Date of Award

1980

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology and Toxicology

Department

Pharmacology and Toxicology

First Advisor

Paul T. Carroll

Abstract

The choline analog homocholine is not acetylated in vitro by choline-0-acetyltransferase (ChAT, EC 2.3. 1.6) which is solubilized by 100 mM sodium phosphate buffer washes of a crude vesicular fraction of mouse forebrain. However, both homocholine and choline are acetylated by a form of ChAT which is non-ionically associated with a subcellular fraction of mouse forebrain containing membrane associated organelles and occluded ACh (P 4 ). Acetylation of homocholine by membrane associated ChAT is saturable. 4-(l-Naphthylvinyl) pyridine (NVP) inhibits the acetylation of both choline (60%) and homocholine (40%) by membrane associated ChAT but reduces the acetylation of only choline by soluble ChAT (76%). Choline and homocholine serve as competitive alternative substrates for the same membrane associated ChAT whereas homocholine only acts as a competitive inhibitor of choline acetylation by soluble ChAT. Acetylhomocholine competitively inhibits the acetylation of choline by both soluble and membrane associated ChAT more dramatically than does the natural end product ACh.

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