Enzymes epimers

Enzyme-substrate complex (Section 24.9) The species formed when a substrate (reactant) binds at the active site of an enzyme. Epimers, epimerization (Sections 18.3A and 22.8) Diastereomers that differ in configuration at only a single tetrahedral chirality center. Epimerization is the interconversion of epimers. 

Enzyme-substrate complex, 1041 Ephedrine, structure of, 65 Epibatidine, molecular model of. 332 Epichlorohydrin, epoxy resins from, 673-674 Epimer, 303... 

Other enzyme-based mechanisms. Furthermore, the epimers of artemether showed nearly equal in vivo activity (1.02 mg/kg of body weight for a epimer versus 1.42 mg/kg of body weight for the P epimer), making the heme-based mechanism preferable over the SERCA-based mechanism for which a greater disparity in the activities would be expected. Whatever the situation may be, we all agree that further studies are necessary to clarify, or to unambiguously determine the real mechanism of action of this family of compounds. 

The next area for study was the pathway between strictosidine (33) and cathenamine (76), where the initial step is viewed as hydrolysis by p-glucosidase and opening of the hemiacetal to a dialdehyde 93. Attempts to trap this intermediate 200) have thus far failed, and it appears that recyclization and dehydration occur too rapidly, giving rise to 4,21-dehy-drocorynantheine aldehyde (94). Thus, an enzyme preparation was incubated at pH 7.0 in the presence of KBH4 to afford the C-16 epimers 69 and 95, thereby impuning the existence of 94. 

RIBULOSE-5-PHOSPHATE 3-EPIM ERASE Escherichia coll glutamine synthetase, ENZYME CASCADE KINETICS GLUTAMINE SYNTHETASE Essential amino acid residues in catalysis, AFFINITY LABELING ESTERASES... 

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

By reversing the ratio of acceptor/donor, namely by using D-arabinose in a 25-fold excess, the percentage of KDO, the product of the inverted enzyme stereoselectivity, could be increased up to 83% [48]. The reason for that is still unclear, but this interesting result was exploited in the preparation of KDO 2, which was achieved using the enzyme membrane reactor technique [48]. Compound 2 could be separated from its epimer according to the procedure previously described [16]. 

The attached polymers undergo enzyme-catalyzed chemical alteration. In dermatan most of the glucu-ronate residues found in chondroitin have been epimer-ized to iduronate and sulfate groups in ester linkages have been added. Chondroitin sulfate is especially abundant in cartilage dermatan sulfate is concentrated in skin. Heparan sulfates are more heterogeneous than the other polymers of this group and have been described as "the most complex polysaccharides on the surface of mammalian cells."110... 

UDP-Gal 4-epimerase16 161 (Eq. 20-1, step c see also Eq. 15-13 and accompanying discussion). Absence of this enzyme also causes galactosemia.11 The overall effect of the reactions of Eq. 20-1 is to transform galactose into glucose 1 -P. At the same time, the 4-epimer-ase can operate in the reverse direction to convert UDP-glucose to UDP-galactose, when the latter is needed for biosynthesis (Fig. 20-1). 

The 5-epi-aristoIochene synthase of tobacco makes the 5-epimer of aristolochene (Fig. 22-4). It binds the diphosphate group within a central cavity using two Mg2+ ions held by carboxylates, some of which are in the DDXXD sequence found also in polyprenyl diphosphate synthases. The enzyme active sites of both the epi-aristolochene synthase and a pentale-nene synthase from Streptomyces96 are rich in polar groups that form hydrogen-bonded networks and which participate in proton abstraction and donation during the rearrangement reactions that must occur. 

Nevertheless, there are many questions still open because of problems to detect enzyme activities corresponding to each step of the pathway. The model of biosynthesis pathway was put together by studying the metabolism of exogenously applied intermediates in cell cultures of various origins and combining these results with data of native brassinosteroid patterns. It is more or less accepted that there are three pathways in parallel, the early and the late C6 oxidation pathway, as well as the 24/ -epimers follow ing the same route. Some observations in the analysis of native brassinosteroid patterns suggest a possible connection between the pathways. It was shown that seeds of Arabidopsis contain castasterone and 24-epi-brassinolide [34]. Also members of both 24-epimers, brassinolide and 24-epi-brassinolide were detected in tomato seeds [Winter, unpublished]. 

Experimental evidence for activated forms of the sugars of this group is presented only in the case of 6-deoxytalose, which is an epimer, at C-4, of 6-deoxymannose. In the d series, the GDP derivative of the monosaccharide is formed, together with GDP-D-rhamnose, through nonspecific, enzymic... 

Hexokinase will also phosphorylate D-fructose(IX) and fructose analogs. This shows that the enzyme also will accept furanose rings at the active site. The same hydroxyls appear to be important for binding and activity since d-tagatose(X) and D-psicose(XI), the C-4 and C-3 epimers of fructose, are not substrates for hexokinase (37). 

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