Tyrosine Metabolism

Inherited disorders of tyrosine catabolism have been identified at five of the six enzymatic steps. Under normal conditions tyrosine concentrations are regulated by its synthetic enzyme (phenylalanine hydroxylase) and especially the first catabolic enzyme (tyrosine aminotransferase). Acquired or inherited deficiency of the second catabolic enzyme (4-hydroxyphenylpyruvate dioxygenase) also results in hypertyrosinemia. Tyrosine is mainly degraded in the liver but to a minor extent also in the kidney. In tyrosinemia type I, the primary defect is in the last enzyme of the pathway, accumulation of toxic metabolites are seen, and the hypertyrosinemia results from secondary deficiency of 4-hydroxyphenylpyruvate dioxygenase, which also is found in severe liver disease in general and in the immature liver. Generally, there is no common phenotype to the different disorders of tyrosine degradation. The occurrence of corneal and skin lesions, as seen in tyrosinemia type II, is a direct effect of high tissue tyrosine. Cognitive impairment is common in tyrosinemia type II, probably common in type III, and increasingly reported in type I. The liver and kidney diseases of tyrosinemia type I are caused by accumulation of toxic metabolites (fumarylacetoacetate and its derivatives) and can be prevented by an inhibitor (nitisinone) of tyrosine degradation at the level of 4-hydroxyphenylpyruvate dioxygenase. Whether maleylacetoacetate hydrolase that essentially gives the same metabolic features as tyrosinemia type I results in clinical features is unclear. In alkaptonuria there is no increase in tyrosine level, and the degradation of tyrosine proceeds at a normal rate to produce homogentisate. Upon oxidation, homogentisate forms reactive intermediates and pigment, which is deposited in various tissues particularly in joints and connective tissue. In hawkinsinuria, a very rare condition, data suggest that an aberrant metabolism of 4-hydroxyphenylpyruvate in some cases may lead to failure to thrive, acidosis, and excretion of a characteristic metabolite pattern.</p

Tyrosine Metabolism

Inherited disorders of tyrosine catabolism have been identified at five of the six enzymatic steps. Under normal conditions tyrosine concentrations are regulated by its synthetic enzyme (phenylalanine hydroxylase) and especially the first catabolic enzyme (tyrosine aminotransferase). Acquired or inherited deficiency of the second catabolic enzyme (4-hydroxyphenylpyruvate dioxygenase) also results in hypertyrosinemia. Tyrosine is mainly degraded in the liver but to a minor extent also in the kidney. In tyrosinemia type I, the primary defect is in the last enzyme of the pathway, accumulation of toxic metabolites are seen, and the hypertyrosinemia results from secondary deficiency of 4-hydroxyphenylpyruvate dioxygenase, which also is found in severe liver disease in general and in the immature liver. Generally, there is no common phenotype to the different disorders of tyrosine degradation. The occurrence of corneal and skin lesions, as seen in tyrosinemia type II, is a direct effect of high tissue tyrosine. Cognitive impairment is common in tyrosinemia type II, probably common in type III, and increasingly reported in type I. The liver and kidney diseases of tyrosinemia type I are caused by accumulation of toxic metabolites (fumarylacetoacetate and its derivatives) and can be prevented by an inhibitor (nitisinone) of tyrosine degradation at the level of 4-hydroxyphenylpyruvate dioxygenase. Whether maleylacetoacetate hydrolase that essentially gives the same metabolic features as tyrosinemia type I results in clinical features is unclear. In alkaptonuria there is no increase in tyrosine level, and the degradation of tyrosine proceeds at a normal rate to produce homogentisate. Upon oxidation, homogentisate forms reactive intermediates and pigment, which is deposited in various tissues particularly in joints and connective tissue. In hawkinsinuria, a very rare condition, data suggest that an aberrant metabolism of 4-hydroxyphenylpyruvate in some cases may lead to failure to thrive, acidosis, and excretion of a characteristic metabolite pattern.</p

Tyrosine Metabolism

Inherited disorders of tyrosine catabolism have been identified at five of the six enzymatic steps. Under normal conditions tyrosine concentrations are regulated by its synthetic enzyme (phenylalanine hydroxylase) and especially the first catabolic enzyme (tyrosine aminotransferase). Acquired or inherited deficiency of the second catabolic enzyme (4-hydroxyphenylpyruvate dioxygenase) also results in hypertyrosinemia. Tyrosine is mainly degraded in the liver but to a minor extent also in the kidney. In tyrosinemia type I, the primary defect is in the last enzyme of the pathway, accumulation of toxic metabolites are seen, and the hypertyrosinemia results from secondary deficiency of 4-hydroxyphenylpyruvate dioxygenase, which also is found in severe liver disease in general and in the immature liver. Generally, there is no common phenotype to the different disorders of tyrosine degradation. The occurrence of corneal and skin lesions, as seen in tyrosinemia type II, is a direct effect of high tissue tyrosine. Cognitive impairment is common in tyrosinemia type II, probably common in type III, and increasingly reported in type I. The liver and kidney diseases of tyrosinemia type I are caused by accumulation of toxic metabolites (fumarylacetoacetate and its derivatives) and can be prevented by an inhibitor (nitisinone) of tyrosine degradation at the level of 4-hydroxyphenylpyruvate dioxygenase. Whether maleylacetoacetate hydrolase that essentially gives the same metabolic features as tyrosinemia type I results in clinical features is unclear. In alkaptonuria there is no increase in tyrosine level, and the degradation of tyrosine proceeds at a normal rate to produce homogentisate. Upon oxidation, homogentisate forms reactive intermediates and pigment, which is deposited in various tissues particularly in joints and connective tissue. In hawkinsinuria, a very rare condition, data suggest that an aberrant metabolism of 4-hydroxyphenylpyruvate in some cases may lead to failure to thrive, acidosis, and excretion of a characteristic metabolite pattern.</p

Renal Mitochondrial Cytopathies

Renal diseases in mitochondrial cytopathies are a group of rare diseases that are characterized by frequent multisystemic involvement and extreme variability of phenotype. Most frequently patients present a tubular defect that is consistent with complete De Toni-Debré-Fanconi syndrome in most severe forms. More rarely, patients present with chronic tubulointerstitial nephritis, cystic renal diseases, or primary glomerular involvement. In recent years, two clearly defined entities, namely 3243 A > G tRNALEU mutations and coenzyme Q10 biosynthesis defects, have been described. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this paper, the physiopathologic bases of mitochondrial cytopathies, the diagnostic approaches, and main characteristics of related renal diseases are summarized

Tyrosine Metabolism

Inherited disorders of tyrosine catabolism have been identified at five of the six enzymatic steps. Under normal conditions tyrosine concentrations are regulated by its synthetic enzyme (phenylalanine hydroxylase) and especially the first catabolic enzyme (tyrosine aminotransferase). Acquired or inherited deficiency of the second catabolic enzyme (4-hydroxyphenylpyruvate dioxygenase) also results in hypertyrosinemia. Tyrosine is mainly degraded in the liver but to a minor extent also in the kidney. In tyrosinemia type I, the primary defect is in the last enzyme of the pathway, accumulation of toxic metabolites are seen, and the hypertyrosinemia results from secondary deficiency of 4-hydroxyphenylpyruvate dioxygenase, which also is found in severe liver disease in general and in the immature liver. Generally, there is no common phenotype to the different disorders of tyrosine degradation. The occurrence of corneal and skin lesions, as seen in tyrosinemia type II, is a direct effect of high tissue tyrosine. Cognitive impairment is common in tyrosinemia type II, probably common in type III, and increasingly reported in type I. The liver and kidney diseases of tyrosinemia type I are caused by accumulation of toxic metabolites (fumarylacetoacetate and its derivatives) and can be prevented by an inhibitor (nitisinone) of tyrosine degradation at the level of 4-hydroxyphenylpyruvate dioxygenase. Whether maleylacetoacetate hydrolase that essentially gives the same metabolic features as tyrosinemia type I results in clinical features is unclear. In alkaptonuria there is no increase in tyrosine level, and the degradation of tyrosine proceeds at a normal rate to produce homogentisate. Upon oxidation, homogentisate forms reactive intermediates and pigment, which is deposited in various tissues particularly in joints and connective tissue. In hawkinsinuria, a very rare condition, data suggest that an aberrant metabolism of 4-hydroxyphenylpyruvate in some cases may lead to failure to thrive, acidosis, and excretion of a characteristic metabolite pattern.</p

A discrete time relativistic Toda lattice

Four integrable symplectic maps approximating two Hamiltonian flows from the relativistic Toda hierarchy are introduced. They are demostrated to belong to the same hierarchy and to examplify the general scheme for symplectic maps on groups equiped with quadratic Poisson brackets. The initial value problem for the difference equations is solved in terms of a factorization problem in a group. Interpolating Hamiltonian flows are found for all the maps.Comment: 32 pages, LaTe