Pathogenesis of Reye's Syndrome: A Working Hypothesis

PEDIATRICS ◽  
1975 ◽  
Vol 56 (6) ◽  
pp. 1081-1084
Author(s):  
M. Michael Thaler
Keyword(s):  
Fatty Liver ◽  
Intracellular Transport ◽  
Urea Cycle ◽  
Transport Mechanisms ◽  
Reye's Syndrome ◽  
Specific Therapy ◽  
Ammonia Metabolism ◽  
History Of ◽  
Urea Cycle Enzymes

The brief history of Reye's syndrome has been one of progressive familiarity with a deepening mystery. It is possible that the syndrome reflects a variety of etiologically unrelated conditions with similar clinicopathological manifestations. In this view, subclinical defects in ammonia metabolism may constitute a distinct, identifiable group among disorders responsible for encephalopathy with fatty liver. Awareness of the possible role of mutant urea cycle enzymes and deficient substrates in the pathogenesis of this important illness should stimulate investigations of enzyme kinetics and intracellular transport mechanisms which may reveal a spectrum of abnonmalities in ammonia metabolism-and a specific therapy for each.

Hepatic ammonia metabolism in a uricotelic treefrog Phyllomedusa sauvagei

1984 ◽  
Vol 246 (5) ◽  
pp. R805-R810 ◽  
Author(s):  
J. W. Campbell ◽  
J. E. Vorhaben ◽  
D. D. Smith
Keyword(s):  
Uric Acid ◽  
Urea Cycle ◽  
Liver Mitochondria ◽  
Synthetase Activity ◽  
Mitochondrial Enzyme ◽  
Ammonia Metabolism ◽  
Carbamoylphosphate Synthetase ◽  
High Degree ◽  
Isolated Liver ◽  
Urea Cycle Enzymes

Glutamine synthetase, a mitochondrial enzyme in liver of uricotelic reptiles and birds, is present in the cytosolic compartment of Phyllomedusa sauvagei liver. The average level is sufficient to account for the rate of uric acid excretion by adult frogs but is far lower than that present in birds and reptiles. Except for lower carbamoylphosphate synthetase activity, the activities of the urea cycle enzymes in P. sauvagei liver are comparable with those in adult ureotelic amphibians. The subcellular distribution of the urea cycle enzymes is much the same as in ureotelic amphibians and mammals with the possible exception of the occurrence of a small percentage of the carbamoylphosphate synthetase and ornithine transacarbamylase activities in the cytosol. In keeping with the subcellular localization of the enzymes, citrulline, and not glutamine, is formed by isolated liver mitochondria. The rapid degradation of glutamine by these mitochondria suggests a high degree of compartmentation of glutamine in the cytosol of P. sauvagei if it is to function as a precursor of uric acid in this compartment.

Aflatoxin B1 acute effects on three hepatic urea cycle enzymes using semiautomated methods: A model for Reye's syndrome

1980 ◽  
Vol 53 (2) ◽  
pp. 293-298 ◽  
Author(s):  
Peter M. Thurlow ◽  
Robert K. Desai ◽  
Paul M. Newberne ◽  
Henry Brown
Keyword(s):  
Aflatoxin B1 ◽  
Urea Cycle ◽  
Acute Effects ◽  
Reye's Syndrome ◽  
Urea Cycle Enzymes

scholarly journals Role of Bioflavonoid Quercetin on Expression of Urea Cycle Enzymes, Astrocytic and Inflammatory Markers in Hyperammonemic Rats

2016 ◽  
Vol 32 (1) ◽  
pp. 68-73 ◽  
Author(s):  
Sivamani Kanimozhi ◽  
Perumal Subramanian ◽  
Sakkaravarthy Shanmugapriya ◽  
Subramanian Sathishkumar
Keyword(s):  
Inflammatory Markers ◽  
Urea Cycle ◽  
Urea Cycle Enzymes

scholarly journals UREA CYCLE ENZYMES AND OROTIC ACID (OA) IN REYE'S SYNDROME (RS)

1977 ◽  
Vol 11 (4) ◽  
pp. 522-522 ◽  
Author(s):  
M Michael Thaler ◽  
Barry Beidarman
Keyword(s):  
Orotic Acid ◽  
Urea Cycle ◽  
Reye's Syndrome ◽  
Urea Cycle Enzymes

scholarly journals Role of dexamethasone and insulin on the development of the five urea-cycle enzymes in cultured rat foetal hepatocytes

1985 ◽  
Vol 225 (1) ◽  
pp. 271-274 ◽  
Author(s):  
A Husson ◽  
M Bouazza ◽  
C Buquet ◽  
R Vaillant
Keyword(s):  
Urea Cycle ◽  
Carbamoyl Phosphate Synthetase ◽  
Argininosuccinate Synthetase ◽  
Carbamoyl Phosphate ◽  
Urea Cycle Enzymes

The activity changes of the urea-cycle enzymes were monitored in cultured foetal hepatocytes after dexamethasone and insulin treatments. Addition of dexamethasone induced the development of carbamoyl-phosphate synthetase, argininosuccinate synthetase, argininosuccinase and arginase activities as soon as day 16.5 of gestation. When insulin was added together with dexamethasone, it markedly inhibited the steroid-induced increase in carbamoyl-phosphate synthetase, argininosuccinate synthetase and argininosuccinase activities.

Varicella Hepatitis and Reye's Syndrome: An Interrelationship?

PEDIATRICS ◽  
1977 ◽  
Vol 60 (5) ◽  
pp. 746-748
Author(s):  
Stephen E. Landay
Keyword(s):  
Significant Role ◽  
Urea Cycle ◽  
Intimate Relationship ◽  
Ammonia Level ◽  
Host Factors ◽  
Reye's Syndrome ◽  
Inborn Errors ◽  
Clinical Support ◽  
The Brain ◽  
Urea Cycle Enzymes

The host factors that may be important in the evolution of Reye's syndrome still need clarification. Thaler1,2 has raised the possibility that inborn errors in urea cycle enzymes may be instrumental in the development of the syndrome. He has postulated that such errors may lead to the hyperammonemia that is characteristic early in the illness. This elevated ammonia level may have a significant role in the pathogenesis of Reye's syndrome by virtue of its toxic effects on the brain, liver, and other organs. Cited below are three cases that occurred in one Florida community within one month. These may offer clinical support of the Thaler hypothesis, and they may illustrate an intimate relationship between Reye's syndrome and a less-discussed entity, varicella hepatitis.

scholarly journals Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

2015 ◽  
Vol 112 (17) ◽  
pp. 5521-5526 ◽  
Author(s):  
Natalia Qvartskhava ◽  
Philipp A. Lang ◽  
Boris Görg ◽  
Vitaly I. Pozdeev ◽  
Marina Pascual Ortiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Urea Cycle ◽  
Fear Memory ◽  
Whole Body ◽  
Chronic Liver Failure ◽  
Ammonia Metabolism ◽  
Cerebral Dysfunction ◽  
Deficient Mice

Urea cycle defects and acute or chronic liver failure are linked to systemic hyperammonemia and often result in cerebral dysfunction and encephalopathy. Although an important role of the liver in ammonia metabolism is widely accepted, the role of ammonia metabolizing pathways in the liver for maintenance of whole-body ammonia homeostasis in vivo remains ill-defined. Here, we show by generation of liver-specific Gln synthetase (GS)-deficient mice that GS in the liver is critically involved in systemic ammonia homeostasis in vivo. Hepatic deletion of GS triggered systemic hyperammonemia, which was associated with cerebral oxidative stress as indicated by increased levels of oxidized RNA and enhanced protein Tyr nitration. Liver-specific GS-deficient mice showed increased locomotion, impaired fear memory, and a slightly reduced life span. In conclusion, the present observations highlight the importance of hepatic GS for maintenance of ammonia homeostasis and establish the liver-specific GS KO mouse as a model with which to study effects of chronic hyperammonemia.

Sign in / Sign up

Export Citation Format

Share Document