Homocysteine induces energy imbalance in rat skeletal muscle: Is creatine a protector?

Abstract

Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

Anti-fatigue effects of dietary nucleotides in mice

“…In the present study, the activities of SDH, Na + -K + -ATPase, and Ca 2+ -Mg2 + -ATPase were measured to evaluate mitochondrial function. Energy metabolism includes anabolism and catabolism, involving many biological enzymes [27]. Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase are the two main ATP degradation enzymes, which can hydrolyze ATP to supply direct free energy [28].…”

“…Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase are among the main factors responsible for fatigue [30–32]. In addition, SDH is a rate-limiting enzyme associated with the regulation of the glycolytic pathway and the Krebs cycle and the catalysis of ATP synthesis [27]. The activities of these enzymes may be important in energy metabolism in the skeletal muscle under fatigue.…”

Plasma homocysteine level is a risk factor for osteoporotic fractures in elderly patients

“…We found in this study that, in the OPF group, 25 (OH) Vit D level was significantly lower than those of the control groups. In recent years, studies have shown that Hcy was associated with weakening of muscle functions 20,21. Cysteine is the mediator of a number of key metabolic processes, such as demethylation and antioxidation function in the cell.…”

Defective Homocysteine Metabolism: Potential Implications for Skeletal Muscle Malfunction

“…The disrupted Z-discs and disorganized banding pattern along with excessive collagen deposition in the basal lamina were observed in a patient with homocystinuria [5]. Chronic administration of homocysteine has been shown to reduce rat skeletal muscle cell viability and produce energy imbalance [6]. Abnormally higher levels of homocysteine in both plasma and cerebrospinal fluids were found to correlate with amyotrophic lateral sclerosis (ALS), a motor neuronal disease that causes muscle degeneration [7,8].…”