Amino acids, synthesis iron-catalyzed

PAH, a nonheme iron-containing enzyme, is a member of a larger BI Independent amino acid hydroxylase family. In addition to PAH, the enzyme family includes tyrosine hydroxylase and tryptophan hydroxylase. The enzymes in this family participate in critical metabolic steps and are tissue specific. PAH catabolizes excess dietary PA and synthesizes tyrosine. In adrenal and nervous tissue, tyrosine hydroxylase catalyzes the initial steps in the synthesis of dihydrox-yphenylalanine. In the brain, tryptophan is converted to 5-hydroxytryptophan as the first step of serotonin synthesis. Consequently, these enzymes are highly regulated not only by their expression in different tissues but also by reversible phosphorylation of a critical serine residue found in regulatory domains of the three enzymes. Since all three enzymes are phosphorylated and dephosphorylated by different kinases and phosphatases in response to the need for the different synthetic products, it is not unexpected that the exact regulatory signal for each member of the enzyme family is unique. 

Catabolism of tyrosine and tryptophan begins with oxygen-requiring steps. The tyrosine catabolic pathway, shown at the end of this chapter, results in the formation of fumaric acid and acetoaceticacid, Iryptophan catabolism commences with the reaction catalyzed by tryptophan-2,3-dioxygenase. This enzyme catalyzes conversion of the amino acid to N-formyl-kynurenine The enzyme requires iron and copper and thus is a metalloenzyme. The final products of the pathway are acetoacetyl-CoA, acetyl-Co A, formic add, four molecules of carbon dioxide, and two ammonium ions One of the intermediates of tryptophan catabolism, a-amino-P-carboxyrnuconic-6-semialdchydc, can be diverted from complete oxidation, and used for the synthesis of NAD (see Niacin in Chapter 9). 

Amidocarbonylation is a recently developed, organometallic-catalyzed route to amino acid generation - particularly A(-acyl a-amino acids - using either aldehydes or alkenes as starting materials and synthesis gas as an integral building block. The two principal classes of reaction are illustrated in eqs. (1) and (2). Both syntheses offer the opportunity to introduce two functionalities, amido and carboxylate, simultaneously where an amide is the co-reactant. Homogeneous amidocarbonylation catalysts are typically cobalt carbonyl-based, or utilize transition-metal binary systems, e. g. cobalt-rhodium, cobalt-palladium, and cobalt-iron. 

Tryptophan is an essential amino acid involved in synthesis of several important compounds. Nicotinic acid (amide), a vitamin required in the synthesis of NAD+ and NADP+, can be synthesized from tryptophan (Figure 17-24). About 60 mg of tryptophan can give rise to 1 mg of nicotinamide. The synthesis begins with conversion of tryptophan to N-formylkynurenine by tryptophan pyrrolase, an inducible iron-porphyrin enzyme of liver. N-Formylkynurenine is converted to kynurenine by removal of formate, which enters the one-carbon pool. Kynurenine is hydroxylated to 3-hydroxykynurenine, which is converted to 3-hydroxyanthranilate, catalyzed by kynureninase, a pyridoxal phosphate-dependent enzyme. 3-Hydroxyanthranilate is then converted by a series of reactions to nicotinamide ribotide, the immedi-... 

Not really. A system rich in amino acids would have at least some peptides. And there are many processes that are easily catalyzed by simple proteins but have never been demonstrated using RNA ribozymes. An example would be the sort of electron transfer mediated by iron sulfur clusters. Cellular synthesis of purines and pyrimidines must be very ancient, but it would seem likely that these are merely representatives of many other processes involving amino acids and peptides. 

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