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Gene Review

NAT8  -  N-acetyltransferase 8 (GCN5-related,...

Homo sapiens

Synonyms: ATase2, Acetyltransferase 2, CCNAT, CML1, Camello-like protein 1, ...
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Disease relevance of NAT8

  • Vitamin K deficiency, drugs that act as vitamin K antagonists, and oxidant stress are forces that could prevent the formation of GLA residues on MGP [1].
  • Serum osteocalcin (BGP), a vitamin K-dependent gamma-carboxyglutamic acid (GLA) containing bone protein, provides an index of bone turnover in patients with a variety of metabolic bone diseases [2].
  • GLA obese had lower body weight (p<0.0001) and 60-day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups [3].
  • Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity [3].
  • Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats [3].

High impact information on NAT8

  • Based on these data, we propose that the two high affinity sites of human Factor Xa consist of two paired GLA residues; GLA-19, GLA-20 and GLA-25, GLA-26 together with one of the remaining single GLA residues for each site [4].
  • Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene [5].
  • In this report, we describe the full-length genome sequences of two novel SIVs, designated SIVmon-99CMCML1 and SIVmus-01CM1085, isolated from one mona (CML1) and one mustached (1085) monkey, respectively [6].
  • To identify the constituent proteins of higher plant cells structurally homologous to the vertebrate nuclear lamina, we cloned overlapping cDNAs partially encoding a CML-1-recognized protein and determined the entire sequence including the open reading frame [7].
  • A monoclonal antibody, CML-1, raised against carrot (Daucus carota L.) nuclear-matrix proteins selectively labeled the nuclear periphery of carrot protoplasts when visualized by confocal and electron microscopy [7].

Chemical compound and disease context of NAT8


Biological context of NAT8

  • For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05) [3].
  • Isobole analysis at the isoeffect levels of 50 and 70% revealed that drug interaction was predominantly synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell cultures [8].
  • Nude mice bearing subcutaneous pancreatic tumours produced with the MIA PaCa-2 cell line were treated with the maximum tolerated dose (6.75 mg GLA and 7.3 mg EPA per g of body weight) administered over 10 days by daily intravenous (i.v.) bolus injections [11].
  • We hypothesize that the anti-inflammatory effects of EPA and GLA may be due, in part, to induction of neutrophil apoptosis [9].
  • EPA, GLA, and various combinations of EPA and GLA significantly induced apoptosis and reduced cell viability in HL-60 cells [9].

Anatomical context of NAT8

  • GLA preincubation followed by paclitaxel resulted in additivity for all cell lines [8].
  • The purpose of this study was to determine whether EPA and GLA, alone or in combination, trigger apoptotic cell death in the human promyelocytic leukemia HL-60 cell line [9].
  • These observations suggest that prolonged survival in CML 1) is not contingent upon intensive treatment resulting in marrow hypoplasia, and 2) does not require the persistence of a clone of karyotypically-normal bone marrow cells or a clone of marrow cells in males which has lost the Y chromosome [12].
  • The presence of the amino acid gamma-carboxyglutamate (GLA) was established in human middle ear bones [13].
  • The GLA content of human incus, malleus, and stapes with 1-2 nmol/mg bone is in the range previously reported for a variety of bone [13].

Associations of NAT8 with chemical compounds

  • The deuterium isotope effect on the reciprocal lifetime (tau-1) of excited Eu(III) in human Factor Xa has indicated that 2 to 3 water molecules remain on Eu(III) after being complexed by Factor Xa, suggesting that 3-6 ligand atoms are provided by the protein, probably through two or three gamma-carboxyglutamic acids (GLA) [4].
  • We have examined the combined in vitro cytotoxicity of paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells [8].
  • Fifty children were randomized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of double-blind parallel treatment [14].
  • Fourteen species of the genus Echium (Fam. Boraginaceae) collected in the Macaronesia were surveyed in a search for high levels of gamma-linolenic acid (GLA, 18:3omega6) in the seed oil [15].
  • In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats [16].

Regulatory relationships of NAT8

  • Furthermore, CML-1 inhibited TNF-alpha-induced IkB kinase activation, subsequent degradation of IkBalpha, and nuclear translocation of NK-kB [17].

Analytical, diagnostic and therapeutic context of NAT8

  • Nineteen hypercholesterolemic patients (10 without and 9 with hypertriglyceridemia) were given evening primrose oil rich in gammalinolenic acid (GLA, 18: 3n - 6), in a placebo controlled cross-over design, over 16 weeks (8 + 8 weeks), with safflower oil as the placebo [18].
  • Allylamine (ALAM) film was plasma-polymerized on a flat glass (referred to as ALAM(GLA): GLA refers to a flat glass plate) for use as a solid phase in two-site immunoradiometric assay (two-site IRMA) [19].
  • Although no differences were seen for the AUC of the appetite profile, aet 15:00 h subjects were less satiated with LA (46.1+/-6.2 mm, P<0.05) or GLA (45.1+/-5.8 mm, P<0.01) than after treatment OA (62.5+/-4.8 mm) [20].


  1. Arterial calcification: a review of mechanisms, animal models, and the prospects for therapy. Wallin, R., Wajih, N., Greenwood, G.T., Sane, D.C. Medicinal research reviews. (2001) [Pubmed]
  2. Serum and dialysate osteocalcin levels in hemodialysis and peritoneal dialysis patients and after renal transplantation. Epstein, S., Traberg, H., Raja, R., Poser, J. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  3. Time-dependent effects of progressive gamma-linolenate feeding on hyperphagia, weight gain, and erythrocyte fatty acid composition during growth of Zucker obese rats. Thurmond, D.C., Tang, A.B., Nakamura, M.T., Stern, J.S., Phinney, S.D. Obes. Res. (1993) [Pubmed]
  4. Laser-induced lanthanide luminescence as a probe of metal ion-binding sites of human Factor Xa. Rhee, M.J., Horrocks, W.D., Kosow, D.P. J. Biol. Chem. (1984) [Pubmed]
  5. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. Kotanko, P., Kramar, R., Devrnja, D., Paschke, E., Voigtländer, T., Auinger, M., Pagliardini, S., Spada, M., Demmelbauer, K., Lorenz, M., Hauser, A.C., Kofler, H.J., Lhotta, K., Neyer, U., Pronai, W., Wallner, M., Wieser, C., Wiesholzer, M., Zodl, H., Födinger, M., Sunder-Plassmann, G. J. Am. Soc. Nephrol. (2004) [Pubmed]
  6. Identification of a new simian immunodeficiency virus lineage with a vpu gene present among different cercopithecus monkeys (C. mona, C. cephus, and C. nictitans) from Cameroon. Courgnaud, V., Abela, B., Pourrut, X., Mpoudi-Ngole, E., Loul, S., Delaporte, E., Peeters, M. J. Virol. (2003) [Pubmed]
  7. Peripheral framework of carrot cell nucleus contains a novel protein predicted to exhibit a long alpha-helical domain. Masuda, K., Xu, Z.J., Takahashi, S., Ito, A., Ono, M., Nomura, K., Inoue, M. Exp. Cell Res. (1997) [Pubmed]
  8. Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Menéndez, J.A., del Mar Barbacid, M., Montero, S., Sevilla, E., Escrich, E., Solanas, M., Cortés-Funes, H., Colomer, R. Eur. J. Cancer (2001) [Pubmed]
  9. Eicosapentaenoic acid and gamma-linolenic acid induce apoptosis in HL-60 cells. Gillis, R.C., Daley, B.J., Enderson, B.L., Karlstad, M.D. J. Surg. Res. (2002) [Pubmed]
  10. Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential. Pasqualini, M.E., Heyd, V.L., Manzo, P., Eynard, A.R. Prostaglandins Leukot. Essent. Fatty Acids (2003) [Pubmed]
  11. Effect of 1-(gamma)linolenyl-3-eicosapentaenoyl propane diol on the growth of human pancreatic carcinoma in vitro and in vivo. Ravichandran, D., Cooper, A., Johnson, C.D. Eur. J. Cancer (2000) [Pubmed]
  12. Factors associated with prolonged survival in chronic myeloid leukemia. Wolf, D.J., Silver, R.T., Coleman, M. Cancer (1978) [Pubmed]
  13. Gamma-carboxyglutamate in normal and pathological human middle ear bones. Zajic, G., Graham, M.D., Schacht, J. Archives of oto-rhino-laryngology. (1984) [Pubmed]
  14. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Stevens, L., Zhang, W., Peck, L., Kuczek, T., Grevstad, N., Mahon, A., Zentall, S.S., Arnold, L.E., Burgess, J.R. Lipids (2003) [Pubmed]
  15. Occurrence and characterization of oils rich in gamma-linolenic acid (III): the taxonomical value of the fatty acids in Echium (Boraginaceae). Guil-Guerrero, J.L., Gómez-Mercado, F., Rodríguez-García, I., Campra-Madrid, P., García-Maroto, F. Phytochemistry (2001) [Pubmed]
  16. Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. Mohan, I.K., Das, U.N. Prostaglandins Leukot. Essent. Fatty Acids (2000) [Pubmed]
  17. CML-1 inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in endothelial cells through inhibition of IkBalpha kinase. Mo, S.J., Son, E.W., Lee, S.R., Lee, S.M., Shin, D.H., Pyo, S. Journal of ethnopharmacology (2007) [Pubmed]
  18. Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins. Ishikawa, T., Fujiyama, Y., Igarashi, O., Morino, M., Tada, N., Kagami, A., Sakamoto, T., Nagano, M., Nakamura, H. Atherosclerosis (1989) [Pubmed]
  19. Plasma-polymerized allylamine film used as a new solid phase in immunoradiometric assay (IRMA): effect of antibody (F(ab')2 fragment) concentration on dose response in two-site IRMA. Muratsugu, M., Kurosawa, S., Mori, Y., Kamo, N. Chem. Pharm. Bull. (1992) [Pubmed]
  20. Fat-specific satiety in humans for fat high in linoleic acid vs fat high in oleic acid. Kamphuis, M.M., Westerterp-Plantenga, M.S., Saris, W.H. European journal of clinical nutrition. (2001) [Pubmed]
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