Alanine uptake

Sellinger, M., N. Ballatori, and J.L. Boyer. 1991. Mechanism of mercurial inhibition of sodium-coupled alanine uptake in liver plasma membrane vesicles from Raja erinacea. Toxicol. Appl. Pharmacol. 107 369-376. 

Permeability may also be reduced by introducing a freeze-thaw cycle into the reconstitution procedure (Pick, 1981 Anholt et al., 1982) leading to both larger and better sealed vesicles. Finally, Doyle and McGivan (1992) have reported that the incorporation of small quantities (5% mol/mol of phospholipid) of stearylamine into reconstitution procedures decreased cation permeability by increasing vesicle surface charge and improved Na+-coupled alanine uptake by threefold. 

Protein degradation and amino acid metabolism are highly elevated in the diabetic, because the stimulatory effect of insulin on protein synthesis is nonexistent and the relative excess of glucagon and glucocorticoids causes protein breakdown to continue. Indeed, muscle wasting is a cardinal symptom of the untreated diabetic. Insulin also inhibits amino add release into the bloodstream, and this may be a reason a moderate rise in plasma amino add levels is observed in the diabetic. Such increased amino adds are largely of the branched-chain type, and alanine levels are in fact lower than normal. Nevertheless, alanine uptake by the liver is twice that of the normal individual, and it continues to be a major actor in the gluconeogenesis process. 

When alanine is a major end-product of glucose catabolism, substantial amounts of nitrogenous compounds must be available to contribute the amino group. In a number of species alanine formation is accompanied by proteolysis which would release a pool of amino acids from which the nitrogen could be derived. In G. lamblia and Trichomonas vaginalis arginine catabolism is a likely provider of nitrogen for alanine synthesis. The efflux of alanine from G. lamblia is due to an alanine antiport which is also responsible for alanine uptake and acts to maintain a balance between intracellular and extracellular alanine concentrations (36). 

The major site of alanine uptake is the liver, which disposes of the amino nitrogen by incorporating it into urea (see Fig. 42.3). The liver also extracts free amino acids. 

We are led by our results to speculate that if an amino acid residue is present in the peptide as the D-isomer, it may render that peptide unavailable for transport regardless of whether the inverted residue is an alanine, phenylalanine or any other amino acid. And each of the other L-residues in the peptide will he denied entry regardless of their identity or degree of racemiza-tlon. So phenylalanine uptake might he decreased as much as alanine uptake because both of these amino acids finds themselves in D-isomer-containing peptides at about the same frequency. 

In whole cells a considerable Aijj exists in the dark (-40 to -100 mV) but no uptake of alanine takes place. Upon illumination with low light intensities an increase of the Aip is observed but uptake of alanine still does not occur. Alanine uptake is only observed at higher light intensities. The rate of uptake of alanine increases with the light intensity even under conditions that no increase and even a decrease of the Aip is observed. These observations indicate that secondary transport of alanine requires both a proton motive force and electron flow. 

Under conditions of a constant Al the rate of uptake of alanine increases linearly with the light intensity. A threshold light intensity is required before alanine uptake occurs. These results strongly indicate a direct interaction between the alanine carrier and the electron transfer chain. 

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

Hosli E, Hosli L (1980) Cellular localization of the uptake of [3H]taurine and [3H]beta-alanine in cultiu-es of the rat central nervous system. Nemoscience 5(1) 145-152... 

Mutation to leucine in GAT of a highly conserved tryptophan, W681.50, disrupted the release of substrate to the intracellular medium, and the authors inferred from this that TM1 is involved with substrate interactions (58). Mutation to alanine of Pro87i.53 in TM1 or Prol 122.5o in TM2 increased the Km for [3H]dopamine uptake 21-fold and 17-fold, respectively, consistent with either a direct or indirect effect on dopamine binding... 

Finally, loop regions have also been implicated in ligand interactions or their modulation. Chimeras generated between NET and DAT were assayed for ethanol sensitivity and revealed that Glyl302.68 and Ilel373.3i in IL1 are important for ethanol modulation of DAT activity (78). In addition, mutation to alanine of Prol363 30 in IL1, as well as Pro553i2.43 in EL6, decreased the apparent affinity for dopamine uptake (59). 

Teo S, Vore M. 1990. Mirex exposure inhibits the uptake of 17beta-estradiol (beta-D-glucuronide), taurocholate, and L-alanine into isolated rat hepatocytes. Toxicol Appl Pharmacol 104(3) 411- 420. 

Some of the glutamine that is absorbed is metabolised in the enterocytes. It is used, along with glucose, as a fuel to generate ATP (Chapter 8). The ammonia and the alanine that are produced enter the blood for uptake by the liver. 

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

---