Tyrosine metabolic fate

Figure 30-12. Intermediates in tyrosine catabolism. Carbons are numbered to emphasize their ultimate fate. (a-KG, a-ketoglutarate Glu, glutamate PLP, pyridoxal phosphate.) Circled numerals represent the probable sites of the metabolic defects in type II tyrosinemia neonatal tyrosinemia alkaptonuria and 0 type I tyrosinemia, or tyrosinosis.

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

Phenylketonuria is perhaps the best known of the diseases of amino acid metabolism. Phenylketonuria is caused by an absence or deficiency of phenylalanine hydroxylase or, more rarely, of its tetrahydrobiopterin cofactor. Phenylalanine accumulates in all body fluids because it cannot be converted into tyrosine. Normally, three-quarters of the phenylalanine is converted into tyrosine, and the other quarter becomes incorporated into proteins. Because the major outflow pathway is blocked in phenylketonuria, the blood level of phenylalanine is typically at least 20-fold as high as in normal people. Minor fates of phenylalanine in normal people, such as the formation of phenylpyruvate, become major fates in phenylketonurics. 

Fates of tyrosine. Tyrosine can be degraded by oxidative processes to ace-toacetate and fumarate which enter the energy generating pathways of the citric acid cycle to produce ATP as indicated in Figure 38-2. Tyrosine can be further metabolized to produce various neurotransmitters such as dopamine, epinephrine, and norepinephrine. Hydroxylation of tyrosine by tyrosine hydroxylase produces dihydroxyphenylalanine (DORA). This enzyme, like phenylalanine hydroxylase, requires molecular oxygen and telrahydrobiopterin. As is the case for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to perturbations in dihydropteridine reductase or the biopterin synthesis pathway, anyone of which could lead to interruption of tyrosine hydroxylation, an increase in tyrosine levels, and an increase in transamination of tyrosine to form its cognate a-keto acid, para-hydroxyphenylpyruvate, which also would appear in urine as a contributor to phenylketonuria. 

In discussing iodide metabolism, we need only be concerned with the fate of inorganic iodides because organic iodides (tyrosine derivatives) are absorbed and enter the normal plasma pool of organic iodides produced by the thyroid. The site and the mechanism of absorption of organic iodides in the intestine are not exactly known, but somehow the dietary iodine is transported from the intestinal lumen into the blood. 

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