4-Phenyl-3-butenoic acid, an in vivo inhibitor of peptidylglycine hydroxylase (peptide amidating enzyme)

A. F. Bradbury, J. Mistry, B. A. Roos, D. G. Smyth

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The ability of a series of non-peptide carboxylic acids to act as substrates or inhibitors of the peptide-amidating enzyme (peptidyl-glycine hydroxylase) was assessed by determining their ability to reduce the rate of enzymic conversion of D-tyrosyl-valyl-glycine or D-tyrosyl-phenylalanyl-glycine to the corresponding dipeptide amide. The inclusion of a phenyl substituent in a position distal to the carboxyl group promoted the inhibitory action. The inhibition was found to be irreversible when an olefinic double bond, α or β to the carboxyl group, was present in the molecule; the inhibition appeared to be associated with a covalent interaction between the amidating enzyme and the inhibitor. With 4-phenyl-3-butenoic acid the inhibitory properties were manifest only in the presence of cofactros of the enzyme. When 4-phenyl-3-[2-14C]butenoic acid was used, the radioactivity was shown to be incorporated into protein that co-chromatographed with active enzyme. Incubation of rat thyroid carcinoma CA77 cells in the presence of 4-phenyl-3-butenoic acid led to a decrease in the levels of intracellular amidating activity and of thyrotropin-releasing hormone, an amidated peptide produced by these cells. The inhibitory effects reached a maximum at approximately 15 h after which the enzyme levels returned to the control values even though the concentration of 4-phenyl-3-butenoic acid in the cells remained unchanged. The results indicate that a mechanism exists in these cells for regulation of amidating activity.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalEuropean Journal of Biochemistry
Volume189
Issue number2
StatePublished - May 21 1990
Externally publishedYes

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Glycine
Peptides
Enzymes
Crotonates
Thyrotropin-Releasing Hormone
Dipeptides
Radioactivity
Enzyme Inhibitors
Carboxylic Acids
Mixed Function Oxygenases
Thyroid Neoplasms
Amides
Rats
Molecules
Acids
4-phenyl-3-butenoic acid
peptidylglycine monooxygenase
Substrates
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

4-Phenyl-3-butenoic acid, an in vivo inhibitor of peptidylglycine hydroxylase (peptide amidating enzyme). / Bradbury, A. F.; Mistry, J.; Roos, B. A.; Smyth, D. G.

In: European Journal of Biochemistry, Vol. 189, No. 2, 21.05.1990, p. 363-368.

Research output: Contribution to journalArticle

Bradbury, A. F. ; Mistry, J. ; Roos, B. A. ; Smyth, D. G. / 4-Phenyl-3-butenoic acid, an in vivo inhibitor of peptidylglycine hydroxylase (peptide amidating enzyme). In: European Journal of Biochemistry. 1990 ; Vol. 189, No. 2. pp. 363-368.
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