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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

KAR  -  Aromatic alpha-keto acid reductase

Homo sapiens

 
 
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Disease relevance of KAR

  • These studies plus data obtained using a cultured human neuroblastoma cell line showed that KAR compounds displayed their cytotoxic activities at significantly higher concentrations than the mother compounds, although their antimicrotubular activities were similar in vitro [1].
  • The maximal cytotoxic activities of KAR derivatives in in vivo mice hosting leukaemia P388 or Ehrlich ascites tumour cells appeared similar to that of vinblastine or vincristine, however significant prolongation of life span could be reached with KAR derivatives only after the administration of a single dose [1].
  • The protein MabA of Mycobacterium tuberculosis is a beta-ketoacyl reductase (KAR) and catalyses one of the four steps of the fatty acid elongation system FAS-II [2].
 

High impact information on KAR

  • We then showed that this lymphocyte population, mainly CD3+CD8+, corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule [3].
  • Antibodies raised against purified chicken MDH-s equally inhibited both MDH-s and KAR in chickens and humans [4].
  • CONCLUSION: These experimental data indicated that H&NC patients have a polyclonal expansion of functionally deficient NK cells expressing KAR [5].
  • The mechanism and physiological function of presynaptic KARs have been studied most extensively at the hippocampal mossy fiber (MF)-CA3 synapse, one of the CNS regions where the highest density of KAR subunits is expressed [6].
  • KIR and KAR are expressed by decidual NK cells [7].
 

Biological context of KAR

 

Associations of KAR with chemical compounds

  • Inhibition with malate, the end product of the MDH reaction, substantially reduces or totally eliminates KAR activity [8].
 

Co-localisations of KAR

  • Starch gel electrophoresis followed by histochemical staining using either p-hydroxy-phenylpyruvic acid (HPPA) or malate as the substrate shows that KAR activity comigrates with MDH-s in all species studied except some marine species [8].
 

Other interactions of KAR

  • The bulk of the KAR activity in human blood appears to be due to MDH-s, with a minor fraction catalysed by LDH, as is the case in most other species studied [4].
  • Expression of Killer inhibitory/activatory receptors (KIR/KAR) and the CD94 receptor by decidual NK cells was also studied [7].
 

Analytical, diagnostic and therapeutic context of KAR

  • Two DG-75 sublines obtained from different sources (designated UW and KAR) were found to produce constitutively particles identified as retroviral by electron microscopy and reverse transcriptase activity [9].

References

  1. New semisynthetic vinca alkaloids: chemical, biochemical and cellular studies. Orosz, F., Comin, B., Raïs, B., Puigjaner, J., Kovács, J., Tárkányi, G., Acs, T., Keve, T., Cascante, M., Ovádi, J. Br. J. Cancer (1999) [Pubmed]
  2. Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus locks the conformational change. Cohen-Gonsaud, M., Ducasse-Cabanot, S., Quemard, A., Labesse, G. Proteins (2005) [Pubmed]
  3. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors. Le Cleach, L., Delaire, S., Boumsell, L., Bagot, M., Bourgault-Villada, I., Bensussan, A., Roujeau, J.C. Clin. Exp. Immunol. (2000) [Pubmed]
  4. Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes. Friedrich, C.A., Ferrell, R.E., Siciliano, M.J., Kitto, G.B. Ann. Hum. Genet. (1988) [Pubmed]
  5. Expansion of natural killer cells in patients with head and neck cancer: detection of "noninhibitory" (activating) killer Ig-like receptors on circulating natural killer cells. Melioli, G., Semino, C., Margarino, G., Mereu, P., Scala, M., Cangemi, G., Crocetti, E., Machì, A.M., Ferlazzo, G. Head & neck. (2003) [Pubmed]
  6. Kainate receptor-dependent presynaptic modulation and plasticity. Kamiya, H. Neurosci. Res. (2002) [Pubmed]
  7. Uterine NK cells and trophoblast HLA class I molecules. King, A., Hiby, S.E., Verma, S., Burrows, T., Gardner, L., Loke, Y.W. Am. J. Reprod. Immunol. (1997) [Pubmed]
  8. The reduction of aromatic alpha-keto acids by cytoplasmic malate dehydrogenase and lactate dehydrogenase. Friedrich, C.A., Morizot, D.C., Siciliano, M.J., Ferrell, R.E. Biochem. Genet. (1987) [Pubmed]
  9. Constitutive production of a murine retrovirus in the human B-lymphoblastoid cell line, DG-75. Raisch, K.P., Kushnaryov, V.M., Grossberg, S.E., Cashdollar, L.W. Virology (1998) [Pubmed]
 
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