Murine Ornithine Transcarbamylase: Structure and Expression

  • Steven E. Scherer
  • Gabor Veres
  • William J. Craigen
  • Stephen N. Jones
  • C. Thomas Caskey
Part of the NATO ASI Series book series (NATO ASI, volume 169)


The hepatic enzyme ornithine transcarbamylase (OTC) (EC catalyses the condensation of carbamyl phosphate and ornithine to form citrulline (Gisolia and Cohen, 1952; Jones et al., 1961). This is the second step of the mammalian urea cycle involved in the detoxification of ammonia and biosynthesis of urea. OTC is encoded on the X chromosome (Lindgren et al., 1984) and expressed primarily in liver and to a lesser extent in small bowel. The enzyme is synthesized in the cytoplasm as a 41 kD precursor and then transported to the mitochondria where a 32 amino acid leader peptide is cleaved and trimers associate within the matrix to form the active enzyme (Conboy et al., 1979; Mori et al., 1982). OTC deficiency is the most common urea cycle defect in humans and results in a severe and often fatal neonatal ammonia intoxication in hemizygous males (Walser, 1983). Female heterozygotes display a variable phenotype based on the severity of the mutation and random X-chromosome inactivation. Treatment of affected infants has been confined to restricted protein intake, peritoneal dialysis and administration of amino acid acylating agents such as benzoate, butyrate, or phenylacetate (Batshaw, 1982; Batshaw, 1981; Brusilow et al. 1984). Long-term outlook, particularly for affected males is poor, evidenced by the high incidence of mental retardation and cerebral palsy while hyperammoneimic episodes often lead to coma and death (Msall et al., 1984). Prenatal diagnosis has been largely confined to restriction fragment length polymorphism (RFLP) analysis (Fox et al., 1986; Nussbaum et al., 1986) as amniocytes do not express the enzyme, there are no metabolic products of the disorder present in amniotic fluid, and fetal liver biopsy poses a high risk to both mother and fetus.


Chloramphenicol Acetyl Transferase Ornithine Transcarbamylase Chloramphenicol Acetyl Transferase Activity Ornithine Carbamoyl Transferase Chloramphenicol Acetyl Transferase Expression 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Steven E. Scherer
    • 1
  • Gabor Veres
    • 1
  • William J. Craigen
    • 1
  • Stephen N. Jones
    • 1
  • C. Thomas Caskey
    • 1
  1. 1.Institute for Molecular Genetics, Howard Hughes Medical InstituteBaylor College of MedicineHoustonUSA

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