The phosphatidylinositol kinase of rat brain

Kai, Masahiro; White, G L; Hawthorne, J. N.

doi:10.1042/bj1010328

Cited by 135 publications

(62 citation statements)

References 20 publications

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“…This was obtained with diphosphoinositide in the preparation described above. It appeared pure by chromatography on formaldehyde-treated paper (Kai et al 1966b).…”

Section: Methodsmentioning

confidence: 99%

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The diphosphoinositide kinase of rat brain

Kai

Salway

Hawthorne

1968

Biochemical Journal

128

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1. The supernatant fraction of adult rat brain contains a diphosphoinositide kinase. 2. Formation of triphosphoinositide by the enzyme in the presence of ATP and Mg2+ ions was shown with labelled ATP or labelled diphosphoinositide. 3. The kinase was also activated by Ca2+, Mn2+ and Co2+ ions, but to a smaller extent than by Mg2+ ions. 4. In the presence of optimum Mg2+ ion concentration the enzyme was inhibited by Ca2+ ions. 5. Activity did not depend on thiol groups and the pH optimum was 7·3. 6. The dialysed supernatant fraction had no diglyceride kinase activity and negligible phosphatidylinositol kinase activity. 7. Triphosphoinositide phosphomonoesterase was present but showed little activity under the conditions used to assay the kinase. 8. Diphosphoinositide kinase was purified by ammonium sulphate fractionation, ethanol treatment and chromatography on Sephadex G-200. 9. This purification removed much of the triphosphoinositide phosphomonoesterase.

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“…This was obtained with diphosphoinositide in the preparation described above. It appeared pure by chromatography on formaldehyde-treated paper (Kai et al 1966b).…”

Section: Methodsmentioning

confidence: 99%

“…The first kinase involved, which produces diphosphoinositide, has been studied by Colodzin & Kennedy (1965), Michell & Hawthorne (1965) and Kai, White & Hawthorne (1966b). The second kinase, which forms triphosphoinositide from diphosphoinositide, was first studied by Kai, Salway, Michell & Hawthorne (1966a).…”

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confidence: 99%

The diphosphoinositide kinase of rat brain

Kai

Salway

Hawthorne

1968

Biochemical Journal

128

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“…PI is synthesized in brain from a liponucleoiide intermediate, cytidine diphosphodiacylglycerol (CDP-DG) (Agranoff et al, 1958), and inositol in the pres- ence of a transferase (Benjamins and Agranoff, 1969) and can then be phosphorylated via PI kinase and ATP to form phosphatidylinositol4-phosphate (PIP) (Colodzin and Kennedy, 1965;Kai et al, 1966). This product may be further phosphorylated via PIP kinase and ATP to form phosphatidylinositol 4,5-bisphosphate (PIP2) (Kai et al, 1968).…”

Section: Chemistry and Enzymology Of Inositol Lipids And Inositol Phomentioning

confidence: 99%

“…The abbreviations used for inositol lipids and inositol phosphates are those recommended at the Chilton Conference on Inositol and Phosphoinositides (Dallas, TX, January 1984) (see Agranoff et al, 1985). The standard IUPAC-IUB abbreviations for phosphatidylinositol, phosphatidylinositol4-phosphate, arid phosphatidylinositol 4,s-bisphosphate are PtdIns, PtdIns 4-P, and Pt- ence of a transferase (Benjamins and Agranoff, 1969) and can then be phosphorylated via PI kinase and ATP to form phosphatidylinositol4-phosphate (PIP) (Colodzin and Kennedy, 1965;Kai et al, 1966). This product may be further phosphorylated via PIP kinase and ATP to form phosphatidylinositol 4,5-bisphosphate (PIP2) (Kai et al, 1968).…”

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Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Fisher

Agranoff

1987

Journal of Neurochemistry

331

109

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Recent advances in our knowledge of the biochemistry, pharmacology, and cell biology of ligand-induced, stimulated turnover of inositol lipids in such diverse tissues as insect salivary glands, platelets, lymphocytes, and a number of exocrine glands have greatly altered our understanding of intracellular events leading to secretion, contraction, chemotaxis, and other cellular responses. Much of what has been learned regarding ligand-stimulated turnover of inosito1 lipids has come from nonneural systems, so that the presumption that signal transduction via this mechanism mediates significant steps in neural function must still be considered inferential. This reservation has been a major theme of a recent comprehensive review (Hawthorne, 1986). Nevertheless, that the brain contains large amounts of the substrates and enzymes of inositol lipid turnover and its associated second messenger systems and, further, that it is enriched with receptors that are linked to stimulated inositol lipid turnover argue strongly that the phosphoinositides indeed play an important role in brain function. There exist several general reviews on stimulated inositol lipid turnover (Bemidge, 1984;Bemdge and Irvine, 1984;Nishizuka, 1984Nishizuka, , 1986Hokin, 1985;Abdel-Latif, 1986;Downes, 1986;Williamson, 1986), including several that emphasize the nervous system (Downes, 1982(Downes, , 1983Fisher and Agranoff, 1986;Hawthorne, 1986; Nahorski et al., 1986). The present contribution emphasizes developments of neurochemical relevance since a review on the subject in this journal 8 years ago (Hawthorne and Pickard, 1979). CHEMISTRY AND ENZYMOLOGY OF INOSITOL LIPIDS AND INOSITOL PHOSPHATESThe inositol lipids Phosphatidylinositol (PI), depicted in Fig. lA, is a glycerophospholipid in which the sn-1 and sn-2 positions of glycerol are esterified to fatty acids, whereas the sn-3 position is phosphodiesterified to the 1)-1 position of myo-inositol. myo-Inositol is one of nine possible isomers of hexahydroxycyclohexane, which, in its preferred chair conformation, has one axial and five equatorial hydroxyl groups. The molecule can be likened to a turtle (Fig. 1B) in which the four legs and tail are the five equatorial hydroxyls, numbered counterclockwise from above, starting with the right foreleg as position D-1 (Fig. 1 C). The turtle's head is thus the axial hydroxyl at position D-2. The phosplhatidyl group in all of the phosphoinositides is linked to D-1 (the right foreleg).PI is synthesized in brain from a liponucleoiide intermediate, cytidine diphosphodiacylglycerol (CDP-DG) (Agranoff et al., 1958), and inositol in the presAddress correspondence and reprint requests to Dr. B. W. Agranoff at Neuroscience Laboratory Building, University of Michigan, 1103 East Huron, Ann Arbor, MI 48104-1687, U.S.A.Abbreviations used: ACh, acetylcholine; ACTH, corticotropin ( I-24)tetracosapeptide; APB, ~~-2-amino-4-phosphobutyric acid; APV, DL-2-amino-5-phosphonovalerate; CDP-DG, cytidine diphosphodiacylglycerol; DG, 1,2-diacyl-sn-glycerol; GAP, growthassociated ...

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“…Total and inorganic phosphate were measured by the method of King (27). When areas of a paper chromatogram were estimated, a trace of ammonium molybdate was added to aid digestion (Dawson [5] (23). It was used as a marker for plasma membrane.…”

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Fat Metabolism in Higher Plants

Harwood¹,

Stumpf²

1970

Plant Physiol.

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To understand more fully organelle membrane assemblage, the synthesis of the first fatty acids by the germinating pea, Pisum sativum, was studied by the incorporation of either tritiated water or acetate-1_'4C into lipids by the intact, initially dry seed. After a lag phase, labeling proceeded linearly. This lag phase ended when uptake of water had increased the seed weight to 185% of its original weight. The first fatty acids synthesized were palmitic and stearic followed shortly after by long chain saturated fatty acids (C20-C26). The synthesis of very long chain acids was consistently characteristic of several other seeds in early stages of germination. The majority of the radioactive acids were present in phospholipids and were localized in particulate fractions. The acyl components of phosphatidyl glycerol were highly labeled. (13) showed a relatively unspecific breakdown of stored fat.The use of tritiated water as a source of label for newly synthesized fatty acids provides a good alternative to the commonly used acetate. Spedding and Wilson (39) have used this isotope to study amino acid metabolism at very early stages of germination of mustard, and Foster and Katz (9) studied its incorporation into fatty acids by rat adipose tissue. Since water is intimately involved with the natural germination process, use of tritium oxide does not suffer from the criticism of using an artificial substrate. The results of its use can then be compared to the use of acetate, in case of differences.Since pea seeds are readily germinated with concomitant lipid synthesis (32), they were chosen to study the synthesis of fatty acids at very early times of germination. It is at this stage that reorganization of cell components occurs, directed to organelle formation. Thus this paper attempts to define the nature of the fatty acids and complex lipids which are synthesized by the seed as germination begins.Germination of a plant seed involves a complex series of metabolic processes such as water imbibition, respiration, nucleic acid and protein synthesis, mobilization of food reserves as well as cell differentiation and growth (33). Plant fatty acid synthesis has been studied with peas by Macey and Stumpf (32). These low lipid, high starch-containing seeds were found to incorporate acetate-1-14C into fatty acids from C16 to C28. The enzyme systems responsible for these syntheses were further studied and evidence was presented that the microsomal fraction participated in the synthesis of the very long chain fatty acids, probably from malonyl-acyl carrier protein. Either green or etiolated barley leaves also synthesized fatty acids of chain length up to C24 (17). The same authors (18) found that these acids were located in a particulate cellular fraction. Kolattukudy (28), using Brassica leaf tissue, found very long chain fatty acids produced from acetate.Partially purified enzyme preparations of fatty acid synthetase usually produced a pattern of fatty acids different from the pattern found with the endogenous fatty acid...

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The phosphatidylinositol kinase of rat brain

Cited by 135 publications

References 20 publications

The diphosphoinositide kinase of rat brain

The diphosphoinositide kinase of rat brain

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Fat Metabolism in Higher Plants

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