Kennedy pathway

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.

The majority of PC is synthesized in mammalian cells by the CDP-choline or Kennedy pathway in the endoplasmic reticulum (Eigiue 1). In this pathway, choline taken up from the external medium or released in the cytosol by breakdown of choline containing compoimds, is first converted to phosphocholine by the enzyme choline kinase (CK) (Ishidate, 1997). There are two isoforms of CK cloned which both can convert also ethanolamine to phosphoethanolamine, albeit with a lesser affinity (Aoyama et al 2000). Alternatively phosphocholine can be generated by enzymes that preferentially phosphorylate ethanolamine and are therefore designated ethanolamine kinases (EK). As yet also two different EKs are known (EKI 1 and 2 Lykidis etal., 2001). 

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... 

E. coli possesses only three major phospholipid species in its membranes, making it one of the simplest organisms to study with regard to phospholipid biosynthesis. Phosphatidylethanolamine (PE) comprises the bulk of the phospholipids (75%), with PtdGro and Ptd2Gro forming the remainder (15-20% and 5-10%, respectively). The scheme for the synthesis of membrane phospholipids follows the classic Kennedy pathway (Fig. 6). 

Perry, H.J., R. Bligny, E. Gout, and J.L. Harwood. 1999. Changes in Kennedy pathway intermediates associated with increased triacylglycerol synthesis in oil-seed rape. Phytochemistry 52 799-804. 

Cloning and Characterization of Kennedy Pathway Acyltransferases from Novel Oilseed Species... 

Various Enzymes of the Kennedy Pathway and Land s Cycle May Be... 

Key Words Acyltransferase diacylglycerol glycerol-3-phosphate Kennedy pathway Land s cycle lysophosphatidic acid triacylglycerol. 

VARIOUS ENZYMES OF THE KENNEDY PATHWAY AND LAND S CYCLE MAY BE NECESSARY FOR EFFICIENT PACKAGING OF UNUSUAL FATTY ACIDS IN STORAGE LIPIDS... 

As stated, the inability of individual biosynthetic enzymes to produce levels of novel fatty acids comparable to that of their native species indicates that one or more enzymes of Land s cycle or Kennedy pathway may have coevolved to aid in the... 

The analysis of plant DGATs, especially the DGAT2 class, has certainly provided powerful tools for the manipulation of seed oil fatty acid content. However, the results from the FAHllIRcDGATl coexpression experiments suggest that even more enzymes of the Land s cycle and Kennedy pathway must be included to achieve industrially meaningful levels of novel fatty acids. The task of identifying which relevant genes to pursue is complicated by several factors ... 

Synthesis of polar and non-polar lipids in plants as well as animals is via the glycerol phosphate or Kennedy pathway (5). In this pathway 3-sn-glycerol phosphate, formed by reduction of dihydroxyacetone phpsphqte, is, acy.late(L by. acyl CoA in the 1- and... 

Figure 4. Acyl CoA dependent pathway of TAG biosynthesis (Kennedy pathway) [69],...

Rather similar data are shown in Table 2, which refers to displacement experiments carried out on microsomal Ptd-Cho pre-label-led Xn )Xi/lo from CDP-choline through the Kennedy pathway. Indeed, after 9 min of incubation, L-serine and ethanolamine displace the lipid-choline moiety by only 6% and 4%, respectively, and choline by only 2%. These data differ essentially from those described in Fig. 2, which reported the percentages of displacement rates of lipid-choline pre-labelled by base-exchange, and which... 

Arvidson (1968b) has shown in rat liver the presence of PCg with different metabolic stability demonstrating that the dienoic, and to a lesser degree the monoenoic species, incorporated radioactive choline and lost the label very rapidly, while tetraenoic PCg showed a slow and smaller incorporation. The explanation given by this investigator as well as by Van Golde et al. (1969) and by Kanoh (1969) was that the mono-dienoic fraction was synthesized de novo through the Kennedy pathway while the tetraenoic derivatives were synthesized by re-acylation of lysophosphatidyl choline. Recent studies by Parkes... 

Triacylglycerols are assembled by the enzymes of the Kennedy pathway [6] which are located in the endoplasmic reticulum the sequence of enzymatic reactions involved is shown in the following scheme [7]. 

The acyl pattern of the final mixture of triacylglycerols is characteristic for each seed oil. The specific acyl chain targeting depends on both the selectivity of the various acyltransferases (AT 1, acyl-CoA sn-glycerol-3-phosphate acyl-transferase, E.C. 2.3.1.15 AT 2, acyl-CoA l-acyl-j -glycero-3-phosphate acyl-transferase, E.C.2.3.1.51 ATS, acyl-CoA l,2-diacyl-5n-glycerol acyltransferase, E.C. 2.3.1.20) of the Kennedy pathway and the compartmentation of triacylglycerol biosynthesis and/or acyl chain modification [6, 8],... 

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