Serine decarboxylase

Although phosphatidylserine is in general asymmetrically distributed in cell membranes with the bulk of this lipid in the cytoplasmic leaflet of the bilayer, some phosphatidylserine appears to reside in the outer lipid monolayer of the axonal membrane. Furthermore, this phosphatidylserine is involved in the nerve action potential. Treatment of an axon with extracellular serine decarboxylase converts phosphatidylserine to -ethanolamine, which results in a decrease in the action potential spike height. Catalysis of the reversed reaction by this enzyme in the presence of excess L-serine converts phosphatidylethanolamine to -serine. This produces an average of 28% increase in the action potential amplitude. It is worth noticing that several anaesthetic compounds have been shown to bind phosphatidylserine in vitroThe role of phosphatidylserine phase behavior in the nerve action potential will be discussed in somewhat more detail in Section 7. 

The magnitude of the conversion of serine to ethanolamine appears to be quite high. This is extremely interesting in view of the fact that it has not been possible to demonstrate the presem e of an active serine decarboxylase in mammalian tissues. In the experiment of Stetten, 2.6% of the ethanolamine in the phosphatides of the liver of his animals was formed from the isotopic serine in eight days. Since the serine in the phosphatides showed a 6 % incorporation of the label, he reasoned that if the serine decarboxylated had the same isotopic concentration, the actual ethanolamine synthesized was 100(2.6/6.0), or 43% of the total phosphatide ethanolamine. This figure probably is high, as the dilution would not be expected to be complete throughout the decarboxylation process. 

Mammals synthesize phosphatidylserine (PS) in a calcium ion-dependent reaction involving aminoalcohol exchange (Figure 25.21). The enzyme catalyzing this reaction is associated with the endoplasmic reticulum and will accept phosphatidylethanolamine (PE) and other phospholipid substrates. A mitochondrial PS decarboxylase can subsequently convert PS to PE. No other pathway converting serine to ethanolamine has been found. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Rat liver aminomalonate decarboxylase has recently been identified with cytoplasmic serine hydroxymethylase and allothreonine aldolase 17>. Most references in this narrative have been omitted, since they can all be found in Popjack s review t). 

Palekar, A. G., Tate, S. S., Meister, A. Rat liver aminomalonate decarboxylase. Identity with cytoplasmic serine hydroxymethylase and allothreonine aldolase. J. Biol. Chem. 248, 1158-1167 (1973). 

PDH is a multi-enzyme complex consisting of three separate enzyme units pyruvate decarboxylase, transacetylase and dihydrolipoyl dehydrogenase. Serine residues within the decarboxylase subunit are the target for a kinase which causes inhibition of the PDH the inhibition can be rescued by a phosphatase. The PDH kinase (PDH-K) is itself activated, and the phosphatase reciprocally inhibited, by NADH and acetyl-CoA. Figure 3.12(a and b) show the role and control of PDH. 

Control of pymvate dehydrogenase activity is via covalent modification a specific kinase causes inactivation of the PDH by phosphorylation of three serine residues located in the pyruvate decarboxylase/dehydrogenase component whilst a phosphatase activates PDH by removing the phosphates. The kinase and phosphatase enzymes are non-covalently associated with the transacetylase unit of the complex. Here again we have an example of simultaneous but opposite control of enzyme activity, that is, reciprocal regulation. 

Figure 1. Synthetic pathway for PS and PE in mammalian cells. The major steps occuring in the synthesis and interconversion of PS and PE are shown. The PS synthases condense serine with a phosphatidyl moiety derived from PC and PE. The nascent PS can be converted to PE by decarboxylation. PE can also be formed by transfer of a phosphoethanolamine moiety from CDP-ethanolamine to diacylglycerol via the Kennedy pathway. The abbreviations used are PC, phosphatidylcholine PS, phosphatidylserine PE, phosphatidylethanolamine DG, diacylglycerol PSD, phosphatidylserine decarboxylase PSS, PS synthase.

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

The enzymatic reaction was performed at 30 °C for 2 hours in a volume of 1 ml of 250 mM phosphate buffer (pH 6.5) containing 50 mM of KOH, 32 U/ml of the enzyme, and [1- C]-substrate. The product was isolated as the methyl ester. When the (S)-enantiomer was employed as the substrate, C remained completely in the product, as confirmed by C NMR and HRMS. In addition, spin-spin coupling between and was observed in the product, and the frequency of the C-O bond-stretching vibration was down-shifted to 1690 cm" (cf. 1740 cm for C-O). On the contrary, reaction of the (R)-enantiomer resulted in the formation of (R)-monoacid containing C only within natural abundance. These results clearly indicate that the pro-R carboxyl group of malonic acid is ehminated to form (R)-phenylpropionate with inversion of configuration [28]. This is in sharp contrast to the known decarboxylation reaction by malonyl CoA decarboxylase [1] and serine hydroxymethyl transferase [2], which proceeds with retention of configuration. 

PLP-dependent enzymes catalyze the following types of reactions (1) loss of the ce-hydrogen as a proton, resulting in racemization (example alanine racemase), cyclization (example aminocyclopropane carboxylate synthase), or j8-elimation/replacement (example serine dehydratase) (2) loss of the a-carboxylate as carbon dioxide (example glutamate decarboxylase) (3) removal/replacement of a group by aldol cleavage (example threonine aldolase and (4) action via ketimine intermediates (example selenocysteine lyase). 

Non-pyridoxal Phosphate Dependent. Figure 2 depicts the postulated mechanism for a non-pyridoxal phosphate catal) zed decarboxylation of histidine to histamine involving a pyruvoyl residue instead of pyridoxal -5 - phosphate (20). Histidine decarboxylases from Lactobacillus 30a and a Micrococcus sp. have been shown to contain a covalently bound pyruvoyl residue on the active site. The pyruvoyl group is covalently bound to the amino group of a phenylalanine residue on the enzyme, and is derived from a serine residue (21) of an inactive proenzyme (22). The pyruvoyl residue acts in a manner similar to pyridoxal phosphate in the decarboxylation reaction. 

Rebeille, F.,Neuburger,M., Douce, R. (1994). Interaction between glycine decarboxylase, serine hydroxymethyl-transferase and tetrahydrofolate polyglutamates in pea leaf mitochondria. Biochem. J., 302,223-228. 

Phosphatidylserine and phosphatidylglycerol can serve as precursors of other membrane lipids in bacteria (Fig. 21-25). Decarboxylation of the serine moiety in phosphatidylserine, catalyzed by phosphatidylserine decarboxylase, yields phosphatidylethanolamine. In E. coli, condensation of two molecules of phosphatidylglycerol, with elimination of one glycerol, yields... 

Yeast, like bacteria, can produce phosphatidylserine by condensation of CDP-diacylglycerol and serine, and can synthesize phosphatidylethanolamine from phosphatidylserine in the reaction catalyzed by phosphatidylserine decarboxylase (Fig. 21-27). In mammalian ceils, an alternative route to phosphatidylserine is a head-group... 

Beta-chloroalanine and serine O-sulfate can undergo (3 elimination (as in Eq. 14-29) in active sites of glutamate decarboxylase or aspartate aminotransferase. The enzymes then form free aminoacrylate, a reactive molecule that can undergo an aldol-type condensation with the external aldimine to give the following product.1... 

When 14C-labeled serine was fed to organisms producing histidine decarboxylase, 14C was incorporated into the bound pyruvoyl group (Fig. 14-11). Thus, serine is a precursor of the bound pyruvate. The enzyme is manufactured in the cell as a longer 307-residue proenzyme which associates as hexamers (designated n6). The active enzyme was found to be formed by cleavage of the n chains between Ser 81 and Ser 82 to form 226-residue a chains and 81-residue (3 chains which associate as (aP)6.270/271 The a chains... 

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