Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study.

Abstract

31P NMR is used to determine the relationship between work output in the exercising human forearm and the steady-state capability of oxidative phosphorylation as measured by the phosphocreatine/inorganic phosphate, ratio (PCr/Pi). Exercise intensities (one contraction per 5 sec) permitting comfortable continuation of activity for >1 hr produced PCr/Pi of about 1 for a subject ofmoderate training. Linear relationships between work rate per unit volume of muscle and the 5-min mean'PCr/ P. were found for the subject's left and right arms. The protocol affords sensitive criteria ofmuscle performance innormal subjects and of biochemical or vascular disease in abnormal subjects. The Pi, PCr, and ATP levels found by' 31P NMR represent the initial values in the cycle ofcontraction and relaxation which permit restitution of resting state 4 priorto the next contraction and the continuation of steady-state work performance.Regulation of the bioenergetic state of body tissues bt mitochondrial respiratory control (1) is exemplified in skeletal muscle by the state 4-3 response of tissue mitochondria in the oxidation of the matrix space NADH (2) and of cytochrome b (3, 4) of the frog gastrocnemius muscle in response to electrically induced contractions. Activation ofenergy metabolism has been attributed to the arrival of ADP at mitochondria or, as more recently suggested by 31P NMR studies, to the fact that increased levels of free Pi elicit the resting -* active (state transition in the tissue mitochondria (5-9). In either case, one would expect the state 4-3 transition of mitochondria to regulate the rate of ATP synthesis as the work load is increased in a linear fashion up to the point of maximum state 3 electron transport, respiration rate, and ATP production.The noninvasive 31P NMR determination of tissue Pi concentration is extended in detail to the human arm and leg in these studies and supports the earlier finding oflow Pi in resting tissue (6-9, *), confirming initial studies (10) of phosphate potential in suspensions of ascites tumor cells in which a value of 104 was found by a noninvasive optical measurement and differed by a factor of>85 from the chemical datawhich gave 103.2.Much work has been done with paired samples ofamphibian muscle by both analytical biochemistry (11) and by 31P NMR (12). In humans, however, continual biopsy and biochemical analysis are not practical because even needle biopsies cause a loss of functional muscle. The object of the present experiments was to maintain steady states ofwrist flexor work output and to determine the corresponding stimulation of mitochondrial activity by measuring the phosphocreatine (PCr)/Pi ratio in a noninvasive, nondestructive manner.The first noninvasive human studies with 31P NMR permitted only mild exercise of an extremity within the magnet (6).These studies evaluated PCr/Pi values during continuous exercise of the human wrist flexor musculature, monitored by direct coupling to the Cybex ergometer. In two other recent applications to arm exercise wi...

Increased incidence of a resonance in the phosphodiester region of 31p nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients

“…However, the repeated appearance of phosphodiester peaks in FMS patients may lend support to this theory from a different point of view. Phosphodiester resonances from compounds normally associated with cell membranes (32) occur at MRS-visible levels in normal calf muscle but are less prevalent in the forearm spectra of healthy subjects (33,34). The major compound contributing to the PDE peak in muscle is glycerol-3-phosphorylcholine (GPC) (32,33).…”

Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice.

“…The defect in ATP synthesis may be a direct consequence of a deficit in intracellular phosphate, since recent data suggest that intracellular phosphate concentration in normal skeletal muscle is not sufficient to provide maximal rates of oxidative phosphorylation (43).…”

Muscle strength mediates the relationship between mitochondrial energetics and walking performance

“…Muscle mitochondrial function can be studied by in vivo 31 P MRS, a noninvasive technique used to assess the rate of maximum in vivo oxidative capacity of skeletal muscle by quantitatively measuring phosphorus‐containing metabolites—phosphocreatine (PCr), inorganic phosphate (P i ), and adenosine triphosphate (ATP) (Chance et al ., 1981; Edwards et al ., 2012). This method is reproducible (McCully et al ., 2009), can be focused to a specific, single muscle (McCully et al ., 1993), is not affected by postural or balance impairments, and has been validated against in vitro techniques (McCully et al ., 1993; Conley et al ., 2000).…”