Tyrosine metabolism and related disorders : Medical Biochemistry : Dr Priyansh Jain

📌 𝐅𝐨𝐥𝐥𝐨𝐰 𝐨𝐧 𝐈𝐧𝐬𝐭𝐚𝐠𝐫𝐚𝐦:-   / drgbhanuprakash  

Tyrosine is an aromatic amino acid important in the synthesis of thyroid hormones, catecholamines, and melanin. Impaired catabolism of tyrosine is a feature of several acquired and genetic disorders that may result in elevated plasma tyrosine concentrations

Four autosomal-recessive disorders result from deficiencies in specific enzymes in the tyrosine catabolic pathway: hereditary tyrosinemia (HT) types 1, 2, and 3 and alkaptonuria (AKU). Except for AKU, these disorders result in elevated blood tyrosine levels.

Hypertyrosinemia is caused by a variety of genetic and acquired disorders. Acquired disorders are more common

HT1 (hepatorenal tyrosinemia) is characterized by severe, progressive liver disease and renal tubular dysfunction. Most patients present in early infancy with failure to thrive and hepatomegaly. Nitisinone is the medical treatment of choice.

HT2 (oculocutaneous tyrosinemia) is characterized by early development of eye and skin abnormalities that usually become apparent in the first year of life. HT2 should be suspected in patients with typical signs or elevated tyrosine levels on newborn metabolic screening. Management consists of a diet low in tyrosine and phenylalanine.

HT3 is a rare disorder. Affected patients often have neurologic dysfunction (ataxia, seizures, mild psychomotor retardation) but no other systemic involvement. Treatment consists of a diet low in tyrosine and phenylalanine.

AKU should be suspected in patients whose urine appears normal when fresh but turns dark brown or black if left standing after alkalinization. Patients with AKU usually are asymptomatic in childhood. During the third decade, deposits of brownish or bluish pigment become apparent in the ear cartilage and sclerae. Tyrosine levels are normal. No approved therapy is available. Dietary restriction of tyrosine and phenylalanine reduce the excretion of homogentisic acid (HGA), although the clinical effect is limited. Clinical trials with nitisinone are ongoing and have shown promise.

Transient tyrosinemia of the newborn is the most common acquired cause of hypertyrosinemia. It is caused by immaturity of 4-OH phenylpyruvate dioxygenase (HPD) and occurs in approximately 10 percent of preterm infants and in some term infants.

Hepatocellular dysfunction of any etiology can result in elevated plasma tyrosine levels and excretion of increased amounts of tyrosine metabolites in urine. The tyrosine levels usually are less than 500 micromol/L.

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