Base exchange enzyme

Buratta, S., Migliorati, G., Marchetti, C., Mambrini, R., Riccardi, C., and Mozzi, R., 2000, Dexamethasone increases the incorporation of [3H]serine into phosphatidylserine and the activity of serine base exchange enzyme in mouse thymocytes a possible relation between serine base exchange enzyme and apoptosis. MoZ. Cell. Biochem. 211 61-67. 

Phosphatidylserine biosynthesis in animals is catalyzed by a base exchange enzyme on the endoplasmic reticulum. Decarboxylation of phosphatidylserine occurs in mitochondria. The cyclic process of phosphatidylserine formation from phosphatidylethanolamine and the reformation of phosphatidylethanolamine by decarboxylation has the net effect of converting serine to ethanolamine. This is a major mechanism for the synthesis of ethanolamine in many eukaryotes. 

Biosynthesis of phosphatidylethanolamine from phosphatidylserine. The base-exchange enzyme on the cytosolic face of the endoplasmic reticulum can interconvert these phospholipids in the pre,sence of Ca and the alternate head group, serine or ethanolamine. The decarboxylase is localized in the inner membrane of mitochondria and catalyzes the nonequilibrium conversion of phosphatidylserine to phosphatidylethanolamine. 

Phosphatidylethanolamines can also be synthesized by decarboxylation of phosphatidylserine and in mammals principally through action of the Ca -mediated base exchange enzyme (Figure 19-3). Phosphatidylserine production in liver occurs at the cytosolic face of the endoplasmic reticulum. In brain tissue, this phospholipid accounts for up to 15% of the total phospholipid content. 

Fig. 7. Biosynthesis of choline plasmalogens (plasmenylcholines) via modification of the sn-3 polar head group of ethanolamine plasmalogens (plasmenylethanolamines). These reactions are proposed to be catalyzed directly by (1) a base exchange enzyme or (II) At-methyltransferase. A combination of other enzymatic reactions could also result in replacement of the ethanolamine moiety of plasmenylethanolamine to produce plasmenylcholines the enzymes responsible include (IB) phospholipase C, (IV) the reverse reaction of ethanolamine phosphotransferase, (V) phospholipase D, (VI) phosphohydtolase, and (VII) cholinephosphotransferase. AdoMet, 5-adenosyl-L-methionine AdoHcy, 5-adenosyl-L-homocysteine Etn, ethanolamine GPE, sn-glycero-...

Figure 2. Biosynthesis of plasmalogens in mammalian tissues. Enzymes (1) dihydroxyacetone phosphate acyltransferase (2) 1-acyldihydroxyacetone phosphate synthase (3) 1-alkyldihydroxyacetone phosphate oxidoreductase (4) l-alkyl-5n-glycero-3-phosphate acyltransferase (5) 1-afkyl 2-acyl-5w-glycero-3-phosphohydrolase (6) CDP-ethanolamine transferase (7) l-alkyl-2-acyl-5w-glycero-3-phosphoethanolamine desaturase (8) methyltransferases and base-exchange enzymes. CDP-ethanolamine, cytidine diphosphoethanolamine. CMP, cytidine monophosphate. CoA, coenzyme A. DHAP, dihydroxyacetone phosphate. NADH, nicotinamide adenine dinucleotide, reduced form. NAD, nicotinamide adenine dinucleotide, oxidized form. Pi, phosphate.

The enzyme has now been purified by Kanfer and, although it was first thought to be a phospholipase, the purified base-exchange enzyme had no such phospholipase activity. 

Sanders, B.D., Zhao, K., Slama, J.T and Marmorstein, R. (2007) Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes. Molecular Cell, 25 (3), 463 72. 

In prokaryotes, phosphatidylserine is made from CDP-diacylglycerol (see fig. 19.3). The enzyme for this reaction is absent in animal cells, which rely on a base exchange reaction in which serine and ethanolamine are interchanged (fig. 19.8). Although the reaction is reversible, it usually proceeds in the direction of phosphatidylserine synthesis. Phosphatidylserine can be converted back to phos-phatidylethanolamine by a decarboxylation reaction in the mitochondria. This may be the preferred route for phosphatidylethanolamine biosynthesis in some animal cells. Furthermore these two reactions (see fig. 19.8) establish a cycle that has the net effect of converting serine into ethanolamine. This is the main route for ethanolamine synthesis... 

Phosphatidylcholine is synthesized via the Kennedy pathway (Kennedy and Weiss, 1956) in three consecutive steps catalyzed by the enzymes choline kinase, phosphocholine cytidyltransferase, and phosphocholine transferase. Phospha-tidylethanolamine is synthesized via the corresponding pathway for ethanolamine or by decarboxylation of phosphatidylserine (Borkenhagen et al., 1961) or by base exchange (Bjerve, 1973). In immobilized breast cancer cells, flux in these pathways... 

In addition to its capability as a phosphodiesterase, this enzyme also was found by Yang et al. (1967) to possess transphosphatidylase activity (essentially a base exchange reaction) as illustrated in Figure 4-17. 

Introduction of a fluoride at the 3-position of neuraminic acid yielded a compound (57) that was a competitive inhibitor of the a-(2,6)-sialyl-trans-ferase. Base and sugar-modified analogues of CMP-Neu5Ac have also been prepared to investigate the tolerance of oc-(2,6)-sialyl-transferase to base exchange (58) and modification of the 5-, 8- or 9-position of neuraminic acid (59), (60). While base-exchange was not tolerated, modifications of the acid moiety yielded compounds that were substrates for the enzyme. 

Furthermore, some base exchanges result in so-called silent mutations which do not cause amino acid exchanges in the enzyme. In addition, nonsense codons also occur which usually result in termination of translation. 

All PLDs characterized thus far act by a phosphatidate exchange reaction that involves a covalent phosphatidyl-enzyme as an intermediate [33]. For this reason, PLD can catalyze a base-exchange reaction in which alcohols can substitute for water as the... 

The use of biological methods has a small but significant niche in synthetic heterocyclic chemistry, being used both on a research scale and for fine chemicals production. The processes may use isolated enzymes or whole microorganisms, the main reactions being oxidations of a heterocyclic nucleus or of side-chains. Some other reaction types are referred to later in the book, for example enzyme-catalysed base exchange in nucleosides and the deamination of adenosine. 

Mortland and Gieseking (1952) found that all the clays that they studied exerted an inhibiting effect upon the enzymatic hydrolysis of organic phosphorus c ompounds. The effect of the clays was as follows montmorillonite > Cisne > illite > kaolinite. The inhibition of phosphatase activity corresponded closely to the base exchange capacity of the clays, and was due primarily to their effect on the enzyme and riot to adsorption of the organic phosphorus compounds by the clays. 

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