of the FACSIMILE program (Chance et al., 1977) to solve the rather large number of simultaneous differential equations generated by the model was the same as previously described (Chance etal., 1983). For the present experiments the model was expanded to include an input flux at the level of succinate to represent propionate metabolism to succinyl-CoA, and a dilution of the aspartate pool to represent net proteolysis. These input fluxes required an output flux of carbon from the citric acid cycle in order to maintain a steady state carbon balance, for which the conversion of malate to pyruvate via malic enzyme was chosen. The model calculates the unknown flux parameters to provide a minimum least squares fit of the C fractional enrichments of specific carbon atoms of metabolic intermediates as measured by C NMR spectroscopy. 

Note that MS/MS is unable to distinguish between isomeric acylcarnitines. Therefore, elevations of C4 can be either from accumulation of butyr-yl or isobutyryl carnitine, C5 can be either isovaleryl or 2-methylbutyryl and so on. Some individual metabolites are characteristic of more that one disease. Propionylcarnitine is markedly elevated in both propionic and methylmalonic acidemia. 3-Hydroxyisovalerylcarnitine (OH-C5) is associated with both 3-MCC deficiency and HMG-CoA-lyase deficiency. Minor elevations in either or both of these metabolites are also consistent with ho-locarboxylase deficiency or with deficiency of the cofactor biotin (or bioti-nidase). The differential diagnosis of each of these conditions is generally made from a careful analysis of urinary organic acids, performed by capillary column GC/MS in a reputable facility. This is especially important in the follow-up of abnormal newborn screening acylcarnitine results. 

Another feature of the cobyric acid molecule is that it contains all the peripheral carboxy functions in the primary amide form, except for the propionate chain on ring D. Therefore, the problem of differentiating one chain terminus from all the others adorning the corrin nucleus is quite crucial, and has been solved by masking the ring D carboxy function as a nitrile until the penultimate Step. 

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