Biochemical Investigations of Hyperammonæmia

Levin, B.; Oberholzer, V. G.; Sinclair, Lynne

doi:10.1016/s0140-6736(69)91419-6

Cited by 75 publications

(16 citation statements)

References 13 publications

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“…The binding of amino groups by pyruvate to form alanine thus serves to limit the extent to which ammonia production and accumulation are stimulated by exercise. The importance of this carrier function of alanine in nitrogen ,Mole, P. A., K metabolism is further indicated by the specific elevation of plasma alanine in a variety of hyperammonemic situations in which ammonia disposal is retarded (32), particularly as a consequence of abnormalities involving urea cycle enzymes (33)(34)(35). In addition, alanine serves as an intrahepatic ammonia-binding agent when urea synthesis ceases in the anoxic liver (36).…”

Section: Resultsmentioning

confidence: 99%

Amino acid metabolism in exercising man

Felig¹,

Wahren²

1971

J. Clin. Invest.

406

189

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A B S T R A C T Arterial concentration and net exchange across the leg and splanchnic bed of 19 amino acids were determined in healthy, postabsorptive subjects in the resting state and after 10 and 40 min of exercise on a bicycle ergometer at work intensities of 400, 800, and 1200 kg-m/min. Arterio-portal venous differences were measured in five subjects undergoing elective cholecystectomy.In the resting state significant net release from the leg was noted for 13 amino acids, and significant splanchnic uptake was observed for 10 amino acids. Peripheral release and splanchnic uptake of alanine exceeded that of all other amino acids, accounting for 35-40% of total net amino acid exchange. Alanine and other amino acids were released in small amounts (relative to net splanchnic uptake) by the extrahepatic splanchnic tissues drained by the portal vein.During exercise arterial ananine rose 20-25% with mild exertion and 60-96% at the heavier work loads.Both at rest and during exercise a direct correlation was observed between arterial alanine and arterial pyruvate levels. Net amino acid release across the exercising leg was consistently observed at all levels of work intensity only for alanine. Estimated leg alanine output increased above resting levels in proportion to the work load. Splanchnic alanine uptake during exercise exceeded that of all other amino acids and increased by 15-20% during mild and moderate exercise, primarily as a consequence of augmented fractional extraction of alanine. For all other amino acids, there was no change in arterial concentration during mild exercise. At heavier work loads, increases of 8-35% were noted for isoleucine, leucine, methionine, tyrosine, and phenylalanine, which were atThis work was presented in part at the 62nd Annual

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Section: Resultsmentioning

confidence: 99%

Amino acid metabolism in exercising man

Felig¹,

Wahren²

1971

J. Clin. Invest.

406

189

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“…T h e clinical course and pedigree of this patient are similar to that of other male patients with this genetic lesion [5,12,18,24,261, and substantiate the X-linked dominant transmission of the defect with varying degrees of illness in females. T h e pathogenesis of the disorder has been discussed extensively in previous reviews [5,6,15,25,291.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and Genetic Studies of a Family with Ornithine Transcarbamylase Deficiency

et al. 1974

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ExtractW e have described a patient with ornithine transcarbamylase (OTC) deficiency.T h e clinical course and pedigree substantiate the X-linked transmission of the defect with varying degrees of illness in females. Because orotic aciduria accompanied hyperammonemia in the patient, orotic acid was measured as an indication of a partial OTC deficiency after ammonia and protein loading in members of the patient's family. Both the mother, a n obligate carrier, and an aunt, the only symptomatic female in this pedigree, had hyperammonemia after the ingestion of ammonium chloride. They also had significant orotic aciduria after a protein load as did the two female cousins whose ammonium tolerance was normal. T h e maternal grandmother excreted a large amount of orotic acid in her urine relatively consistently. 'These data suggest that the two female cousins and the maternal grandmother are asymptomatic female heterozygotes despite their normal ammonium loading tests. SpeculationProtein loading in the form of a relatively palatable and innocuous meal, followed by determination of orotic acid content in urine, may prove to be a sensitive, noninvasive, and easy means to identify female carriers of ornithine transcarbamylase deficiency.

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“…This finding was originally interpreted [5] as evidence of a defect in the direct incorporation of the nitrogen of ingested ammonia into urea, with consequent incorporation of abnormally large amounts of ammonium nitrogen into the pool of amino acids (presumably largely glutamine), giving rise to ammonia in the urine. This interpretation seems reasonable, particularly in view of the finding by Levin and co-workers [10] that glutamine is increased in both plasma and urine in patients with deficient hepatic ornithine transcarbamylase. However, in our patient, JS, glutamine in the plasma was not consistently elevated, nor was there any evidence of consistently elevated glutamine in the urine.…”

Section: Incorporation Of 15 N From Ingested ^Nh^cl Into Glycinementioning

confidence: 71%

“…The latter show mild to severe hyperammonemia over a period of years, and have levels of hepatic ornithine transcarbamylase which are readily detectable but generally less than 10% of normal (cf. [10]). (Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., and Nuzum, C. T.: Complete ornithine transcarbamylase deficiency: a cause of lethal hyperammonemia (Abstract).…”

Section: Addendummentioning

confidence: 99%