Catabolism aromatic amino acids

The synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

Serotonin is an indolamine neurotransmitter, derived from the amino acid L-tryptophan. Tryptophan is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase. 5-HTP is converted to 5-hydroxytryptamine (serotonin, 5-HT) by aromatic amino acid decarboxylase. In the pineal gland, 5-HT may be further converted to /V-acetyl serotonin by 5-HT /V-acetyltransferase and then to melatonin by 5-hyroxyindole-O-methyltransferase. 5-HT is catabolized by monoamine oxidase, and the primary end metabolite is 5-hydroxyindoleacetic acid (5-HIAA). 

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

One of the best characterized physiological functions of (6R)-tetrahydrobio-pterin (BH4, 43) is the action as a cofactor for aromatic amino acid hydroxylases (Scheme 28). There are three types of aromatic amino acid hydroxylases phenylalanine hydroxylase [PAH phenylalanine monooxygenase (EC 1.14.16.1)], tyrosine hydroxylase [TH tyrosine monooxygenase (EC 1.14.16.2)] and tryptophan hydroxylase [TPH tryptophan monooxygenase (EC 1.14.16.4)]. PAH converts L-phenylalanine (125) to L-tyrosine (126), a reaction important for the catabolism of excess phenylalanine taken from the diet. TH and TPH catalyze the first step in the biosyntheses of catecholamines and serotonin, respectively. Catecholamines, i.e., dopamine, noradrenaline and adrenaline, and serotonin, are important neurotransmitters and hormones. TH hydroxylates L-tyrosine (126) to form l-DOPA (3,4-dihydroxyphenylalanine, 127), and TPH catalyzes the hydroxylation of L-tryptophan (128) to 5-hydroxytryptophan (129). The hydroxylated products, 127 and 129, are decarboxylated by the action of aromatic amino acid decarboxylase to dopamine (130) and serotonin (131), respectively. 

Some catabolic reactions of amino acid carbon chains are easy transformations to and from TCA cycle intermediates—for example, the transamination of alanine to pyruvate. Reactions involving 1-carbon units, branched-chain, and aromatic amino acids are more complicated. This chapter starts with 1-carbon metabolism and then considers the catabolic and biosynthetic reactions of a few of the longer side chains. Amino acid metabolic pathways can present a bewildering amount of material to memorize. Perhaps fortunately, most of the more complicated pathways lie beyond the scope of an introductory course or a review such as this. Instead of a detailed listing of pathways, this chapter concentrates on general principles of amino acid metabolism, especially those that occur in more than one pathway. 

There is a great deal of evidence that deficiency of serotonin (5-hydroxytryptamine) is a factor in depressive illness, and many antidepressant drugs act to decrease its catabolism or enhance its interaction with receptors. A key enzyme involved in the synthesis of serotonin (and the catecholamines) is aromatic amino acid decarboxylase, which is pyridoxal phosphate-dependent. Therefore, it has been suggested that vitamin Be deficiency may result in reduced formation of the neurotransmitters and thus be a factor in the etiology of depression. Conversely, it has been suggested that supplements of vitamin Be may increase aromatic amino acid decarboxylase activity, and increase amine synthesis and have a mood-elevating or antidepressant effect. There is little evidence that vitamin Be deficiency affects the activity of aromatic amino acid decarboxylase. In patients with kidney failure, undergoing renal dialysis, the brain concentration of pyridoxal phosphate falls to about 50% of normal, with no effect on serotonin, catecholamines, or their metabolites (Perry etal., 1985). 

An increase in the aromatic amino acids phenylalanine and tyrosine occurs due to the lowered hepatic uptake of enterally released amino acids and their restricted catabolism in the liver. They are also released to a greater extent from the muscles in cases of cirrhosis with catabolism. Furthermore, phenylalanine hydroxylase... 

Arginine, 2D biosynthesis, 435 catabolism, 431 134 chemical structure, 20 plasma concentration, 465 Argininosuccinate lyase, 439 Acgininosuccinate synthase, 439 Aromatic amino acids, chemical structure, 19 Arsenate, 840 Artenosclcrosis, 357 Arteriovenous differences, 19 199 Artery, physiology, 359 Ascoitale... 

Tocopherols eind tocotrienols are importeint constituents of chloroplast membranes in green plants, tmd are tilso found in large amounts in seeds. The aromatic ring arises from homogentisic acid, which is both a precursor of aromatic amino acids and also tm intermediate in the catabolism of tyrosine. The side chain is formed by the addition of geranyl-geranyl pyrophosphate to yield initially 5-tocotrienol. Successive methylation of the ring results in the formation of and a-tocotrienols the tocopherols are formed by reduc-... 

The pathways involved in the catabolism of the individual amino acids range from one-step reactions, such as with aspartate, glutamate, and alanine, which use the appropriate amino transferases, to multistep pathways of the aromatic amino acids and lysine (e.g., tyrosine is degraded in four steps to acetoacetate and fumarate). 

Figure 5. The biocatalytic pathway (boxed arrows) created for microbial conversion of D-glucose into cis, cw-muconate from the perspective of the biochemical pathways from which the enzymes were recruited. Conversion of D-glucose into DHS requires transketolase (tkt) from the pentose phosphate pathway and DAHP synthase (aroF, aroG, aroH)y DHQ synthase aroB and DHQ dehydratase aroD) from the common pathway of aromatic amino acid biosynthesis. Conversion of DHS into catechol requires DHS dehydratase (aroZ, enzyme A) from hydroaromatic catabolism, protocatechuate decarboxylase aroY, enzyme B), and catechol 1,2-dioxygenase (caM, enzyme C) from the benzoate branch of the p-ketoadipate pathway. (Adapted and reproduced with permission from ref. 21.)...

A bifunctional dehydrogenase fromNeurospora which catalyzes the dehydrogenation of quinate and shikimate, functions in the inducible quinate catabolic pathway (Section IV). The catabolic form of the enzyme is distinguished from the form that occurs in the aggregate which is involved in the biosynthesis of the aromatic amino acids (Ahmed and Giles, 1969). 

General metabolic significance. Ascorbic acid participates in numerous biological events concerning electron transport reactions, hydroxylations, oxidative catabolism of aromatic amino acids one of the most important biologic redox systems (no coenzyme function). 

In the aromatic amino acid biosynthesis, chorismic acid (51) is converted into anthranilic acid, which would be a potential precursor providing both nitrogens for the ring as well as the aromatic system of phenazines. However, anthranilic acid and other proposed intermediates like quinic acid, tryptophan, tyrosine, and phenylalanine have been questioned on the basis of studies of mutants of phenazine producing organisms with blocked catabolism of these various possible intermediates. 

For the biosynthesis of cell components a microorganism must be supplied with appropriate low molecular weight compounds such as sugars, organic acids, amino acids etc. Many of 2-, 3-, 4- and 5-carbon compounds are formed in catabolic reactions. In propionic acid bacteria these reactions comprise the propionic acid fermentation, TCA cycle and hexose monophosphate shunt. The latter supplies the cell with erythrose-phosphate, ribose-5-phosphate and reducing equivalents (NADPH) needed for many syntheses. Erythrose-4-phosphate is used in the formation of aromatic amino acids phenylalanine, tryptophane, tyrosine. Ribose-5-phosphate is incorporated into nucleic acids. The pentose cycle and propionic acid fermentation, as mentioned before, have a number of common precursors and enzymes. The inclusion of common precursors into one or another pathway is regulated by the level of ATP (Labory, 1970), and this regulation in fact determines the ratio of catabolic and anabolic processes in the cell. 

Fig. 1.1. Biosynthesis and regeneration of tetrahydrobiopterin including possible metabolic defects and catabolism of phenylalanine. l.l=phenylalanine-4-hydroxylase (PAH) 1.2/1.6 = GTP cyclohydrolase I (GTPCH), 1.3 = 6-pyruvoyl-tetra-hydropterin synthase (PTPS), 1.4 = dihydropteridine reductase (DHPR), 1.5 = pterin-4a-carbinolamine dehydratase (PCD), 1.7 = sepiapterin reductase SR, carbonyl reductase (CR), aldose reductase (AR), dihydrofolate reductase (DHFR), aromatic amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), nitric oxide synthase (NOS). Pathological metabolites used as specific markers in the differential diagnosis are marked in squares. n.e.=non-enzymatic...

The aromatic amino acid L-phenylalanine (primary metabolite) is directed into the phe-nylpropanoid pathway leading to hydroxy-cinnamic acids, lignin and flavonoids by the activity of L-phenylalanine ammonia-lyase (PAL), which brings about its nonoxidative deamination yielding ammonia and tvans-cinnamic acid (Fig. 1). PAL is one of the most studied plant enzymes, and its crystal structure has recently been solved [2]. PAL is related to the histidine and tyrosine ammonia-lyases of amino acid catabolism. A class of bifunctional PALs found in monocotyle-donous plants and yeast can also deaminate tyrosine [3]. A single His residue is responsible for this switch in substrate preference [3, 4]. All three enzymes share a unique MIO (4-methylidene-imidazole-5-one) prosthetic group at the active site. This is formed auto-catalytically from the tripeptide Ala-Ser-Gly by cyclization and dehydration during a late... 

Several new classes of compounds have been discovered in lichens during this period. For example six diphenyl ethers have been isolated and it would appear that they may arise biogenetically either by catabolism of the more common depsidones or by direct phenolic oxidation resulting in carbon-oxygen coupling of the mononuclear aromatic units [e.g. in leprolomin 118)]. A novel group of nonacyclic diketopiperazines have been isolated 14) and it would appear that these compounds are derived biogenetically from the aromatic amino-acid, tyrosine. 

In liver failure the plasma concentrations of the aromatic amino acids (AAAs) tyrosine, phenylalanine, and tryptophan increase, probably because they are predominantly broken down in the liver, whereas the plasma levels of BCAAs decrease while they are degraded in excess in muscle as a consequence of hepatic failure-induced catabolism. As AAAs and BCAAs are all neutral amino acids and share a common transporter across the blood-brain barrier (system L carrier), changes in their plasma ratio are reflected in the brain, subsequently disrupting the neurotransmitter profile of the catecholamines and indoleamines (see sections on tyrosine and tryptophan). It has been hypothesized that this disturbance contributes to the multifactorial pathogenesis of hepatic encephalopathy. In line with this hypothesis it has been suggested that normalization of the amino acid pattern by supplementing extra BCAAs counteracts hepatic encephalopathy. 

Another subgroup of the 2His-lcarboxylate family is dependent on a reduced pterin cofactor (5). They catalyze hydrox-ylations at the aromatic positions of amino acids in phenylalanine catabolism and hormone biosynthesis (Fig. 2). Unlike the a-KG-dependent enzymes, the pterin co-substrate does not ligate to the iron directly. In the reaction cycle, the pterin cosubstrate supplies two electrons for the heteiolysis of O2 to give a yet to be characterized iron-oxygen hydroxylating species. 

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