Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 May;85(10):3494–3498. doi: 10.1073/pnas.85.10.3494

Isolation and characterization of cDNA clones encoding human liver glutamate dehydrogenase: evidence for a small gene family.

G Mavrothalassitis 1, G Tzimagiorgis 1, A Mitsialis 1, V Zannis 1, A Plaitakis 1, J Papamatheakis 1, N Moschonas 1
PMCID: PMC280238  PMID: 3368458

Abstract

We have isolated a series of human liver cDNA clones encoding glutamate dehydrogenase. The cDNA-derived protein sequence specifies a single 558-amino acid long polypeptide including a cleavable signal sequence of 53 amino acids. Blotting analysis of RNA from human, monkey, and rabbit showed that glutamate dehydrogenase mRNA is present in various amounts in all tissues tested. Glutamate dehydrogenase mRNAs are of four sizes and are found in different ratios in different tissues; the predominant ones are approximately 3.5 and approximately 2.9 kilobases. Blot hybridization of human genomic DNA to nonoverlapping cDNA fragments revealed multiple bands, many of which hybridize with two or more probes in a manner inconsistent with the existence of a single GLUD gene. Moreover, two separate 36-base synthetic oligonucleotides corresponding to the coding region hybridize to multiple genomic fragments, confirming the existence of more than one GLUD-related gene in human.

Full text

PDF
3494

Images in this article

3497Image
on p.3497
3498Image
on p.3498
3498Image
on p.3498
3498Image
on p.3498

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banner C., Silverman S., Thomas J. W., Lampel K. A., Vitkovic L., Huie D., Wenthold R. J. Isolation of a human brain cDNA for glutamate dehydrogenase. J Neurochem. 1987 Jul;49(1):246–252. doi: 10.1111/j.1471-4159.1987.tb03422.x. [DOI] [PubMed] [Google Scholar]
  2. Berl S. Cerebral amino acid metabolism in hepatic coma. Exp Biol Med. 1971;4:71–84. [PubMed] [Google Scholar]
  3. Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cladaras C., Hadzopoulou-Cladaras M., Nolte R. T., Atkinson D., Zannis V. I. The complete sequence and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms. EMBO J. 1986 Dec 20;5(13):3495–3507. doi: 10.1002/j.1460-2075.1986.tb04675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colon A. D., Plaitakis A., Perakis A., Berl S., Clarke D. D. Purification and characterization of a soluble and a particulate glutamate dehydrogenase from rat brain. J Neurochem. 1986 Jun;46(6):1811–1819. doi: 10.1111/j.1471-4159.1986.tb08500.x. [DOI] [PubMed] [Google Scholar]
  7. Dennis S. G., Clark J. B. The synthesis of glutamate by rat brain mitochondria. J Neurochem. 1978 Sep;31(3):673–680. doi: 10.1111/j.1471-4159.1978.tb07839.x. [DOI] [PubMed] [Google Scholar]
  8. Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochem. 1984 Jan;42(1):1–11. doi: 10.1111/j.1471-4159.1984.tb09689.x. [DOI] [PubMed] [Google Scholar]
  9. Goossens M., Kan Y. Y. DNA analysis in the diagnosis of hemoglobin disorders. Methods Enzymol. 1981;76:805–817. doi: 10.1016/0076-6879(81)76159-7. [DOI] [PubMed] [Google Scholar]
  10. Hanauer A., Mattei M. G., Mandel J. L. Presence of a TaqI polymorphism in the human glutamate dehydrogenase (GLUD) gene on chromosome 10. Nucleic Acids Res. 1987 Aug 11;15(15):6308–6308. doi: 10.1093/nar/15.15.6308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Julliard J. H., Smith E. L. Partial amino acid sequence of the glutamate dehydrogenase of human liver and a revision of the sequence of the bovine enzyme. J Biol Chem. 1979 May 10;254(9):3427–3438. [PubMed] [Google Scholar]
  12. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  13. Kozak M. Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes. Mol Cell Biol. 1987 Oct;7(10):3438–3445. doi: 10.1128/mcb.7.10.3438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maeda N., Bliska J. B., Smithies O. Recombination and balanced chromosome polymorphism suggested by DNA sequences 5' to the human delta-globin gene. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5012–5016. doi: 10.1073/pnas.80.16.5012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McGeer E. G., McGeer P. L. Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature. 1976 Oct 7;263(5577):517–519. doi: 10.1038/263517a0. [DOI] [PubMed] [Google Scholar]
  16. Mihara K., Omura T., Harano T., Brenner S., Fleischer S., Rajagopalan K. V., Blobel G. Rat liver L-glutamate dehydrogenase, malate dehydrogenase, D-beta-hydroxybutyrate dehydrogenase, and sulfite oxidase are each synthesized as larger precursors by cytoplasmic free polysomes. J Biol Chem. 1982 Apr 10;257(7):3355–3358. [PubMed] [Google Scholar]
  17. Mohana Rao J. K., Argos P. A conformational preference parameter to predict helices in integral membrane proteins. Biochim Biophys Acta. 1986 Jan 30;869(2):197–214. doi: 10.1016/0167-4838(86)90295-5. [DOI] [PubMed] [Google Scholar]
  18. Olney J. W., Ho O. L., Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res. 1971;14(1):61–76. doi: 10.1007/BF00234911. [DOI] [PubMed] [Google Scholar]
  19. Plaitakis A., Berl S., Yahr M. D. Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol. 1984 Feb;15(2):144–153. doi: 10.1002/ana.410150206. [DOI] [PubMed] [Google Scholar]
  20. Plaitakis A., Nicklas W. J., Desnick R. J. Glutamate dehydrogenase deficiency in three patients with spinocerebellar syndrome. Ann Neurol. 1980 Apr;7(4):297–303. doi: 10.1002/ana.410070403. [DOI] [PubMed] [Google Scholar]
  21. Rothman S. Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci. 1984 Jul;4(7):1884–1891. doi: 10.1523/JNEUROSCI.04-07-01884.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  24. Wieloch T. Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science. 1985 Nov 8;230(4726):681–683. doi: 10.1126/science.2996146. [DOI] [PubMed] [Google Scholar]
  25. Yu A. C., Schousboe A., Hertz L. Metabolic fate of 14C-labeled glutamate in astrocytes in primary cultures. J Neurochem. 1982 Oct;39(4):954–960. doi: 10.1111/j.1471-4159.1982.tb11482.x. [DOI] [PubMed] [Google Scholar]
  26. Zannis V. I., Cole F. S., Jackson C. L., Kurnit D. M., Karathanasis S. K. Distribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages. Biochemistry. 1985 Jul 30;24(16):4450–4455. doi: 10.1021/bi00337a028. [DOI] [PubMed] [Google Scholar]
  27. Zannis V. I., Kurnit D. M., Breslow J. L. Hepatic apo-A-I and apo-E and intestinal apo-A-I are synthesized in precursor isoprotein forms by organ cultures of human fetal tissues. J Biol Chem. 1982 Jan 10;257(1):536–544. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES