l-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity. Additionally, Arg or l-citrulline may provide novel and effective therapies for obesity, diabetes, and the metabolic syndrome. The effect of Arg in treating many developmental and health problems is unique among AAs, and offers great promise for improved health and wellbeing of humans and animals.

Arginine metabolism and nutrition in growth, health and disease

Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients

Although it is self-evident that the study of human nutrition has as its goal the optimal nutrition of man, the nutritional status of the body best suited to optimal performance, i.e., optimal nutrition, has unfortunately not yet been satisfactorily defined. Body composition of animals may be measured by direct chemical analysis and correlated with dietary intake and with the various aspects of performance; studies of body composition of living man, on the other hand, must rely on indirect measure ments. The following two reports, which give an account of the current status of the attack on the difficult task of measuring body composition in living man, are sponsored by the Committee on Nutrition to call attention to the resurgence of effort in this field during recent years. A fuller knowledge of the gross composition of the human body and its relation to preceding diet will constitute a significant step towards realization of the ultimate goal of nutritional science. Even then, a particular body composition will be of importance primarily in terms of functional performance. The availability of newer techniques should do much to stimulate physicians and nutritionists in defining body composition as an essential step in arriving at a more exact definition of optimal nutrition.

https://pediatrics.aappublications.org/content/pediatrics/29/3/476.full.pdf

Human body composition

Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.

Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene

The mitochondrial cytopathies are a heterogeneous group of diseases associated with defects in mitochondrial ATP production that affect the brain, skeletal muscle, heart, kidney, and liver. Mitochondria produce ATP by oxidative phosphorylation (OXPHOS). OXPHOS involves approximately 100 polypeptides, most of which are encoded in the Mendelian-inherited nuclear genes, but 13 of which are encoded in the maternally-inherited mitochondrial DNA (mtDNA).

Oxidative phosphorylation diseases. Disorders of two genomes.

A 2-week-old boy had profound generalized weakness, hypotonia, hyporeflexia, macroglossia, and severe lactic acidosis. The infant improved spontaneously: he held his head at 4 1/2 months, rolled over at 7 months, and walked by 16 months. At 33 months of age, he had mild proximal weakness. Macroglossia disappeared by age 4 months. Blood lactic acid declined steadily and was normal by 14 months of age. Histochemical and ultrastructural studies of muscle biopsy specimens obtained at 1 and 7 months of age showed excessive mitochondria, lipid, and glycogen; a third biopsy at age 36 months showed only atrophy of scattered fibers. Cytochrome c oxidase stain was positive in fewer than 5% of fibers in the first biopsy, in approximately 60% of fibers in the second biopsy, and in all fibers in the third biopsy. Biochemical analysis showed an isolated defect of cytochrome c oxidase activity, which was only 8% of the lowest control level in the first biopsy; the activity increased to 47% in the second biopsy and was higher than normal in the third. In contrast to that in the fatal infantile form of cytochrome c oxidase deficiency, the enzyme defect in this condition is reversible. The biochemical basis for this difference remains to be explained.

Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency.

A 2‐week‐old boy had profound generalized weakness, hypotonia, hyporeflexia, macroglossia, and severe lactic acidosis. The infant improved spontaneously: he held his head at 4 1/2 months, rolled over at 7 months, and walked by 16 months. At 33 month of age, he had mild proximal weakness. Macroglossia disappeared by age 4 months. Blood lactic acid declined steadily and was normal by 14 months of age. Histochemical and ultrastructural studies of muscle biopsy specimens obtained at 1 and 7 months of age showed excessive mitochondria, lipid, and glycogen; a third biopsy at age 36 months showed only atrophy of scattered fibers. Cytochrome c oxidase stain was positive in fewer than 5% of fibers in the first biopsy, in approximately 60% of fibers in the second biopsy, and in all fibers in the third biopsy. Biochemical analysis showed an isolated defect of cytochrome c oxidase activity, which was only 8% of the lowest control level in the first biopsy; the activity increased to 47% in the second biopsy and was higher than normal in the third. In contrast to that in the fatal infantile form of cytochrome c oxidase deficiency, the enzyme defect in this condition is reversible. The biochemical basis for this difference remains to be explained.

John F. Nicholson

Papers

Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency.

Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency.

Reference ranges for laboratory tests and procedures

Hyperammonemia resulting from intravenous alimentation using a mixture of synthetic l-amino acids: a preliminary report.

A controlled trial of glucose versus glucose and amino acids in premature infants.