Amino acids endogenous synthesis

Negative Nitrogen Balance if protein intake is insufficient or if the balance of amino acids is incorrect for synthetic needs, endogenous protein is metabolized to liberate free amino acids for synthesis of essential proteins. 

By contrast, the cytoplasmic decarboxylation of dopa to dopamine by the enzyme dopa decarboxylase is about 100 times more rapid (Am 4x 10 " M) than its synthesis and indeed it is difficult to detect endogenous dopa in the CNS. This enzyme, which requires pyridoxal phosphate (vitamin B6) as co-factor, can decarboxylate other amino acids (e.g. tryptophan and tyrosine) and in view of its low substrate specificity is known as a general L-aromatic amino-acid decarboxylase. 

Feedback inhibition of amino acid transporters by amino acids synthesized by the cells might be responsible for the well known fact that blocking protein synthesis by cycloheximide in Saccharomyces cerevisiae inhibits the uptake of most amino acids [56]. Indeed, under these conditions, endogenous amino acids continue to accumulate. This situation, which precludes studying amino acid transport in yeast in the presence of inhibitors of protein synthesis, is very different from that observed in bacteria, where amino acid uptake is commonly measured in the presence of chloramphenicol in order to isolate the uptake process from further metabolism of accumulated substances. In yeast, when nitrogen starvation rather than cycloheximide is used to block protein synthesis, this leads to very high uptake activity. This fact supports the feedback inhibition interpretation of the observed cycloheximide effect. 

Endogenous organic synthesis Urey-Miller experiments as a source of prebiotic molecules via the Strecker synthesis for amino acids, HCN polymerisation for purines and pyrimidines and the formose reaction for sugars... 

Glycine plays an important inhibitory role in the lower brain stem and spinal cord. Little is known about the synthesis of glycine. It activates a Cl- channel, which is antagonized by strychnine. Other endogenous amino acids may activate the glycine channel, such as taurine and j8-alanine. Neuropeptides... 

Figure 8.13 The central role of transdeamination in metabolism of amino adds and further metabolism of the oxoacids in the liver. The box contains the reactions for conversion of the amino acids to their respective oxoacids. Processes are as follows (1) digestion of protein in the intestine and absorption of resultant amino acids, (2) degradation of endogenous protein to amino acids (primarily but not exclusively muscle protein), (3) protein synthesis, (4) conversion of amino acid to other nitrogen-containing compounds (see Table 8.4), (5) oxidation to CO2, (6) conversion to glucose via gluconeogenesis, (7) conversion to fat.

The biosynthetic incorporation of amino acids into proteins makes these metabolites valuable endogenous tracers for the characterization of protein turnover. Of the naturally occurring amino acids, administration of a bolus dose of pH]leucine is widely used as a tracer in kinetic investigations of protein synthesis and secretion. 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

In extreme starvation, both protein and carbohydrate are in short supply. The net effect is that endogenous proteins (from the muscles) are hydrolyzed, releasing amino acids for protein synthesis and for oxidation to yield energy. The 2-oxoacids produced by the aminotransferases either enter gluconeogenesis (Chap. 11) or are metabolized to CO2 and H2O (Chap. 12). Glutamate... 

Subjects who are maintained for prolonged periods by total parenteral nutrition are obviously wholly dependent on what is provided in the nutrient mixture, normally with no contribution from intestinal bacteria. A great deal has been learned from such patients, including the essentiality of the amino acid histidine, and evidence that endogenous synthesis of taurine (Section 14.5.3) and carnitine (Section 14.1.2) may not be adequate to meet requirements without some dietary provision. However, for obvious ethical reasons, such patients have not been subjected to trials of graded intakes of vitamins, but are generally provided with amounts calculated to be adequate and in excess of minimum requirements. 

Creatine is not a dietary essential as shown in Figure 14.5, it is synthesized from the amino acids glycine, arginine, and methionine. However, a single serving of meat will provide about 1 g of preformed creatine, whereas the average daily rate of de novo synthesis is 1 to 2 g, and endogenous synthesis is inhibited by a dietary intake. 

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