Systematic study of the hydrolysis of 4-methylumbelliferylguanidinobenzoate in plasma from patients with cystic fibrosis and controls.

Abstract

In contrast to the original reports by others, the hydrolysis of 4-methylumbelliferylguanidinobenzoate ((MUGB), and active-site titrant of serine proteases, was found not to be significantly different in plasma samples from patients with cystic fibrosis (CF), obligate heterozygotes, and normal controls. Since the steady-state turnover of substrate is the dominant term of MUGB hydrolysis, the assay in its present form does not meet the requirements of an active-site titration. The reproducibility and reliability of the assay are hampered by (1) high blank values due to non-specific hydrolysis, (2) the absence of a defined endpoint of the incubation, (3) the non-linearity of the assay with respect to plasma concentration, (4) the temperature-dependent evolution of esterase activity during incubation, and (5) most importantly the loss of activity during storage of plasma samples. Cleavage of MUGB catalysed by the imidazole ring of histidine accounts for a significant portion of the activity in plasma.

• Authors: B Tümmler, E Seger, J R Riordan
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 125 Issue 2 Pg. 219-32 (Oct 27 1982) ISSN: 0009-8981 [Print] Netherlands
• PMID: 6754142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-methylumbelliferylguanidinobenzoate
• Umbelliferones
• Hymecromone
• Histidine
• Peptide Hydrolases

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Cystic Fibrosis (blood, diagnosis)
• Drug Stability
• Enzyme Activation
• Female
• Histidine (blood)
• Humans
• Hydrolysis
• Hymecromone (analogs & derivatives, blood)
• Kinetics
• Male
• Methods
• Peptide Hydrolases (blood)
• Umbelliferones (blood)