Amino acids transport

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Some Mammalian Amino Acid Transport Systems ... 

Increased protein synthesis Increased amino acid uptake/increased translation of mRNA Akt-mediated stimulation of system A amino acid transporter and stimulation of mRNA-translation through activation of p70S6kinase and elongation initiation factor 4 (elF4). Possible involvement of atypical PKCs... 

Kanai Y, Hediger MA (2004) The glutamate/neutral amino acid transporter family SLC1 molecular, physiological and pharmacological aspects. Pfliigers Arch 447 469-479... 

Orexin neurons, likely to be glutamatergic themselves, express the excitatory amino acid transporter EAAT3, vesicular glutamate transporters VGLUT1 and VGLUT2, secretogranin II, ionotropic (NMDAR,... 

Vesicular GABA transporter vesicular inhibitory amino acid transporte. 

Transport systems can be described in a functional sense according to the number of molecules moved and the direction of movement (Figure 41-10) or according to whether movement is toward or away from equilibrium. A uniport system moves one type of molecule bidirectionally. In cotransport systems, the transfer of one solute depends upon the stoichiometric simultaneous or sequential transfer of another solute. A symport moves these solutes in the same direction. Examples are the proton-sugar transporter in bacteria and the Na+ -sugar transporters (for glucose and certain other sugars) and Na -amino acid transporters in mammalian cells. Antiport systems move two molecules in opposite directions (eg, Na in and Ca out). 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

Palacin, M, Estevez, R, Bertran, J and Zorzano, A (1998) Molecular biology of mammalian plasma membrane amino acid transporters. Physiol. Rev. 78 969-1054. 

From a genetical point of view, Saccharomyces cerevisiae is an ideal organism which may be considered the Escherichia coli of eukaryotic cells [4,5]. This is true in particular for the study of metabolic regulation and for that of membrane transport [6]. Finally, the astonishing resemblance between many yeast proteins and certain mammalian-cell proteins has seriously broadened the scope of interest. Although a few reports have appeared on amino acid transport in some other yeasts, most investigations in this field have used strains of Saccharomyces cerevisiae. 

In this chapter, we shall focus on the molecular aspects of amino acid transport and its regulation in Saccharomyces cerevisiae. Kinetic, biochemical and genetic aspects of the amino acid transport systems of eukaryotic microorganisms have been reviewed earlier [7,8]. 

General characteristics of amino acid transporters in Saccharomyces cerevisiae... 

Furthermore, the multiplicity and diversity of amino acid transporters allow yeast to accumulate amino acids for both biosynthesis and catabolism under a... 

A large number of amino acid transporters have been detected by isolating mutations which selectively inactivate one permease without altering enzyme activities involving the corresponding amino acid. Competitive inhibition, kinetics and regulatory behaviour have also been used as criteria to distinguish one transport system from another (see section 4.2). 

Despite the limited information available, rather clear predictions can be made about the probable structure, location, and energy coupling of the amino acid transporters of Saccharomyces cerevisiae, by comparing them with better known systems in both prokaryotes and eukaryotes. 

A family of amino acid transporters with amino acid sequence homologies... 

The proline transport protein prnB of Aspergillus nidulans [47] is very similar to the above-mentioned family of Saccharomyces cerevisiae amino acid transporters (about 42% identity with the PUT4 gene product and 30% identity with the CANl and the HIP I gene products). So is the AroP general aromatic amino acid transporter protein of Escherichia coli K-12, which has about 30% identity with the HIPI gene product [48]. Both hydrophilic ends are very different from one transporter to another (see Fig. 2). 

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. 

To study the specific regulation of the synthesis of NCR-sensitive amino acid transporters, Saccharomyces cerevisiae cells are grown with proline or urea as the sole source of nitrogen, i.e., in the absence of NCR (see section 6.3). 

Substantial progress can be expected in the near future concerning the structure of amino acid transporters, their functional dissection, and their evolutionary filiation. 

The regulation of NCR-sensitive amino acid transporters in Saccharomyces cerevisiae has many points in common with that of catabolic enzymes. Amino acid permeases, as well as some other transporters of nitrogenous nutrients, are integrated into the regulatory circuits, both general and specific, which control catabolic processes. 

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