Transamination oxidative

Additional metabolism, involving side-chain degradation, proceeds by transamination, oxidative deamination, and decarboxylation to yield thyroacetic acid and thyroethanediol cleavage of the diphenyl ether linkage has been detected as well, both in vitro and in vivo. The reactions through which thyroid hormone is metabolized are summarized in Figure 34.5. 

It has been demonstrated that Cu(II) and Fe(III) can also greatly accelerate the rate of reaction and actual chelate intermediates have been isolated. In model systems, all reactions catalyzed by enzymes except decarboxylation have been reproduced transamination, oxidative deamination, elimination of jS- and y-substituents, etc. Many substitutes for pyridoxal have been synthesized and examined in the biological system. The following compounds were observed to be ineffective ... 

Describe the reactions of transamination, oxidative deamination, and the entry of amino acid carbons into the citric acid cycle. 

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. 

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. 

Succinic semialdehyde (SSA) is synthesized in the mitochondria through transamination of y-aminobutyric acid (GABA) by GABA transaminase (GABA-T). Most of the SSA is oxidized by SSA dehydrogenase (SSA-DH) to form succinate, which is used for energy metabolism and results in the end products CO2 + H2O, which are expired. A small portion of SSA (<2%) is converted by SSA reductase (SSA-R) in the cytosol to GHB. GHB may also be oxidized back to SSA by GHB dehydrogenase (GHB-DH). 

The amino acids are required for protein synthesis. Some must be supplied in the diet (the essential amino acids) since they cannot be synthesized in the body. The remainder are nonessential amino acids that are supplied in the diet but can be formed from metabolic intermediates by transamination, using the amino nitrogen from other amino acids. After deamination, amino nitrogen is excreted as urea, and the carbon skeletons that remain after transamination (1) are oxidized to CO2 via the citric acid cycle, (2) form glucose (gluconeogenesis), or (3) form ketone bodies. 

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

Serine. Oxidation of the a-hydroxyl group of the glycolytic intermediate 3-phosphoglycerate converts it to an 0x0 acid, whose subsequent transamination and dephosphorylation leads to serine (Figure 28—5). 

Urea biosynthesis occurs in four stages (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2). 

The anaerobic metabolism of L-phenylalanine by Thauera aromatica under denitrifying conditions involves several steps that result in the formation of benzoyl-CoA (a) conversion to the CoA-ester by a ligase, (b) transamination to phenylacetyl-CoA, (c) a-oxidation to phenylglyoxalate, and (d) decarboxylation to benzoyl-CoA (Schneider et al. 1997). 

In Pseudomonas fluorescens ATCC 29574, oxidation produced a number of C2-metabo-lites after initial transamination (Figure 10.3b) (Narumiya et al. 1979). 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Try to acetyl-CoA via ring oxidation and cleavage to ketoadipate Lys to acetyl-CoA via transamination and deamination to ketoadipate... 

Additionally, several amino acids may undergo transamination to produce glutamate which in the liver is oxidatively deaminated to form 2-oxoglutarate (2-OG, see Figure 6.6), a substrate of the TCA cycle. Alternatively, glutamate maybe converted into glutamine, an important but often overlooked fuel substrate. 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

In a muscle at rest, most of the 2-oxo acids produced from transamination of branched chain amino acids are transported to the liver and become subject to oxidation in reactions catalysed by branched-chain 2-oxo acid dehydrogenase complex. During periods of exercise, however, the skeletal muscle itself is able to utilize the oxo-acids by conversion into either acetyl-CoA (leucine and isoleucine) or succinyl-CoA (valine and isoleucine). 

The 2-oxoglutarate produced is recycled for transamination or may enter the TCA cycle. The ammonia liberated by oxidative deamination is used to form glutamine (from glutamate, catalysed by glutamine synthase) prior to export from the muscle cell ... 

---