Ethanolamine choline from

The anaemia in B deficiency is caused by an inability to produce sufficient of the methylating agent S-adenosyhnethionine. This is required by proliferating cells for methyl group transfer, needed for synthesis of the deoxythymidine nucleotide for DNA synthesis (see below and Chapter 20). This leads to failure of the development of the nucleus in the precursor cells for erythrocytes. The neuropathy, which affects peripheral nerves as well as those in the brain, is probably due to lack of methionine for methyl transfer to form choline from ethanolamine, which is required for synthesis of phosphoglycerides and sphingomyelin which are required for formation of myelin and cell membranes. Hence, the neuropathy results from a... 

Formation of ethanolamine from betaine and of choline from ethanolamine was also shown by the experiments of Stetten. The data are reproduced in Table I. The observations support the main features of the cycle represented in Fig. 1, namely that ethanolamine is formed by the decarboxylation of serine, this in turn is methylated to choline, which is then oxidized to betaine, and the latter is demethylated to glycine. Further support for this scheme is supplied by the observations of Arn-stein that L-serine-S-C is converted to choline with about the same degree of efficiency as N -glycine and that glycine-l-C is not a precursor of choline. 

Ethanolamine cephalins are formed in the same way, i.e. ethanolamine is activated with CDP and transferred onto a diglyceride. Cephalins may be methylated to produce lecithins with adenosylmethionine as methyl group donor. This methyla-tion apparently is the main biosynthetic pathway of lecithin and is an important source of choline from ethanolamine (Greenberg and Bremer). 

Folic acid (pteroyhnonoglutamic acid or PGA) exists in different forms in nature. These forms are changed to at least five active coenzymes critically important for the formation of purines and pyrimidines needed for the synthesis of DNA and RNA, the formation of hanoglobin, the interconversion of amino acids such as homocysteine to methionine, and the synthesis of choline from ethanolamine. Vitamins B,2, Bg, and C are essential as coenzymes for the activity of folacin in many metabolic processes. In practical terms, folic acid is required for cell division and reproduction, and prevents neural tube defects in newborns and cardiovascular diseases in adults. The cardiovascular protective role is because folacin and vitamin Bjj lower levels of homocysteine. 

Lecithin. Lecithin [8002-43-5] (qv) is a mixture of fat-like compounds that includes phosphatidyl choline, phosphatidyl ethanolamines, inositol phosphatides, and other compounds (37). Commercial lecithin was originally obtained from egg yolks, but is now extracted from soybean oil. Lecithin is used in many products, including margarine, chocolate, ice cream, cake batter, and bread. 

Figure 24-2. Biosynthesis of triaq/lglycerol and phospholipids. ( , Monoacylglycerol pathway (D, glycerol phosphate pathway.) Phosphatidylethanolamine may be formed from ethanolamine by a pathway similar to that shown for the formation of phosphatidylcholine from choline.

Figure 3.2 The molecular arrangement of the cell membrane (A) integral proteins (B) glycoprotein (C) pore formed from integral protein (D) various phospholipids with saturated fatty acid chains (E) phospholipids with unsaturated fatty acid chains (F) network proteins (G) cholesterol (H) glycolipid (I) peripheral protein. There are four different phospholipids phosphatidyl serine phosphatidyl choline phosphatidyl ethanolamine and sphingomyelin represented as , o. The stippled area of the protein represents the hydrophobic portion. Source From Ref. 1.

Mammalian cells have some pathways similar to those in bacteria, but somewhat different routes for synthesizing phosphatidylcholine and phosphatidylethanolamine. The head-group alcohol (choline or ethanolamine) is activated as the CDP derivative, then condensed with diacylglycerol. Phosphatidylserine is derived only from phosphatidylethanolamine. 

PC and PE are the most abundant phospholipids in most eukaryotic cells. The primary route of their synthesis uses choline and ethanolamine obtained either from the diet or from the turnover of the body s phospholipids. [Note In the liver, PC also can be synthesized from phosphatidylserine (PS) and PE (see below).]... 

Synthesis of PE and PC from preexisting choline and ethanolamine These synthetic pathways involve the phosphorylation of choline or ethanolamine by kinases, followed by conversion to the activated form, CDP-choline or CDP-ethanolamine. Finally, choline-phosphate or ethanolamine-phosphate is transferred from the nucleotide (leaving CMP) to a molecule of diacylglycerol (see Figure 17.5). 

Cho et al. (1977) has identified the fatty acids in the lysophosphati-dyl-ethanolamines and -cholines from butter serum. The compositions were similar to those of the intact phospholipids. 

Choline and ethanolamine are activated in much the same way as are sugars. For example, choline can be phosphorylated using ATP (Eq. 17-58, step a) and the phosphocholine formed can be further converted (Eq. 17-58, step b) to cytidine diphosphate choline. Phosphocholine is transferred from the latter onto a suitable acceptor to form the final product (Eq. 17-58, step c). Tire polymerization pattern differs from that for polysaccharide synthesis. When the sugar nucleotides react, the entire nucleoside diphosphate is eliminated (Eq. 17-56), but CDP-choline and CDP-ethanolamine react with elimination of CMP (Eq. 

It is postulated that inhibition of PtdCho synthesis and the release of choline are key steps associated with excitotoxicity and are common to NMDA and AMPA receptor stimulation. The mechanism of inhibition of PtdCho is not fully understood. Metabolic labeling experiments in cortical cultures demonstrate that NMDA receptor over activation does not modify the activity of phosphochohne or phospho-ethanolamine cytidylyltransferases but strongly inhibits choline and ethanolamine phosphotransferase activities. This effect is observed well before any significant membrane damage and cell death. Moreover, cholinephosphotransferase activity is lower in microsomes from NMDA-treated cells. These results show that membrane... 

In mammals, a pathway that utilizes choline obtained from the diet ends in the synthesis of phosphatidyl choline, the most common phospholipid in these organisms. In this case, choline is activated in a series of reactions analogous to those in the activation of ethanolamine. Interestingly, the liver possesses an enzyme, phosphatidyl ethanolamine methyltransferase, that synthesizes phosphatidyl choline from phosphatidyl ethanolamine, through the successive... 

Neuronal systems using acetylcholine as a neurotransinitter have been among those more widely studied. Acetylcholine was the first neurotransmitter isolated by scientists. The precursor of this neurotransmitter is choline, which is derived either from dietary lecithin or from intracellular metabolism. Choline can be formed from ethanolamine, the decarboxylated product of serine, via a complex series of reactions. The relative normal contributions of endogenous or exogenous choline to the precursor pool is not established. It is known that choline loading can substantially enhance the level of choline within the brain. 

Lecithin, a mixture of phosphatidyl choline, phosphaddyl ethanolamine, and phosphatidyl inositol, is used as a surfactant in many food, pharmaceutical, and cosmetic products. Lecithin is a product of soy bean oil degumming operations. It is obtained from the hexane extract of flaked soy beans which contains the seed oil and a portion of the phosphatides that are initially present in the soy bean membrane. The exhact is seated with water at 80 °C, and the phosphatides are hydrated rendering them oil insoluble which makes it easy to filler them from the oil. This oil insoluble fraction is termed cmde lecithin and consists of about 70% phosphatides and 30% oil. De-oiled lecithin is obtained by treating the cmde lecithin with acetone. Lecithin is insoluble in acetone and the oil is, and a separation into a 90 to 9r phosphatides fraction can be achieved quite readily. The prior... 

Defatting. When tofu, a protein curd made from whole soybean, was treated with Molsin, in addition to volatile compounds, nonvolatile fatty materials were liberated including triglygerides, fatty acids, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, sito-steryl-D-glucoside, genistein, saponins, etc. (84). 

Fig. 21-5, are also used for formation of both phosphatidylcholine and phosphatidylethanolamine. In both cases, the free base, choline, or ethanolamine is phosphorylated with ATP. Choline phosphate formed in this manner is then converted by reaction with CTP to CDP-choline (Eq. 17-58). Phosphatidylcholine is formed from this intermediate while CDP-ethanolamine is used to form phosphatidylethanolamine (Fig. 21-5). These S5mthetic reactions occur within cell nuclei as well as on surfaces of cytoplasmic membranes. ...

Shelley, R.M. Hodgson, E. Substrate specificity and inhibition of choline and ethanolamine kinases from the fat body of Phormina regina larvae. Insect Biochem., 1, 149-156 (1971)... 

If depressants inhibit the utilization of energy-rich phosphates, phospholipid biosynthesis might be expected to be affected. With a dose of 60 mg/kg body weight of thiopentone [5-ethyl-5-(l-methylbutyl)-2-thio-barbitone], Dawson and Richter (1950b) convincingly demonstrated a reduction in the rate of transfer of labeled phosphate from the water-soluble pool to the phospholipids of mouse brain. This was not due to the hypothermia induced by the anesthetic. Ansell and Dohmen (1957) confirmed this for a number of phospholipids, including phosphatidylcholine and -ethanolamine. It was subsequenUy shown that the phosphorylation of the bases choline and ethanolamine was unaffected (Ansell, 1960). This was presumably a consequence of the unchanged level of ATP. 

X 10— Stimulated incorporation of activity from Ci -labeled glycerol, glycine, and serine into phospholipids but had no effect on C -labeled choline and ethanolamine (Pritchard and Rossiter, 1963)... 

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