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Gene Review

SLC25A21  -  solute carrier family 25 (mitochondrial...

Homo sapiens

Synonyms: Mitochondrial 2-oxodicarboxylate carrier, ODC, ODC1, Solute carrier family 25 member 21
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Disease relevance of SLC25A21

  • To assess whether an virus-specific immune defect may be associated with multiple sclerosis (MS), we have examined the ability to generate measles virus-and influenza virus-specific cytotoxic T cells (CTL) in patients with MS, normal individuals, and other disease controls (ODC) [1].
  • In human brain diseases (Alzheimer's disease, schizophrenia) certain neurones show an increased expression of ODC, the first and rate-limiting enzyme of polyamine metabolism [2].
  • During strong functional activation (kindling, epileptic seizures, neural transplantation) astrocytes and other non-neuronal cells do also express ODC and other polyamine-metabolizing enzymes [2].
  • It seems clear, however, that the induction of ODC and the resultant increase in polyamine biosynthesis are critical for the normal growth and especially for adaptive hyperplasia of the intestinal mucosa [3].
  • Maximal ODC activity and DNA synthesis in young cells (PDL = approximately 18-22) were, respectively, five-fold and six-fold greater than that in old cells (PDL = approximately 50-55), which in turn were comparable or slightly higher than that in progeria fibroblasts [4].

Psychiatry related information on SLC25A21


High impact information on SLC25A21

  • Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC) [6].
  • We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function [6].
  • However, the main cellular locus of the ODC is the neuron--both in the immature and adult central nervous system [2].
  • In intact MCF-7 cells, Int-H1-S6A,F8A was the only active peptide capable of inducing the following biological effects: (a) inhibition of cloning efficiency on plates; (b) inhibition of cell growth and induction of apoptosis in subconfluent/confluent cells; and (c) inhibition of transcription of two c-Myc-regulated genes (ODC and p53) [7].
  • PURPOSE: This study is designed to evaluate the effectiveness of ondansetron alone (OND) or in combination with 2 days of dexamethasone and 5 days of chlorpromazine (ODC) in the prevention of emetic episodes in patients receiving multiple-day cisplatin [8].

Chemical compound and disease context of SLC25A21


Biological context of SLC25A21

  • Both OND and ODC were more effective on days 1 and 2, rather than days 4 and 5, suggesting tachyphylaxis, anticipatory nausea, or delayed nausea from the first few days of cisplatin combination chemotherapy [8].
  • The polyamines (putrescine, spermidine, and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase, ODC) are important for many cell growth processes, and may play important roles in intestinal and pancreatic adaptation [3].
  • During intestinal adaptation in response to jejunectomy, lactation and pancreatico-biliary diversion (PBD), intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis [3].
  • Our results show that overexpression of Mxi1 does in fact inhibit ODC gene expression in a dose-dependent manner both in vivo and in vitro [13].
  • Serum stimulation caused increases of ODC and DNA synthesis in IMR-90 human diploid fibroblasts, with maximal values occurring, respectively, 10 hr and 22 hr after serum stimulation [4].

Anatomical context of SLC25A21

  • We have earlier shown that expression of trypanosomal ODC in an ODC-deficient variant of CHO cells (C55.7) supported growth of these otherwise polyamine auxotrophic cells [14].
  • In all cell lines the promoter region of the ODC gene appeared to be heavily methylated, whereas the first long intron was unmethylated [15].
  • Vero cell ODC activity was elevated tenfold above basal levels when confluent cells were incubated for 5 hr in EBSS alone [16].
  • The rank orders were Barrett's > small bowel congruent to normal esophagus > gastric tissue for ODC activities, and small bowel > or = Barrett's congruent to normal esophagus > gastric tissue for putrescine contents [17].
  • In the present work, we tested the effects of 3 nitric oxide (NO) donors, namely, sodium nitroprusside (SNP), (Z)-1-(N-methyl-N-[6-(N-methylammoniohexyl)amino] diazen-1-ium-1,2-diolate (MAHMA/NO) and 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium (DEA/NO), on ODC activity in human-colon carcinoma cells (HT-29) [18].

Associations of SLC25A21 with chemical compounds


Analytical, diagnostic and therapeutic context of SLC25A21


  1. Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis. Jacobson, S., Flerlage, M.L., McFarland, H.F. J. Exp. Med. (1985) [Pubmed]
  2. The cellular localization of the L-ornithine decarboxylase/polyamine system in normal and diseased central nervous systems. Bernstein, H.G., Müller, M. Prog. Neurobiol. (1999) [Pubmed]
  3. Polyamines in intestinal and pancreatic adaptation. Luk, G.D., Yang, P. Gut (1987) [Pubmed]
  4. Changes of serum-induced ornithine decarboxylase activity and putrescine content during aging of IMR-90 human diploid fibroblasts. Chen, K.Y., Chang, Z.F., Liu, A.Y. J. Cell. Physiol. (1986) [Pubmed]
  5. DSM-III personality disorders in generalized anxiety, panic/agoraphobia, and obsessive-compulsive disorders. Mavissakalian, M.R., Hamann, M.S., Abou Haidar, S., de Groot, C.M. Comprehensive psychiatry. (1993) [Pubmed]
  6. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Suchi, M., Mizuno, H., Kawai, Y., Tsuboi, T., Sumi, S., Okajima, K., Hodgson, M.E., Ogawa, H., Wada, Y. Am. J. Hum. Genet. (1997) [Pubmed]
  7. Inhibition of cancer cell growth and c-Myc transcriptional activity by a c-Myc helix 1-type peptide fused to an internalization sequence. Giorello, L., Clerico, L., Pescarolo, M.P., Vikhanskaya, F., Salmona, M., Colella, G., Bruno, S., Mancuso, T., Bagnasco, L., Russo, P., Parodi, S. Cancer Res. (1998) [Pubmed]
  8. Ondansetron versus ondansetron, dexamethasone, and chlorpromazine in the prevention of nausea and vomiting associated with multiple-day cisplatin chemotherapy. Fox, S.M., Einhorn, L.H., Cox, E., Powell, N., Abdy, A. J. Clin. Oncol. (1993) [Pubmed]
  9. Polyamines and growth regulation of cultured human breast cancer cells by 17 beta-oestradiol. Hoggard, N., Green, C.D. Mol. Cell. Endocrinol. (1986) [Pubmed]
  10. Nonsteroidal anti-inflammatory drugs stimulate spermidine/spermine acetyltransferase and deplete polyamine content in colon cancer cells. Turchanowa, L., Dauletbaev, N., Milovic, V., Stein, J. Eur. J. Clin. Invest. (2001) [Pubmed]
  11. Potassium channel blockers quinidine and caesium halt cell proliferation in C6 glioma cells via a polyamine-dependent mechanism. Weiger, T.M., Colombatto, S., Kainz, V., Heidegger, W., Grillo, M.A., Hermann, A. Biochem. Soc. Trans. (2007) [Pubmed]
  12. Alternative antiglycation mechanisms: are spermine and fructosamine-3-kinase part of a carbonyl damage control pathway? Gugliucci, A. Med. Hypotheses (2005) [Pubmed]
  13. Overexpression of Mxi1 inhibits the induction of the human ornithine decarboxylase gene by the Myc/Max protein complex. Wu, S., Peña, A., Korcz, A., Soprano, D.R., Soprano, K.J. Oncogene (1996) [Pubmed]
  14. Importance of polyamines in cell cycle kinetics as studied in a transgenic system. Nasizadeh, S., Myhre, L., Thiman, L., Alm, K., Oredsson, S., Persson, L. Exp. Cell Res. (2005) [Pubmed]
  15. Certain changes in ornithine decarboxylase gene methylation accompany gene amplification. Wahlfors, J. Biochem. J. (1991) [Pubmed]
  16. Glucose elevates ornithine decarboxylase expression in Vero cells. Lundgren, D.W., Prokay, S.L. J. Cell. Physiol. (1988) [Pubmed]
  17. Gastrointestinal tissue polyamine contents of patients with Barrett's esophagus treated with alpha-difluoromethylornithine. Gerner, E.W., Garewal, H.S., Emerson, S.S., Sampliner, R.E. Cancer Epidemiol. Biomarkers Prev. (1994) [Pubmed]
  18. Differential inhibitory effects of three nitric oxide donors on ornithine decarboxylase activity in human colon carcinoma cells. Blachier, F., Briand, D., Selamnia, M., Robert, V., Guihot, G., Mayeur, C. Biochem. Pharmacol. (1998) [Pubmed]
  19. Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. Fiermonte, G., Dolce, V., Palmieri, L., Ventura, M., Runswick, M.J., Palmieri, F., Walker, J.E. J. Biol. Chem. (2001) [Pubmed]
  20. Changes in inducibility of ornithine decarboxylase activity in differentiating human neuroblastoma cells. Mattsson, M.E., Ruusala, A.I., Påhlman, S. Exp. Cell Res. (1984) [Pubmed]
  21. Oxygen availability during orthotopic liver transplantation. Kostopanagiotou, G., Smyrniotis, V., Theodoraki, K., Skalkidis, Y., Heaton, N., Potter, D. Liver Transpl. (2003) [Pubmed]
  22. Chronic exposure to dexamethasone induces hypomethylation of ornithine decarboxylase genes in a human myeloma cell line. Leinonen, P., Alhonen-Hongisto, L., Laine, R., Jänne, O.A., Jänne, J. FEBS Lett. (1987) [Pubmed]
  23. Biochemical markers in colorectal cancer: diagnostic and therapeutic implications. Luk, G.D., Desai, T.K., Conteas, C.N., Moshier, J.A., Silverman, A.L. Gastroenterol. Clin. North Am. (1988) [Pubmed]
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