Tyrosine aminotransferase deficiency

Fig. 16.17 Chromatogram of organic acids extracted using DEAE-Sephadex from the urine of a patient with tyrosine aminotransferase deficiency originally described by Kennaway and Buist (1971). Separated on their ethoxime and trimethylsilyl derivatives on 10 per cent OV-101 on HP Chromosorb W (80-100 mesh) using temperature programming from 110°C to 285 C at 4°C min" with a 5 min initial isothermal delay. Peak identifications are 1, sulphate 2, phosphate 3, tetronates 4, 4-hydroxyphenyl-acetate 5, aconitate plus homovanillate 6, hippurate 7, citrate 8, 4-hydroxyphenyl-lactate 9, 4-hydroxyphenylpyruvate 10, N-acetyltyrosine 11, -tetracosane (standard) 12, w-hexacosane (standard). (The horizontal axis represents the time elapsed in minutes from sample injection.)...

Kennaway, N.G. and Buist, N.R.M. (1971), Metabolic studies in a patient with hepatic cytosol tyrosine aminotransferase deficiency. Pediatr. Res., 5,287. 

Hepatic cytosolic tyrosine aminotransferase (tyrosine transaminase) deficiency produces tyrosinemia type II, an autosomal recessive trait marked by hypertyrosine-mia and tyrosinuria. Clinical manifestations may include corneal erosions and plaques, inflammation (from intracellular crystallization of tyrosine), and mental retardation. Low-tyrosine and low-phenylalanine diets are beneficial. 

Other types of tyrosinemia are related to specific enzyme defects (see Fig. 39.17). Tyrosinemia II is caused by a genetic deficiency of tyrosine aminotransferase (TAT) and may lead to lesions of the eye and skin as well as neurologic problems. Patients are treated with a low-tyrosine, low-phenylalanine diet. 

Hereditary tyrosinaemia type II is caused by a deficiency of tyrosine aminotransferase, leading to eye lesions, skin lesions and neurological complications. The aim of dietary management is to prevent the accumulation of tyrosine and phenylalanine by a low-protein diet. The protein requirements are met by supplementing the diet with a tyrosine- and phenylalanine-free amino acid mixture. 

In rats fed a diet adequate in vitamin Bg, the fraction of total pyridoxal phosphate found in the nuclei of liver cells was 21%, and this increased to 39% in rats fed a vitamin Bg-deflcient diet, indicating a conservation of the vitamin in the nuclear compartment during deficiency. Pyridoxal phosphate in the cell nucleus is protein bound, and this protein has an apparent molecular mass of 50 to 55 kDa. Cells grown in the presence of 5 mM pyridoxine have a decreased glucocorticoid-dependent induction of enzymes such as tyrosine aminotransferase. Vitamin Bg regulates transcriptional activation of human glucocorticoid receptors in the HeLa cells. The modulatory role in transcription is not restricted to the glucocorticoid receptor but extends to other members of the steroid hormone super family. The intracellular concentration of PLP could have a profound influence on steroid hormone-induced... 

---