Citrulline malate

CFS patients and is related to autonomic dysfunction. In a separate rat study, Giannesini et al. used citrulline malate (CM) to treat asthenia and found that the supplementation prevented the basal PCr/ATP ratio reduction and normalized the pHi time-course during muscular activ-ity. They conclude that CM supplementation corrects the impaired control of oxidative function and has protective effect on basal energy metabolism. The data from either human or animal studies provide a potential approach to therapy. 

Briand, J., Blehaut, H., Calvayrac, R., Laval-Martin, D. Use of a microbial model for the determination of drug effects on cell metabolism and energetics study of citrulline-malate. Biopharm. Drug Dispos. 1992,13 1-22. 

The effects of oral ingestion of citrulline malate on the bioenergetics and mechanical performance of muscle in the normal rat have been investigated with P MRS. Supplementation with citrulline malate did not affect the ratio of phosphocreatine/ATP (PCr/ATP), the concentration of phos-phorylated metabolites or intracellular pH at rest. During the stimulation, it lead to a 23% enhancement of specific force production, but had no effect on the time-courses of phosphorylated metabolites or intracellular pH. 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

The uiea cycle may be considered to be a mitochondrial pathway, as carbamyl phosphate synthase and ornithine transcarbamylase are mitochondrial enzymes however, the enzymes catalyzing subsequent steps of the pathway arc cytosolic-The steps leading to conversion of citrulline to ornithine occur in the cytosol. Hence, the pathway is shared by the mitochondrial and cytosolic compartments. The fumarate produced by the urea cycle is converted to malate by a cytoplasmic form of fumarase. Mittxihondrial fumarase is part of the Krebs cycle. Cytoplasmic malate can enter the mitochondrion by means of a transport system, such as the malate/phosphate exchanger or the ma ate/a-ketoglutaratc exchanger. These transport systems are membrane-bound proteins. 

The urea cycle converts NH4 to urea, a less toxic molecule. The sources of the atoms in urea are shown in color. Cit-rulline is transported across the inner membrane by a carrier for neutral amino acids. Ornithine is transported in exchange for H+ or citrulline. Fumarate is transported back into the mitochondrial matrix (for reconversion to malate) by carriers for a-ketoglutarate or tricarboxylic acids. 

Abbreviations Pj, phosphate pyr, pyruvate acylcam, acylcamitine cam, carnitine mal, malate cit, citrate isoc, isocitrate PEP, pho hoenolpyravate o-OG, a-oxoglutarate glu, glutamate asp, aspartate gin, glutamine orn, ornithine citrull, citrulline. 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

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