Amino acid plasma concentration

In patients with cystinuria, such as Cal Kulis, the inability to normally absorb cystine and basic amino acids from the gut and the increased loss of these amino acids in the urine would be expected to cause a deficiency of these compounds in the blood. However, because three of these amino acids can be synthesized in the body (i.e., they are nonessential amino acids), their concentrations in the plasma remain normal, and clinical manifestations of a deficiency state do not develop. It is not clear why symptoms related to a lysine deficiency have not been observed. 

The inherited enzyme deficiencies listed in Table 11.2 lead to the accumulation of substrates and deficiencies of products. For correct interpretation of laboratory results, one need be aware that substrate accumulation can affect the prior enzyme in the pathway (e.g. increased carbamyl phosphate inhibits CPS). A deficiency of urea cycle intermediates (transport or enzyme products or dietary substances) e.g. arginine or ornithine, is often rate limiting. It can initiate a vicious cycle, which worsens the urea synthetic capacity in the cytosol (e.g. by limiting protein synthesis), or in the mitochondria (deficient stimulation of NAGS and of substrate for OTC). Measured plasma values reflect cytosolic metabolite concentrations, not those of mitochondria. Protein catabolism contributes to the plasma amino acid values. Thus, the interpretation of results for plasma arginine, proline and lysine must be done within the context of the pattern found for all of the amino acids. Urea concentrations depend upon the arginine in the cytosol originating from protein catabolism, urea cycle synthesis, and therapeutic applications. 

Although essential amino acids are requited by both host and tumor, deprivation of select essential amino acids for 2—3 weeks is tolerated by the host yet exerts a pronounced antiproliferative effect on the tumor. Thus, treatment of mice with indole-3-alkane-a-hydroxylase [63363-76-8] from Pseudomonas, which transforms L-tryptophan [73-22-3] to 3-indolylglycaldehyde, lowers the concentration of L-tryptophan in plasma, brain, and lungs, and inhibits the growth of a variety of tumors (32—34). 

Histamine is a critical mediator in anaphylactic reactions. It is a diamine produced by decarboxylation of the amino acid histidine in the Golgi apparatus of mast cells and basophils. Once secreted, it is rapidly metabolized by histamine methyltransferase [2]. Plasma histamine levels are elevated in anaphylaxis, reaching a concentration peak at 5 min and declining to baseline by 30-60 min [3]. Therefore, histamine samples for assessing an anaphylactic reaction should be obtained within 15 min of the onset of the reaction. Urinary metabolites of histamine may be found for up to 24 h. 

Mature human albumin consists of one polypeptide chain of 585 amino acids and contains 17 disulfide bonds. By the use of proteases, albumin can be subdivided into three domains, which have different functions. Albumin has an ellipsoidal shape, which means that it does not increase the viscosity of the plasma as much as an elongated molecule such as fibrinogen does. Because of its relatively low molecular mass (about 69 kDa) and high concentration, albumin is thought to be responsible for 75-80% of the osmotic pressure of human plasma. Electrophoretic smdies have shown that the plasma of certain humans lacks albumin. These subjects are said to exhibit analbuminemia. One cause of this condition is a mutation that affects spUcing. Subjects with analbuminemia show only moderate edema, despite the fact that albumin is the major determinant of plasma osmotic pressure. It is thought that the amounts of the other plasma proteins increase and compensate for the lack of albumin. 

In Saccharomyces cerevisiae, as in most eukaryotic cells, the plasma membrane is not freely permeable to nitrogenous compounds such as amino acids. Therefore, the first step in their utilization is their catalyzed transport across the plasma membrane. Most of the transported amino acids are accumulated inside the yeast cells against a concentration gradient. When amino acids are to be used as a general source of nitrogen, this concentration is crucial because most enzymes which catalyze the first step of catabolic pathways have a low affinity for their substrates. 

The endogenous release of the potent vasoconstrictor neuropeptide Y (NPY) is increased during sepsis and the highest levels are detected in patients with shock (A8). NPY is a 36-amino-acid peptide belonging to the pancreatic polypeptide family of neuroendocrine peptides (T2). It is one of the most abundant peptides present in the brain and is widely expressed by neurons in the central and peripheral nervous systems as well as the adrenal medulla (A3). NPY coexists with norepinephrine in peripheral sympathetic nerves and is released together with norepinephrine (LI9, W14). NPY causes direct vasoconstriction of cerebral, coronary, and mesenteric arteries and also potentiates norepinephrine-induced vasoconstriction in these arterial beds (T8). It appears that vasoconstriction caused by NPY does not counterbalance the vasodilatator effects of substance P in patients with sepsis. The properties of vasodilatation and smooth muscle contraction of substance P are well known (14), but because of the morphological distribution and the neuroendocrine effects a possible stress hormone function for substance P was also advocated (J7). Substance P, which is a potent vasodilatator agent and has an innervation pathway similar to that of NPY, shows a low plasma concentration in septic patients with and without shock (A8). 

ROS can modify amino acid side chains, with histidine, tryptophan, cysteine, proline, arginine, and lysine among those most susceptible to attack (Brown and Kelly 1994). As a result, carbonyl groups are generated, and these carbonyl concentrations can be measured directly in plasma by using atomic absorption spectroscopy, fluorescence spectroscopy, or HPLC following reaction with 2,4-dinitrophenylhydrazine. 

Antithrombin, already mentioned in the context of heparin, is the most abundantly occurring natural inhibitor of coagulation. It is a single-chain 432 amino acid glycoprotein displaying four oligosaccharide side chains and an approximate molecular mass of 58 kDa. It is present in plasma at concentrations of 150 pig ml 1 and is a potent inhibitor of thrombin (factor Ha), as well as of factors IXa and Xa. It inhibits thrombin by binding directly to it in a 1 1 stoichiometric complex. 

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase. Although histamine is present in plasma, it does not penetrate the blood-brain barrier, such that histamine concentrations in the brain must be maintained by synthesis. With a value of 0.1 mmol/1 for L-histidine under physiological conditions, HDC is not saturated by histidine concentrations in the brain, an observation that explains the effectiveness of large systemic doses of this amino acid in raising the concentrations of histamine in the brain. The essential amino acid L-histidine is transported into the brain by a saturable, energy-dependent mechanism [5]. Subcellular fractionation studies show HDC to be localized in cytoplasmic fractions of isolated nerve terminals, i.e. synaptosomes. 

Distortion of the plasma aminogram in individuals with an aminoaciduria also may lead to a relative failure of brain protein synthesis. Thus, in mice with a deficiency of phenylalanine hydroxylase, the blood concentration of phenylalanine is more than 20 times greater than the control value, leading to partial saturation of the transport system and a diminution in the brain level of neutral amino acids other than phenylalanine. Rates of protein synthesis were concomitantly reduced [8]. 

Wagner, M., Coelho, D. M., Barschak, A. G. et al. Reduction of large neutral amino acid concentrations in plasma and CSF of patients with maple syrup urine disease. J. Inker. Metab. Dis. 23 505-512,2000. 

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