Phosphorylated beta-guanidinopropionate as a substitute for phosphocreatine in rat muscle

Abstract

To evaluate phosphorylated beta-guanidinopropionate (beta-GPAP) as a substitute for phosphocreatine (PC), hypoxic tibialis anterior muscles were stimulated to contract isometrically in situ until twitch tension fell to 25 percent of the peak value. Muscles from rats fed beta-guanidinopropionic acid (beta-GPA) failed to exhibit the staircase phenomenon, and they developed 28 percent less tension than control muscles. In control muscles lactate increased from 0.75 to 20.99, ADP increased from 0.89 to 1.20, ATP decreased from 5.09 to 2.73, and PC decreased from 15.78 to 1.52 mumol/g. In muscles from rats fed beta-GPA, lactate increased from 0.85 to 14.31, ADP increased from 0.86 to 1.05, ATP decreased from 2.69 to 1.71, PC decreased from 0.73 to 0.30, and beta-GPAP decreased from 30.34 to 19.45 mumol/g. From these measurements, the use of high-energy phosphate was calculated to be reduced 32 percent in muscles from rats fed beta-GPA. The relationships between the use of high-energy phosphate was calculated to be reduced 32 percent in muscles from rats fed beta-GPA. The relationships between the use of high-energy phosphate and tension development confirm experimentally the ability of beta-GPAP to substitute for PC as a source of energy to sustain muscle contraction.

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

“…Substrate analogs of Cr, e.g., p-guanidinopropionic acid ((3-GPA), a poor substrate (higher Michaelis constant and lower Vmax) for CK, have also been used to decrease PCr and ATP levels. Early studies on p-GPA-fed animals led to disparate results, with some investigations finding no effect of CK inhibition on skeletal muscle function (24) and others reporting an im pairm ent of muscle force generation during repetitive activation (10,16). More recent studies on p-GPA-fed animals demonstrate a greater im pairm ent of limb muscle isometric forcegenerating capacity during the initial series of repeti tive activation, as compared with control muscle (17).…”

“…The high level of CK activity found in skeletal muscle ensures th at, w hen consistent high-energy phosphate production is necessary during repetitive contractile activity, ATP levels will be m aintained at the expense of PCr. This role of CK as an ATP buffer is widely accepted (18, 33).Defining a physiological role for CK in skeletal muscle fatigue, however, has been difficult, with prior studies using substrate analogs (10,16,17,20) of Cr to assess the functional consequences of impaired CK activity. These studies have generated disparate re sults and exclusively examined fatigue under repetitive isometric conditions.…”

“…Defining a physiological role for CK in skeletal muscle fatigue, however, has been difficult, with prior studies using substrate analogs (10,16,17,20) of Cr to assess the functional consequences of impaired CK activity. These studies have generated disparate re sults and exclusively examined fatigue under repetitive isometric conditions.…”

Intramitochondrial inclusions caused by depletion of creatine in rat skeletal muscles.

“…Decrease in ATP could be caused by a decreased creatine content in muscle, which then decreases phosphocreatine (PC) (FITCH et al, 1974(FITCH et al, , 1975MAINWOOD et al, 19.82), due to an increased loss of creatine through urine as was found in coldacclimated rats by KURAHASHI and KUROSHIMA (1978). Therefore, the current study was performed to investigate how the ultrastructure of mitochondria respond when the contents of PC and ATP are decreased chronically.…”

“…In this study, rats were fed creatine-analogue f3-guanidinopropionic acid ,(f3-GPA) to decrease PC and ATP. Feeding f3-GPA lowers muscle creatine (SHIELDS and WHITEHAIR, 1973), PC (FITCH et al, 1974(FITCH et al, , 1975MAINWOOD et al, 1982), and ATP (FITCH et al, 1974(FITCH et al, , 1975MAINWOOD et al, 1982) because /3-GPA inhibits creatine entry into muscle from plasma (FITCH et al, 1968;SHIELDS and WHITEHAIR, 1973).…”