Transaminations

Transamination reactions combine reversible amina-tion and deamination, and they mediate redistribution of amino groups among amino acids. Transaminases (aminotransferases) are widely distributed in human tissues and are particularly active in heart muscle, liver, skeletal muscle, and kidney. The general reaction of transamination is 

Keto acid Keto acid Amino acid 

The a-ketoglutarate/L-glutamate couple serves as an amino group acceptor/donor pair in transaminase reactions. The specificity of a particular transaminase is for the amino group other than the glutamate. Two transaminases whose activities in serum are indices of liver damage catalyze the following reactions  

Glutamate-pyruvate trar minase(GPT) or alanine aminotransferase (ALT) 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

Glutamic acid is the central product of reductive amination. Transamination from glutamic acid to a-keto acids leads to the formation of 

Demonstrating the existence of multiple transaminases in the late 1930s and early 1940s was very difficult. Chromatographic separation of amino acids was not available until the mid-1940s and paper chromatography was not in common use until 1948-1950 when Hird and Rowsell finally showed the existence of the wide range of transaminases and the universality of the transamination process. 

Work in the preceding 10 years had however been simplified by the development by P.P.Cohen of a new, specific micromethod for the estimation of glutamate, following a suggestion of Krebs. Glutamic acid specifically reacts with chloramine—T, an active form of hypochlorite, to give succinonitrile and carbon dioxide which could be measured manometrically. 

It was then possible to confirm the existence of two transaminating systems, the original one utilizing pyruvate as amino acceptor, and a second which used oxaloacetate. Both enzymes were purified and found to be very specific for their substrates. The reactions catalyzed were freely reversible. 

The biological importance of transamination was confirmed using 15N-labeling experiments (Tannenbaum and Shemin, 1950). 15N-leucine incubated with pig heart muscle gave highly labelled 15N-glutamate, evidence that leucine could be transaminated. Isotope experiments were then extended to the whole range of amino acids. 

Many pathways to natural products involve steps which remove portions of the carbon skeleton. Although two or more carbon atoms may be 

Decarboxylation of a-keto acids is a feature of primary metabolism, e.g. pyruvic acid - acetaldehyde in glycolysis, and pyruvic acid acetyl-CoA, an example of overall oxidative decarboxylation prior to entry of acetyl-CoA 

TPP anion O ii h3c h reverse aldol-type reaction, H enamine-imine y tautomerism N h3c. xoh H R. A. n Js 

Ffeifelder, Practical Catalytic Hydrogenation, Wiley Interscience, New York (1971), Chpt 16 M. Freifelder, Catalytic Hydrogenation in Organic Synthesis Procedures and Commentary, J. 

Wiley Sons, New York (1978), Chpt 10 Russ Chem Rev 49 14 (1980) 

Houben-Weyl, Methods of Organic Chemistry, 4th ed, Vol E21d, G. Thieme, Stuttgart-New York (1995), p 4199 (enantioselective) 

chiral Cp2Ti(BINAP)-n-BuLi-PhSiH3 H2, cat Ir-chiral bisphosphine (enantioselective) Hj, cat [Ir(diphosphine)Hl2]2 (enantioselective) H2, Raney nickel 

HOAc JACS 96 7812(1974) Org Prep Proc Int 17 317 (1985) (review) 

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L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

In transamination an amine group is transferred from L glutamic acid to pyruvic acid An outline of the mechanism of transamination is presented m Figure 27 4... 

FIGURE 27 4 The mecha nism of transamination All the steps are enzyme catalyzed... 

The reactions that amino acids undergo in living systems include transamination and decarboxylation... 

Transaminases Transamination Transannular peroxide Transcat process Transcobalamin II Transcortin... 

Suitable methods for linking a phosphoms—nitrogen bond to the ayiridine ring are the aminolysis of halogenated phosphoms compounds (2,280—282), the transamination of phosphoramines with excess a iridine (283), the reaction with phosphites (284) and phosphoramidites (285) which have a free OH group, or the reaction of phosphines with a iridines and carbon tetrachloride (286). 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

Fig. 3. (a) Reaction of pytidoxal 5 -phosphate (PLP) witii an amino-temiinal amino group of hemoglobin (Hb). The reagent is in the form of a Schiff s base with tris(hydroxymethyl)aminomethane [77-86-1] (Tris) buffet, and the reaction is a transamination, (b) The resulting unstable Schiff s base is reduced with... 

Phosphorus derivatives of different structures have been prepared including pyrazol-1-ylphosphines PPzs, PhPPz2 and Ph2PPz (Pz for pyrazolate anion (72CRV497,80MI40402)). By transamination with tris(dimethylamino)phosphine, pyrazoles and indazole are converted into (291) and (292), respectively (67CR(C)(265)1507). 3,5-Dimethylpyrazole reacts with amidodichlorophosphates to yield triamides (293) whereas 1-substituted pyrazolones yield amidophosphates (294) (71LA(750)39). 

Transamination of trifluoroacetylated vinyl ethers followed by monoacylation by diethyl malonate gives an intermediate that is cyclized to a trifluoromethylpyrid me derivative [9, 41] (equation 21)... 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

PEP carboxylase occurs in yeast, bacteria, and higher plants, but not in animals. The enzyme is specifically inhibited by aspartate, which is produced by transamination of oxaloacetate. Thus, organisms utilizing this enzyme control aspartate production by regulation of PEP carboxylase. Malic enzyme is found in the cytosol or mitochondria of many animal and plant ceils and is an NADPIT-dependent enzyme. 

Glyoxysomes do not contain all the enzymes needed to run the glyoxylate cycle succinate dehydrogenase, fumarase, and malate dehydrogenase are absent. Consequently, glyoxysomes must cooperate with mitochondria to run their cycle (Figure 20.31). Succinate travels from the glyoxysomes to the mitochondria, where it is converted to oxaloacetate. Transamination to aspartate follows... 

The second electron shuttle system, called the malate-aspartate shuttle, is shown in Figure 21.34. Oxaloacetate is reduced in the cytosol, acquiring the electrons of NADH (which is oxidized to NAD ). Malate is transported across the inner membrane, where it is reoxidized by malate dehydrogenase, converting NAD to NADH in the matrix. This mitochondrial NADH readily enters the electron transport chain. The oxaloacetate produced in this reaction cannot cross the inner membrane and must be transaminated to form aspartate, which can be transported across the membrane to the cytosolic side. Transamination in the cytosol recycles aspartate back to oxaloacetate. In contrast to the glycerol phosphate shuttle, the malate-aspartate cycle is reversible, and it operates as shown in Figure 21.34 only if the NADH/NAD ratio in the cytosol is higher than the ratio in the matrix. Because this shuttle produces NADH in the matrix, the full 2.5 ATPs per NADH are recovered. 

Compartmentation of these reactions to prevent photorespiration involves the interaction of two cell types, mescrphyll cells and bundle sheath cells. The meso-phyll cells take up COg at the leaf surface, where Og is abundant, and use it to carboxylate phosphoenolpyruvate to yield OAA in a reaction catalyzed by PEP carboxylase (Figure 22.30). This four-carbon dicarboxylic acid is then either reduced to malate by an NADPH-specific malate dehydrogenase or transaminated to give aspartate in the mesophyll cells. The 4-C COg carrier (malate or aspartate) then is transported to the bundle sheath cells, where it is decarboxylated to yield COg and a 3-C product. The COg is then fixed into organic carbon by the Calvin cycle localized within the bundle sheath cells, and the 3-C product is returned to the mesophyll cells, where it is reconverted to PEP in preparation to accept another COg (Figure 22.30). Plants that use the C-4 pathway are termed C4 plants, in contrast to those plants with the conventional pathway of COg uptake (C3 plants). 

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