Biosynthesis of phosphatidylinositol in rat brain

Thompson, W.; Strickland, K. P.; Rossiter, R. J.

doi:10.1042/bj0870136

Cited by 63 publications

(18 citation statements)

References 23 publications

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“…Previous work in this laboratory and elsewhere has shown that various mammalian systems, including isolated oligodendroglia, are capable of incorporating rityo-inositol into phosphatidylinositol by two routes, which can be distinguished by their cytidine nucleotide and divalent cation requirements (Agranoff et al, 1958;Paulus and Kennedy, 1960; Thompson et al, 1963;Takenawa et al, 1977;Yandrasitz and Segal, 1979;Brammer and Carey, 1980). In the present investigation, we have shown that in oligodendroglia, as in other cell types, the CTP-dependent pathway of inositol incorporation can operate with either Mn2+ or Mgz+ as the divalent cation cofactor.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Divalent Cations and Substrate Concentration on the Incorporation of Myo‐inositol into Phospholipids of Isolated Bovine Oligodendrocytes

Gibson¹,

Brammer²

1981

Journal of Neurochemistry

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The incorporation of myo-inositol into phosphatidylinositol by two routes (CTP-independent and CTP-independent) has been investigated in homogenates prepared from isolated bovine oligodendrocyte perikarya. The CTP-dependent route has the higher maximum velocity of inositol incorporation and can utilise either Mn2+ or Mg2+ as a divalent ion cofactor. This route of inositol incorporation is also strongly inhibited by Ca2+ ions at concentrations less than 1 mM. The primary site of the inhibitory action appears to be the enzyme CDP-diglyceride inositol phosphatidyl transferase (EC 2.7.8.11) though synthesis of CDP-diacylglycerol is also inhibited by endogenous Ca2+ present in the oligodendrocyte homogenate. In contrast, CTP-independent inositol incorporation into phosphatidylinositol is only stimulated by Mn2+ (Zn2+,Cu2+, Mg2+, Ca2+ and Co2+ are ineffective) and is not inhibited by Ca2+, at least up to a concentration of 1 mM.

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Section: Discussionmentioning

confidence: 99%

The Influence of Divalent Cations and Substrate Concentration on the Incorporation of Myo‐inositol into Phospholipids of Isolated Bovine Oligodendrocytes

Gibson¹,

Brammer²

1981

Journal of Neurochemistry

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“…There have been a number of reports in the literature (1,2,5) indicating that added CTP and CDP-choline can greatly stimulate the entry of free inositol into PI, even though phosphatidate is omitted, when microsomes from various tissues are incubated in the presence of divalent cations such as Mn 2+ or Mg 2+. It has been speculated that these effects of nucleotide coenzymes may reflect the de novo synthesis of PI from endogenous CDP-diglyceride, which, in turn, could be derived from endogenous phosphatidic acid (5), or from an enhancement of a microsomal exchange reaction between free inositol and inositol in phospholipid, which would not provide for the net synthesis of PI (1).…”

Section: Discussionmentioning

confidence: 99%

“…CRelative specific activity is defined as the % of total radioactivity in the class, divided by the mole-% contribution of the class to the total mixture~ free inositol. Alternatively, it has been suggested that the nucleotides may stimulate inositol entry into microsomal PI by enhancing the exchange reaction (1,2). The purpose of the work described herein was to determine the likely mechanism by which cytidine nucleotides enhance the entry of inositol into PI in rat liver microsomes.…”

Section: Introductionmentioning

confidence: 99%

“…It is well established that free inositol can be incorporated into phosphatidylinositol either by reacting with cytidine diphosphate digtycerides (CDP-diglycerides) derived from cytidine triphosphate (CTP) and phosphatidic acid (1)(2)(3)(4)(5) or by a microsomal exchange reaction (1,6). The former pathway provides for the de novo biosynthesis of phosphatidylinositol (PI), while the latter pathway would give rise to no net synthesis of this phospholipid if microsomal PI was the endogenous substrate, as has been suggested (1).…”

Section: Introductionmentioning

confidence: 99%

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Role of cytidine triphosphate and cytidine diphosphate in promoting inositol entry into microsomal phosphatidylinositol

Holub

1975

Lipids

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The Mn2+ activated incorporation of myo-inositol-3H into subfractions of phosphatidylinositol in rat liver microsomes was studied in the presence and absence of cytidine triphosphate or cytidine diphosphate choline using phosphate buffer. The distribution of labeled inositol among molecular species of microsomal phosphatidylinositol was also investigated in vivo. In other experiments, the release of radioactivity from microsomes labeled with inositol-3H in the phospholipid was measured after the addition of Mn2+, unlabeled inositol, and cytidine nucleotide. Similar chase experiments were conducted with microsomes containing phosphatidylcholine-14C or phosphatidylethanolamine-14C. The addition of cytidine triphosphate or cytidine diphosphate choline stimulated the rate of inositol-3H entry into microsomal phosphatidylinositol by 3.5 to 4-fold and the monoenoic plus dienoic, trienoic, tetraenoic, and polyenoic species contained 6-7, 6, 78-81, and 7-9%, of radioactivity, respectively. These latter patterns were very similar to those observed among the corresponding molecular species when the Mn2+ stimulated entry of free inositol into phospholipid was studied in the absence of added cytidine nucleotide. In chase experiments, the release of radioactivity from phospholipid in the presence of cytidine trephosphate or cytidine diphosphate choline was greatly enhanced by the addition of free inositol when microsomes containing phosphatidylinositol-3H, but not phosphatidylcholine-14C or phosphatidylethanolamine-14C, were employed. Therefore, under the present conditions, cytidine triphosphate and cytidine diphosphate choline appear to stimulate the entry of inositol into phosphatidylinositol by enhancing the Mn2+ activated exchange reaction in rat liver microsomes. The results suggest further that phosphatidylinositol is the preferred substrate when this reaction is stimulated by cytidine nucleotide.

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“…It is assumed that the diglyceride moiety is stable and is bound to the membrane throughout the sequence. Reactions 3 and 4 are the generally accepted pathways for the synthesis of phosphatidylinositol (13,22). Reaction 2 is one of the three alternative pathways known for the synthesis of phosphatidic acid in brain (23).…”

Section: Hypothetical Reaction Sequencementioning

confidence: 99%