Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues

Meaghan Anne Neill, Judy L. Aschner, Frederick Barr, Marshall L. Summar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The urea cycle and nitric oxide cycle play significant roles in complex biochemical and physiologic reactions. These cycles have distinct biochemical goals including the clearance of waste nitrogen; the production of the intermediates ornithine, citrulline, and arginine for the urea cycle; and the production of nitric oxide for the nitric oxide pathway. Despite their disparate functions, the two pathways share two enzymes, argininosuccinic acid synthase and argininosuccinic acid lyase, and a transporter, citrin. Studying the gene expression of these enzymes is paramount in understanding these complex biochemical pathways. Here, we examine the expression of genes involved in the urea cycle and the nitric oxide cycle in a panel of eleven different tissue samples obtained from individual adults without known inborn errors of metabolism. In this study, the pattern of co-expressed enzymes provides a global view of the metabolic activity of the urea and nitric oxide cycles in human tissues. Our results show that these transcripts are differentially expressed in different tissues. Using the co-expression profiles, we discovered that the combination of expression of enzyme transcripts as detected in our study, might serve to fulfill specific physiologic function(s) including urea production/nitrogen removal, arginine/citrulline production, nitric oxide production, and ornithine production. Our study reveals the importance of studying not only the expression profile of an enzyme of interest, but also studying the expression profiles of the other enzymes involved in a particular pathway so as to better understand the context of expression. The tissue patterns we observed highlight the variety of important functions of these enzymes and provides insight into the many clinical observations that result from their disruption. These results have implications for the management of urea cycle patients and raise considerations for the care of those patients receiving liver transplants. Finally, this work reaffirms the concept that the co-expression of a few genes can significantly impact complex biochemical and physiologic processes.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalMolecular Genetics and Metabolism
Volume97
Issue number2
DOIs
StatePublished - Jun 2009
Externally publishedYes

Fingerprint

Urea
Nitric Oxide
Genes
Tissue
Polymerase Chain Reaction
Enzymes
Argininosuccinic Acid
Citrulline
Ornithine
Arginine
Biochemical Phenomena
Nitrogen
Gene Expression
Inborn Errors Metabolism
Transplants
Nitrogen removal
Lyases
Metabolism
Gene expression
Liver

Keywords

  • Arginine
  • Citrulline
  • Expression
  • Liver
  • Nitric oxide
  • qRT-PCR
  • RNA
  • Urea cycle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues. / Neill, Meaghan Anne; Aschner, Judy L.; Barr, Frederick; Summar, Marshall L.

In: Molecular Genetics and Metabolism, Vol. 97, No. 2, 06.2009, p. 121-127.

Research output: Contribution to journalArticle

Neill, Meaghan Anne ; Aschner, Judy L. ; Barr, Frederick ; Summar, Marshall L. / Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues. In: Molecular Genetics and Metabolism. 2009 ; Vol. 97, No. 2. pp. 121-127.
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