Nonessential Amino Acid Synthesis

Nonessential Amino Acid Synthesis Essential Amino Acids Amino Acid Degradation Generalities of Amino Acid Catabolism Products of Amino Acid Degradation 

Phe Tyr (phenylalanine hydroxylase, biopterin cofactor) Met homoCys + Ser cystathionine Cys 

The other nine amino acids are essential and must be taken from the diet. Notice that some of the amino acids require other amino acids for their synthesis. Exam questions usually center on whether or not an amino acid is essential and the metabolites that serve as precursors for specific amino acids. 

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The removal of the a-amino group from amino acids involves two types of biochemical reactions transamination and oxidative deamination. Both reactions have been described (Section 14.2). (Recall that transamination reactions occupy important positions in nonessential amino acid synthesis.) Because these reactions are reversible, amino groups are easily shifted from abundant amino acids and used to synthesize those that are scarce. Amino groups become available for urea synthesis when amino acids are in excess. Urea is synthesized in especially large amounts when the diet is high in protein or when there is massive breakdown of protein, for example, during starvation. 

Therapy with L-asparaginase is most successful against tumors exhibiting a deficiency in the synthesis of L-asparagine. Most normal cells exhibit a healthy capacity to synthesize this nonessential amino acid and are not damaged by exposure to L-asparaginase (23). This finding demonstrates that biochemical differences between normal and cancer cells can be exploited for successful cancer chemotherapy. 

A substrate is a substance that is the basic component of an organism. Protein substrates are amino acids, which are essential to life Protein substrates are amino acid preparations that act to promote the production of proteins (anabolism). Amino acids are necessary to promote synthesis of structural components, reduce the rate of protein breakdown (catabolism), promote wound healing, and act as buffers in the extracellular and intracellular fluids. Crystalline amino acid preparations are hypertonic solutions of balanced essential and nonessential amino acid concentrations that provide substrates for protein synthesis or act to conserve existing body protein. 

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. 

Historically, elemental formulas designed for renal failure were enriched with essential amino acids (EAAs) and contained lesser amounts of nonessential amino acids (NEAAs) than standard formulas. Theoretically, EAAs could combine with urea nitrogen in the synthesis of NEAAs, thus leading to a decrease in blood urea nitrogen (BUN). The only situation in which such formulas may be appropriate is in patients with... 

Anabolism encompasses the synthesis of complex macromolecules and structures from building blocks derived from nutrients as well as synthesis of the building blocks themselves, such as nonessential amino acids. 

Equation for the Synthesis of Aspartate from Glucose Write the net equation for the synthesis of aspartate (a nonessential amino acid) from glucose, carbon dioxide, and ammonia. 

These free amino acids are obtained from the degradation of dietary protein, the constant turnover of body protein, and the synthesis of nonessential amino acids. Free amino acids are consumed by synthesis of body protein and metabolism of their carbon skeletons. 

L-Glutamic acid 105 NONESSENTIAL AMINO ACIDS Fermentation (WS) Synthesis from acrylonitrile and resolution MSG. taste enhancer... 

RNA base triplets (codons) exist for the 20 amino acids used in protein synthesis (Chap. 17). The ability of an organism to live and grow is dependent on protein synthesis and hence on a supply of all 20 amino acids. Higher plants are able to synthesize all 20, but many microorganisms and higher animals make considerably fewer. Humans make 10 of the 20 amino acids the remainder must be supplied in the diet, usually in the form of plant or animal protein. The amino acids that humans cannot synthesize de novo but are essential for life are termed the essential amino acids. Those that we can synthesize are called the nonessential amino acids. The essential and nonessential amino acids are listed in Table 15.1. 

Certain 2-oxoacids are necessary for the synthesis of the nonessential amino acids they are listed in Table 15.2. 

Four of the amino acids, alanine, aspartate, glutamate, and serine, are formed by the transamination of their corresponding oxoacids. The other nonessential amino acids are then derived from these four amino acids. The syntheses of serine and tyrosine are described below because of either their importance in aspects of metabolism or their clinical significance the synthesis of serine is essential for folic acid metabolism, while deficiencies in the enzymes synthesizing tyrosine can lead to phenylketonuria. 

Table 15.2. 2-Oxoacids Required for Synthesis of the Nonessential Amino Acids...

Two of the nonessential amino acids, tyrosine and cysteine, are derived from essential amino acids and may be considered to be breakdown products, as they are intermediates in the normal degradation of these amino acids. Provided sufficient of the two essential amino acids phenylalanine and methionine are available through the diet, net synthesis of tyrosine and cysteine can occur. 

Vitamin Be has a central role in the metabolism of amino acids in transaminase reactions (and hence the interconversion and catabolism of amino acids and the synthesis of nonessential amino acids), in decarboxylation to yield biologically active amines, and in a variety of elimination and replacement reactions. It is also the cofactor for glycogen phosphorylase and a variety of other enzymes. In addition, pyridoxal phosphate, the metabolically active vitamer, has a role in the modulation of steroid hormone action and the regulation of gene expression. 

Transamination is of central importance in amino acid metabolism, provid-ingpathwaysforthe catabolism of aU amino acids other than lysine (which does not undergo transamination), although pathways other than transamination may be more important for the catabolism of some amino acids. It also provides a pathway for the synthesis of those amino acids for which there is an alternative source of the oxo-acid (the nonessential amino acids). As can be seen from Table 9.3, many of the oxo-acids are common metabolic intermediates. 

The nonessential amino acids are synthesized by quite simple reactions, whereas the pathways for the formation of the essential amino acids are quite complex. For example, the nonessential amino acids alanine and aspartate are synthesized in a single step from pyruvate and oxaloacetate, respectively. In contrast, the pathways for the essential amino acids require from 5 to 16 steps (Figure 24.8). The sole exception to this pattern is arginine, inasmuch as the synthesis of this nonessential amino acid de novo requires 10 steps. Typically, though, it is made in only 3 steps from ornithine as part of the urea cycle. Tyrosine, classified as a nonessential amino acid because it can be synthesized in 1 step from phenylalanine, requires 10 steps to be synthesized from scratch and is essential if phenylalanine is not abundant. We begin with the biosynthesis of nonessential amino acids. 

We turn now to the biosynthesis of essential amino acids. These amino acids are synthesized hy plants and microorganisms, and those in the human diet are ultimately derived primarily from plants. The essential amino acids are formed by much more complex routes than are the nonessential amino acids. The pathways for the synthesis of aromatic amino acids in bacteria have been selected for discussion here because they are well understood and exemplify recurring mechanistic motifs. 

Figure 24.8. Essential and Nonessential Amino Acids. Some amino acids are nonessential to human beings because they can be biosynthesized in a small number of steps. Those amino acids requiring a large number of steps for their synthesis are essential in the diet because some of the enzymes for these steps have been lost in the course of evolution.

Human beings can synthesize 11 of the basic set of 20 amino acids. These amino acids are called nonessential, in contrast with the essential amino acids, which must be supplied in the diet. The pathways for the synthesis of nonessential amino acids are quite simple. Glutamate dehydrogenase catalyzes the reductive amination of a-... 

Serine, glycine, and cysteine are dispensable (or nonessential) amino acids because they can be biosynthesized from precursors that are readily available in the body Serine can be made from or converted back to glucose, and also is used in the synthesis of cysteine. The pathways for these conversions are detailed in Chapter 8. 

Protein is an essential nutrient for human growth, development, and homeostasis. The nutritive value of dietary proteins depends on its amino acid composition and digestibility. Dietary proteins supply essential amino acids, which are not synthesized in the body. Nonessential amino acids can be synthesized from appropriate precursor substances (Chapter 17). In human adults, essential amino acids are valine, leucine, isoleucine, lysine, methionine, phenylalanine, tryptophan, and threonine. Histidine (and possibly arginine) appears to also be required for support of normal growth in children. In the absence from the diet of an essential amino acid, cellular protein synthesis does not occur. The diet must contain these amino acids in the proper proportions. Thus, quality and quantity of dietary protein consumption and adequate intake of energy (carbohydrates and lipids) are essential. Protein constitutes about 10-15% of the average total energy intake. 

Maintenance of amino acid balance. Metabolic pathways for the degradation of most amino acids and for the synthesis of nonessential amino acids involve some steps of the gluconeogenic pathway. Imbalances of most amino acids, whether due to diet or to an altered metabolic state, are usually corrected in the liver by degradation of the excess amino acids or by synthesis of the deficient amino acids through gluconeogenic intermediates. 

Plants and some bacteria synthesize all 20 amino acids (see also Chapter 2). Humans (and other animals) can synthesize about half of them (the nonessential amino acids) but require the other half to be supplied by the diet (the essential amino acids). Diet must also provide a digestible source of nitrogen for synthesis of the nonessential amino acids. The eight essential amino acids are isoleucine, leucine lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In infants, histidine (and possibly arginine) is required for optimal development and growth and is thus essential. In adults, histidine is nonessential, except in uremia. Under certain conditions. 

Some general reactions that involve degradation or interconversion of amino acids provide for the synthesis of nonessential amino acids from a-keto acid precursors derived from carbohydrate intermediates. 

This is the pathway for synthesis of arginine, a nonessential amino acid however, in the event of physiological deficiency, as in premature infants, or a defect in any of... 

Of the 20 amino acids in proteins, the body can readily synthesize eight if an appropriate nitrogen source is available. Two others can be synthesized from other amino acids of the diet tyrosine from phenylalanine and cysteine from methionine. The rest must be provided in the diet (Chapter 17), since the body can synthesize none or an insufficient amount. The dietary requirement depends on several factors. Beside essential amino acids, the diet should provide the nitrogen required for synthesis of the nonessential amino acids. 

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