Intermediates of coenzyme A biosynthesis in colon tissue: Normal vs inflammatory bowel disease
Gloeckner, Janet Wilson
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Permalink
https://hdl.handle.net/2142/21167
Description
Title
Intermediates of coenzyme A biosynthesis in colon tissue: Normal vs inflammatory bowel disease
Author(s)
Gloeckner, Janet Wilson
Issue Date
1992
Doctoral Committee Chair(s)
Layman, Donald K.
Department of Study
Human and Community Development
Discipline
Human and Community Development
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Medicine and Surgery
Health Sciences, Nutrition
Language
eng
Abstract
A specific deficiency syndrome for pantothenic acid in man has not been identified. Gastrointestinal ulcers have been repeatedly produced by pantothenic acid deficiencies in many species of animals, particularly mice, rats and swine. Of particular interest is the fact that pantothenic acid deficiency in swine produces a syndrome virtually indistinguishable from chronic ulcerative colitis in humans. The inflammatory lesions in swine were associated with lowered levels of coenzyme A, the biologically active form of pantothenic acid. Colonic mucosal tissue removed from humans with chronic ulcerative colitis or Crohn's colitis has been shown to have significantly less coenzyme A activity than tissue removed from patients with noninflammatory conditions.
This study was an attempt to further investigate the role of pantothenic acid and coenzyme A in human idiopathic inflammatory bowel disease. Colon tissue, obtained at colectomy from 18 patients with chronic ulcerative colitis, 14 with Crohn's disease of the colon and 13 non-inflammatory conditions, were assayed for coenzyme A, dephosphocoenzyme A, and 4$\sp\prime$-phosphopantetheine, key intermediates in the biosynthetic pathway of coenzyme A from pantothenic acid.
Separation of the compounds was accomplished using high performance liquid chromatography. The compounds were labeled with monobromobimane for fluorescence detection and quantification. Use of this technique in this manner had not been previously reported. Preliminary studies in porcine spiral colon tissue extracts demonstrated that the method was accurate, reliable, and reproducible.
Levels of coenzyme A determined for normal human colon tissue (19 micrograms/gram tissue) were lower than previously reported. Coenzyme A level was higher in tissue from chronic ulcerative colitis patients (35 micrograms/gram tissue) and significantly higher in tissue from Crohn's disease patients (109 micrograms/gram tissue) than tissue removed from normal controls. This finding contrasts previous work showing lowered values for coenzyme A acetylation activity (used to estimate amount of the molecule) in tissue from inflammatory bowel disease patients.
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