Amino acids cerebrospinal fluid

Hyperargininemia. This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase (reaction 5, Figure 29-9), and a urinary amino acid pattern resembling that of lysine-cystinuria. This pattern may reflect competition by arginine with lysine and cystine for reabsorption in the renal tubule. A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria. 

The use of amino acid analysis to characterize protein hydrolyzates is well known, and IEC is an integral part of the commercial amino acid analyzer.61 Determinabon of individual amino acids in physiological fluids such as plasma and cerebrospinal fluid can be important in the etiology of various diseases.62 63 Of particular current interest is the measurement of total... 

Jimenez-Jimenez, F.J., Molina, J.A., Gomez, P., Vargas, C., de Bustos, F., Benito-Leon, J., Tallon-Barranco, A., Orti-Pareja, M., Gasalla, T., and Arenas, J., Neurotransmitter amino acids in the cerebrospinal fluid of patients with Alzhe-imers disease, /. Neural Transm., 105, 269, 1998. 

Preliminary information useful in prodrug design has been obtained with amino acids attached to model aromatic amines. Thus, N-(naphthalen-2-yl) amides of amino acids (6.1, R=side chain of amino acid, R =H) proved to be of interest as test compounds to monitor peptidase activity such as ami-nopeptidase M (membrane alanyl aminopeptidase, microsomal aminopepti-dase, EC 3.4.11.2) [16][17], In the presence of purified rabbit kidney aminopeptidase M or human cerebrospinal fluid (CSF) aminopeptidase activity, the rate of hydrolysis decreased in the order Ala-> Leu->Arg->Glu-2-naphthyl-amide. Ala-2-naphthylamide, in particular, proved to be a good test compound, as its rate of hydrolysis was influenced by experimental conditions (preparation, inhibitors, etc.), as was the hydrolysis of a number of low-molecular-weight opioid peptides and circulating vasoactive peptides. 

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

Determination of amino acids in the analysis of dialyzed rat cerebrospinal fluid Chiral CEC separations of amino acids... 

Mechanism of Action Anantitubercularthat inhibits cell wall synthesis by competing with the amino acid, o-alanine, for incorporation into the bacterial cell wall. Therapeutic Effect Causes disruption of bacf erial cell wall. Bactericidal or bacteriostatic. Pharmacokinetics Readily absorbed from the gastrointestinal (GI) tract. No protein binding. Widely distributed (including cerebrospinal fluid [CSF ). Metabolized in liver. Primarily excreted in urine. Removed by hemodialysis. Half-life 10 hr. 

Ruppel, R.A., Kochanek, P.M., Adelson, P.D., Rose, M.E., Wisniewski, S.R., Bell, M.J., et al. (2001) Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children the role of child abuse. J Pediatr 138 18-25. 

Oxytocin, a nine amino acid peptide, is synthesized primarily in the paraventricular and supraoptic (SON) nuclei of the hypothalamus, from which it is released to the general circulation through the posterior pituitary (Insel et ah, 1997). However, oxytocinergic fibers have also been found to project from the PVN to the limbic system and several autonomic centers in the brain stem. This central OT pool appears to be independent of pituitary OT release cerebrospinal fluid (CSF) and plasma OT responses to numerous stimuli are not correlated (Insel, 1997). Oxytocin and its analog (or partner) peptide vasopressin are found only in mammals. A related peptide, vasotocin, thought to be the evolutionary precedent of these peptides, is found in reptiles and birds. The first known actions of OT were its peripheral effects on the physiology of new mothers. In mammals, OT stimulates milk ejection and uterine contraction, essential aspects of maternal physiology (Insel et ah, 1997). 

Table 2.1.7 Reference values for amino acids in cerebrospinal fluid of subjects of different age groups (pmol/l)...

Cerebrospinal fluid Amino acid 0-1 year 1-18 years >18 years... 

Historically, PA was analyzed with the aid of the amino acid analyzer. The sensitivity of this method is insufficient for reliable determinations in plasma or cerebrospinal fluid (CSF) therefore, more specific and sensitive methods were developed. 

Fig. 6.2.2a-bc High-performance liquid chromatography (HPLC) with electrochemical (EC) detection of neurotransmitter metabolites, a standard mixture b cerebrospinal fluid (CSF) sample - control c CSF sample - aromatic amino acid decarboxylase (AADC) deficiency. Peak identification 1 = 5HIAA (7.7 min), 2 = 3-MD (9.6 min), 3 = HVA (11.7 min)... 

Bito L, Davson H, Levin E, Murray M, Snider N. The concentrations of free amino acids and other electrolytes in cerebrospinal fluid, in vivo dialysate of brain, and blood plasma of the dog. Journal of Neurochemistry 1966, 13, 1057-1067. 

In clinical work many biological fluids have been submitted to paper electrophoretic separation. Serum and urine have been studied extensively and the results were reviewed in Volume I of this series (p. 238). Other fluids include cerebrospinal fluid (B12, B14, E6, K18), pleura] fluid (D4), gastric juice (H6), ascitic fluid (H9), synovial fluid (W3), proteins of the lens (F4, W9, W10), aqueous humor of the eye (W12, W24), edema liquid (W23), and pericardiac effusion (G2). Apart from the general separation of plasma proteins, work has been done on special protein groups, such as lipo- and glycoproteins, muco-proteins, hemoglobins (H19), coagulation factors (05), and on other components, such as amino acids. 

In our studies the ninhydrin-reaction- revealed a number of new fractions, one of which is fluorescent. There are two fractions with a mobility greater than albumin, and two with a mobility lower than y-globulin (Fig. 62b). Some of these are present in many sera, some are rare. They are present in the ultrafiltrate of serum where also a central fraction can be seen, which has the mobility of the y-globulin. They are also present in normal cerebrospinal fluid and were found in hemoglobin preparations. It is not clear if only amino acids are involved, because larger molecules also react with ninhydrin. 

Baker A. J., Moulton R. J., MacMillan V. H., and SheddenP. M. (1993) Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans. J. Neurosurg. 79, 369-372. 

This compound cluster exhibits a two-ring, "open-chained, indolic chemical structure, and in contrast to other psychedelics it is all but inactive when taken orally unless accompanied by certain other compounds. Shortacting tryptamines are closely related to neurotransmitters (such as bufotenine), to MDA (a major botanical source of the snuffs belongs to the nutmeg family), to tryptophan (an essential amino acid produced in human digestion of proteins) and to psilocybin and psilocin (which are tryptamines of longer duration). DMT, the simplest member, occurs normally in the blood, brain and (in higher concentrations) in the cerebrospinal fluid. 

Gu, N. F., Langen, H., He, L., Fountoulakis, M. (2003). Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. Amino Acids 25, 49-57. 

In adcUdon to the biogenic amines, the amino acid neurotransmitters are also implicated in the neurochemistry of major depressive disorder. Neurotransmitter y-aminobutyric acid (GABA) levels are low in brain, cerebrospinal fluid, and blood of padents w ith major depressive disorder (Petty, 1995 Brambilla et al., 2003). 

Blood, urine, cerebrospinal, and other physiological fluids contain a great number of posttranslationally modified amino acids (approximately 170 have been studied to date) and in a wider range of concentrations than protein hydrolysates [6], Additionally, plant sources produce about 500 nonprotein amino acids and, in geological samples, highly unusual amino acids may indicate extraterrestrial origin [7, 8],... 

---