Amino acid, specific uptake rate

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. 

Pool-Loading Experiments and Possibility that Reduction in Incorporation Reduces Influx into Soluble Pool. In order to empirically eliminate the possibility that the observed reduction in uptake of labelled amino acids into the soluble pool was an indirect result of an inhibition of incorporation, it was necessary to experimentally separate the influx and incorporation systems in vivo. The operational compromise required to accomplish this has been given by Sacher (55), and involves in the present case measuring the rates of label incorporation in control and treated tissues which have had their soluble pools fully loaded with unlabelled amino acid. Thus, the label-specific... 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

The specificity of the process so far has been studied most extensively with the glutamate system using the technique of competition. As shown in Table I, a variety of substances diminish the rate of gluta-mate-C14 uptake when presented to the cells simultaneously with this amino acid. Glutamic-C12 acid served as a reference competitive substance. Glutamine is active and at very short incubation periods it sur-... 

Table 7-3 Summary of taxon-specific nitrogen (NO3, NO2, NH +, urea, dissolved free amino acids [DFAA], peptides) uptake rates made in natural systems... 

As a final point, it should be noted that amino acids themselves exhibit some myocardial specificity (71, 72,73) and, thus, the metabolic-ally generated labeled amino acids contribute to total heart uptake and further confuse the issue. One can readily see that this use of N-labeled ammonia as a tracer for myocardial metabolism presents a very complex situation in which determination of even relative metabolic rates is di Scult at best and absolute measurements become virtually impossible. 

The majority of PET studies in oncology have been performed with C-labeled methionine, which is relatively easy to synthesize (41-43). Because of its low uptake in the brain, ["Cjmethionine has been proven to be a sensitive and specific tool for brain tumors, able to differentiate nonneoplastic from malignant lesions (42,44). Methionine uptake reflects the amino acid transport, whereas ["Cjtyrosine has been used to quantify protein synthesis rate in brain tumors (45,46). An I-iodinated tyrosine analog (IMT) also has been proposed to assess tumor cells proliferation by means of SPECT imaging. IMT uptake in glioma cells in vitro (47) and in soft-tissue sarcomas in vivo (48) was shown to be induced by rapid proliferation. 

It is well known that, bacteria, fungi and algae can assimilate and volatilize Se independently of plants and the rates achieved can be considerably higher than in plants. Therefore, the role of the rhizosphere microbes appeared to be somewhat specific for Se04 " and its uptake, by producing heat labile compounds that were proteinaceous in nature possibly the amino acid derivative o-acetylserine and... 

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