Essential amino acids acid synthesis

There are two distinct pools of HA in the brain (1) the neuronal pool and (2) the non-neuronal pool, mainly contributed by the mast cells. The turnover of HA in mast cells is slower than in neurons it is believed that the HA contribution from the mast cells is limited and that almost all brain histaminergic actions are the result of HA released by neurons (Haas Panula, 2003). The blood-brain barrier is impermeable to HA. HA in the brain is formed from L-histidine, an essential amino acid. HA synthesis occurs in two steps (1) neuronal uptake of L-histidine by L-amino acid transporters and (2) subsequent decarboxylation of l-histidine by a specific enzyme, L-histidine decarboxylase (E.C. 4.1.1.22). It appears that the availability of L-histidine is the rate-limiting step for the synthesis of HA. The enzyme HDC is selective for L-histidine and its activity displays circadian fluctuations (Orr Quay, 1975). HA synthesis can be reduced by inhibition of the enzyme HDC. a-Fluoromethylhistidine (a-FMH) is an irreversible and a highly selective inhibitor of HDC a single systemic injection of a-FMH (10-50 mg/kg) can produce up to 90% inhibition of HDC activity within 60-120 min (Monti, 1993). Once synthesized, HA is taken up into vesicles by the vesicular monoamine transporter and is stored until released. 

Cysteine is synthesized by two consecutive reactions in which homocysteine combines with serine, forming cystathionine, which, in turn, is hydrolyzed to a-ketobutyrate and cysteine (see Figure 20.8). Homocysteine is derived from methionine as described on p. 262. Because methionine is an essential amino acid, cysteine synthesis can be sustained only if the dietary intake of methionine is adequate. 

A minor pathway of valine catabolism is concerned with its conversion to leucine. Because leucine is an essential amino acid, its synthesis from valine is clearly not sufficiently significant to meet the organism s daily demand for leucine. In this reaction, isobutyryl-CoA (see Figure 20.20) is condensed with a molecule of acetyl-CoA to give /3-ketoisocaproate, which is then transaminated to give (3-leucine. A mutase is then used to convert /3-leucine to leucine. This mutase... 

AA biosynthesis. At an ever deeper level it is possible that high concentrations of the product AA can inhibit expression of the gene for formation of the RNA needed for enzyme synthesis. This form of suppression of gene action over many generations could lead to loss of the gene, causing the AA to become an essential amino acid. 

The other example presented of a non-scrambled distribution of isotopes involves the synthesis of collagen. For a mature animal at steady state, we might expect extensive atomic scrambling in the sense that most of the non-essential amino acid content of this protein (78% of its carbon atoms) can be synthesized from the general pool of glycogenic substrates that arise from metabolism of all sugars and fats, although the pathway from fats is restricted... 

This paper explores how models may be developed to account for the relationship between the stable isotope composition of a body tissue of an organism and its diet. The main approach taken is to express this relationship as an explicit equation, or a DIFF , and then to show how the values of such a DIFF can be evaluated from published experimental data. These values can be expected to have a much wider meaning than a simple encapsulation of a particular experimental design. As a main example, we show how the values may be used to constract a metabolic model in which the synthesis of non-essential amino acid for collagen construction can be treated. A second example is to show how the evaluation, in terms of diet, of the spacing between collagen and carbonate 6 C may be put on a rigorous basis. 

The first step in the synthesis of 5-HT is hydroxylation of the essential amino acid, tryptophan, by the enzyme tryptophan hydroxylase (Fig. 9.4). This enzyme has several features in common with tyrosine hydroxylase, which converts tyrosine to /-DOPA in... 

Figure 9.4 The synthesis and metabolism of 5-HT. The primary substrate for the pathway is the essential amino acid, tryptophan and its hydroxylation to 5-hydrox5dryptophan is the rate-limiting step in the synthesis of 5-HT. The cytoplasmic enzyme, monoamine oxidase (MAOa), is ultimately responsible for the catabolism of 5-HT to 5-hydroxyindoleacetic acid...

Antitumor enzyme, hydrolyzes L-asparagine in bloodstream, depriving tumor cells of the essential amino acid results in inhibition of protein, DNA, and RNA synthesis and cell proliferation derived from Escharichia coli... 

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... 

Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g, L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g, omega-3 fatty acids) can cause a dysregulation of neurottansmitter... 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

The non-essential amino acids are alanine, arginine, aspartate, asparagine, cysteine, glutamate, glutamine, glycine, proline, serine and tyrosine. A summary of the reactions involved in their synthesis is given in Figure 8.3 and full details of these pathways are provided in Appendix 8.2. 

Figure 8.3 A summary of pathways involved in the synthesis of non-essential amino acids. Glutamate is produced from ammonia and oxoglutarate. Glutamate is the source of nitrogen for synthesis of most of the amino acids. Cysteine and tyrosine are different because they require the essential amino acids (methionine and phenylyalanine) for their synthesis. These two amino acids are, therefore, conditionally essential, i.e. when there is not sufficient methionine or phenylyalanine for their synthesis, they are essential (Details are in Appendix 8.2).

Glutamate is required for the synthesis of some non-essential amino acids and key compounds such as glutathione. 

The ratio of essential to non-essential amino acids is high in kwashiorkor but normal in marasmus. The cause of this may be low activities of the enzymes for metabolising the essential amino acids. These are required for any protein synthesis that must take place even in kwashiorkor. 

They are required for the synthesis of conditionally essential amino acids, e.g. arginine, glycine, cysteine and glutamine. 

Free tryptophan is transported into the brain and nerve terminal by an active transport system which it shares with tyrosine and a number of other essential amino acids. On entering the nerve terminal, tryptophan is hydroxylated by tryptophan hydroxylase, which is the rate-limiting step in the synthesis of 5-HT. Tryptophan hydroxylase is not bound in the nerve terminal and optimal activity of the enzyme is only achieved in the presence of molecular oxygen and a pteridine cofactor. Unlike tyrosine hydroxylase, tryptophan hydroxylase is not usually saturated by its substrate. This implies that if the brain concentration rises then the rate of 5-HT synthesis will also increase. Conversely, the rate of 5-HT synthesis will decrease following the administration of experimental drugs such as para-chlorophenylalanine, a synthetic amino acid which irreversibly inhibits the enzyme. Para-chloramphetamine also inhibits the activity of this enzyme, but this experimental drug also increases 5-HT release and delays its reuptake thereby leading to the appearance of the so-called "serotonin syndrome", which in animals is associated with abnormal movements, body posture and temperature. 

In methylcobalamin, X is a methyl group. This compound functions as a coenzyme for several methyltransferases, and among other things is involved in the synthesis of methionine from homocysteine (see p. 418). However, in human metabolism, in which methionine is an essential amino acid, this reaction does not occur. 

L-Lysine is an essential amino acid and is used in veiy large quantities to supplement human foods and animal feeds so as to improve their nutritional quality. Efficient fermentation for its production have been developed in Japan. An alternative production process method involves first the chemical synthesis of DL-df-amino-... 

Homocysteine (Hey) metabolism is closely linked to that of the essential amino acid methionine and thus plays a central role in several vital biological processes. Methionine itself is needed for protein synthesis and donates methyl groups for the synthesis of a broad range of vital methylated compounds. It is also a main source of sulphur and acts as the precursor for several other sulphur-containing amino acids such as cystathionine, cysteine and taurine. In addition, it donates the carbon skeleton for polyamine synthesis [1,2]. Hey is also important in the metabolism of folate and in the breakdown of choline. Hey levels are determined by its synthesis from methionine, which involves several enzymes, its remethylation to methionine and its breakdown by trans-sulphuration. 

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

Humans have no dietary requirement for protein, per se, but, the protein in food does provide essential amino acids (see Figure 20.2, p. 260). Ten of the twenty amino acids needed for the synthesis of body proteins are essential—that is, they cannot be synthesized in humans at an adequate rate. Of these ten, eight are essential at all times, whereas two (arginine and histidine) are required only during periods of rapid tissue growth characteristic of childhood or recovery from illness. 

Proteins from animal sources Proteins from animal sources (meat, poultry, milk, fish) have a high quality because they contain all the essential amino acids in proportions similar to those required for synthesis of human tissue proteins (Figure 27.18). [Note Gelatin prepared from animal collagen is an exception it has a low biologic value as a result of deficiencies in several essential amino acids.]... 

DL-Methionine AMINO ACIDS Synthesis from acrolein and mercaptan First limiting amino acid for soybean... 

L-Aiginine. HC1 102 QUASI ESSENTIAL AMINO ACIDS Synthesis from I-omithine Fermentation (AM) ... 

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