Tyrosine Metabolism

Francjan J. Van Spronsen, Alberto Burlina*, Carlo Dionisi Vici

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
70 Downloads (Pure)


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.

Originele taal-2English
TitelPhysician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Second Edition
UitgeverijSpringer International Publishing AG
Aantal pagina's12
ISBN van elektronische versie9783030721848
ISBN van geprinte versie9783030721831
StatusPublished - 2022


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