Amino acid fates

The synthesis of virtually all proteins in a cell begins on ribosomes in the cytosol (except a few mitochondrial, and in the case of plants, a few chloroplast proteins that are synthesized on ribosomes inside these organelles). The fate of a protein molecule depends on its amino acid sequence, which can contain sorting signals that direct it to its corresponding organelle. Whereas proteins of mitochondria, peroxisomes, chloroplasts and of the interior of the nucleus are delivered directly from the cytosol, all other organelles receive their set of proteins indirectly via the ER. These proteins enter the so-called secretory pathway (Fig. 1). 

Figure 15-5. Transport and fate of major carbohydrate and amino acid substrates and metabolites. Note that there is little free glucose in muscle, since it is rapidly phosphorylated upon entry.

Section III deals with the amino acids and their many fates and also describes certain key features of protein catabolism. 

The application of substrates isotopically labeled in specific positions makes it possible to follow the fate of individual atoms during the microbial degradation of xenobiotics. Under optimal conditions, both the kinetics of the degradation, and the formation of metabolites may be followed— ideally when samples of the labeled metabolites are available. Many of the classical studies on the microbial metabolism of carbohydrates, carboxylic acids, and amino acids used radioactive... 

The interaction of platinum(II) complexes with various amino acids and simple peptides is relevant to understanding the biological fate of platinum anticancer agents such as mplatin, and this area has been reviewed extensively.258-261... 

The major metabolic fate of amino acids is conversion into organic acids absent an enzyme to oxidize an organic acid, an organic aciduria results 668... 

The major metabolic fate of amino acids is conversion into organic acids absent an enzyme to oxidize an organic acid, an organic aciduria results. Three features characterize the metabolism of essentially all amino acids (1) incorporation into protein (2) conversion into messenger compounds such as hormones and neurotransmitters ... 

Aspartame, N-a-L-aspartyl-L-phenylalanine methyl ester, trade names NutraSweet , and Aspartil , is a dipeptide derivative. Like dipeptides aspartame is metabolised into the constituents, i.e. amino acids and methanol. Therefore studies into the metabolic behaviour and the fate of metabolites were carried out. Levels of blood aspartate and glutamate were measured after intake of high aspartame doses. Changes were transient and allegations of influences of high aspartame levels on brain function could never be verified. 

Some experiments had already indicated the fate of the C skeletons of the amino acids. Kossel (1898) was the first to suggest protein could be catabolized to glucose. This was proved by Stiles and Lusk... 

Proapototic signals direct these proteins to mitochondria where they compete with antiapoptotic members of the Bcl-2 family to regulate the cytochrome c release and to determine the fate of the cell life or death (Cosulich et al., 1999). Unlike proapoptotic proteins, the antiapoptotic Bcl-2 proteins reside in the outer mitochondrial membrane, anchored by a hydrophobic stretch of amino acids located at the COOH-termini,... 

Oxoacids derived from amino acids After a meal containing protein, the amino acids that are absorbed into the blood are largely metabolised in the liver (>70%) and muscle. Most of these are converted to oxoacids which have two main fates ... 

There are three major fates of amino acids ... 

It is the rates of these various processes that control the magnitude and direction of flux through the transdeamination system and the eventual fate of the amino acids in various conditions. These are discussed for several conditions the normal fed state starvation trauma, surgery and cancer. 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

Figure 8.24 Some fates of glutamine that is released by muscle. Glutamine is released from the store of glutamine in the muscle but, for immune system and bone marrow, it may also be provided from adipocytes (Chapter 17). It is assumed that glutamine is present as a free amino acid in muscle and that there is a specific transport protein in the plasma membrane that can be regulated.

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.

Macromolecules as drug carriers may be divided into degradable and nondegradable types based on their fate within the organism. Biodegradable polymeric drug carriers are traditionally derived from natural products polysaccharides, poly(amino acids) in the hope that the body s natural catabolic mechanisms will act to break down the macromolecular structure into small,... 

An alternative fate for the GSH conjugate is transportation via the blood to the kidney, filtration out of the blood and in the brush border of the tubular cells glutamyltransferase, and cleavage of the conjugate by a dipeptidase to yield the cysteine conjugate. The cysteine conjugate is then taken up by the amino acid transporter system into the proximal tubular cell where toxicity occurs. The result of this is then basically the same as the other scenario. 

The oxidation of pyruvate is an important catabolic process, but pyruvate has anabolic fates as well. It can, for example, provide the carbon skeleton for the synthesis of the amino acid alanine. We return to these anabolic reactions of pyruvate in later chapters. 

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. 

The interconnected cycles have been called the "Krebs bicycle." The pathways linking the citric acid and urea cycles are called the aspartate-argininosuccinate shunt these effectively link the fates of the amino groups and the carbon skeletons of amino acids. The interconnections are even more elaborate than the arrows suggest. For... 

A discussion of the various fates of amino acids in plants. 

Phosphoribosyl pyrophosphate (PRPP) is important in both, and in these pathways the structure of ribose is retained in the product nucleotide, in contrast to its fate in the tryptophan and histidine biosynthetic pathways discussed earlier. An amino acid is an important precursor in each type of pathway glycine for purines and aspartate for pyrimidines. Glutamine again is the most important source of amino groups—in five different steps in the de novo pathways. Aspartate is also used as the source of an amino group in the purine pathways, in two steps. 

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