title: Molecular and kinetic alterations of muscle AMP deaminase during chronic creatine depletion.
abstract: We examined a possible mechanism to account for the maintenance of peak AMP deamination rate in fast-twitch muscle of rats fed the creatine analog beta-guanidinopropionic acid (beta-GPA), in spite of reduced abundance of the enzyme AMP deaminase (AMPD). AMPD enzymatic capacity (determined at saturating AMP concentration) and AMPD protein abundance (Western blot) were coordinately reduced approximately 80% in fast-twitch white gastrocnemius muscle by beta-GPA feeding over 7 wk. Kinetic analysis of AMPD in the soluble cell fraction demonstrated a single Michaelis-Menten constant (Km; approximately 1.5 mM) in control muscle extracts. An additional high-affinity Km (approximately 0.03 mM) was revealed at low AMP concentrations in extracts of beta-GPA-treated muscle. The kinetic alteration in AMPD reflects increased molecular activity at low AMP concentrations; this could account for high rates of deamination in beta-GPA-treated muscle in situ, despite the loss of AMPD enzyme protein. The elimination of this kinetic effect by treatment of beta-GPA-treated muscle extracts with acid phosphatase in vitro suggests that phosphorylation is involved in the kinetic control of skeletal muscle AMPD in vivo.
authors.affiliation: Department of Physiology, State University of New York Health Science Center, Syracuse 13210, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Rush
authors.forename: P C
authors.initials: PC
authors.lastname: Tullson
authors.forename: R L
authors.initials: RL
authors.lastname: Terjung
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003401:Creatine / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006146:Guanidines; D011422:Propionates; D000249:Adenosine Monophosphate; D000659:AMP Deaminase; D003401:Creatine; C005775:guanidinopropionic acid