Alanine inhibition

A biochemical evalution of human alkaline phosphatase is postponed until the above considerations have been presented. In our view, the most reasonable analytical approach is based on the measurement of L-phenyl-alanine-sensitive and -insensitive moieties along with their respective heat stabilities. To this may be added information gathered from starch-gel electrophoresis with native and heated serum and from the presence of L-phenylalanine-sensitive bands on the gels following electrophoresis. Experiments of a different type can be included, in which the serum is incubated with neuraminidase and susceptibility of the glycoprotein is established following electrophoresis. Finally, the data on L-phenyl-alanine inhibition of heat-sensitive and -insensitive moieties appear to make sense, if the population of normal subjects is divided into one with the slow-moving intestinal band and one without it. It is from this consideration and other indirect and direct inferences that the intestine is... 

In aerobic animals, the K , for PEP is well below the concentration of this substrate in the cell so that enzyme function is never substrate-limited. Alanine is a very poor inhibitor of the aerobic enzyme form and at physiological levels of alanine there would be very little effect of this inhibitor on the aerobic enzyme. A complete reversal occurs in the anoxic situation, however. In vivo levels of PEP drop and the for PEP rises so that substrate concentration in vivo is now 17-fold lower than the value. This situation greatly reduces enzyme activity in vivo (Figure 1). In addition, alanine inhibition of the anoxic PK form is so strong that enzyme activity is virtually undetectable at physiological alanine levels. 

The nonessential amino acid, L-alanine, has been reported to compete with tryptophan binding to hepatic nuclei in vitro.174485 However, L-alanine is not capable of stimulating hepatic protein synthesis as does L-tryptophan.185 Yet, L-alanine in competing with L-tryptophan for nuclear receptor binding is able to diminish or negate L-tryptophan s ability to stimulate hepatic protein synthesis.185 Similarly, DL- 3(l-naphthyl)alanine is capable of acting like L-alanine.173 Also, L-alanine inhibited elevations of other rapidly induced metabolic reactions, such as nuclear RNA efflux and nuclear poly(A)polymerase activity, which occurred due to L-tryptophan alone. These two stimulatory... 

M.L. Paddock, P.H. McPherson, G. Feher, and M.Y. Okamura, Pathway of proton transfer in bacterial reaction centers replacement of serine-L223 by alanine inhibits electron and proton transfers associated with reduction of quinone to dihy-droquinone, Proc. Natl. Acad. Sci. USA 87 6803 (1990). 

Alanine, ( )- -(2-amino-1,3-selenazol-4-yl)-synthesis, 6, 343 Alanine, phenyl-p-hydroxylation, 7, 565 Alanine, selenienyl-synthesis, 4, 964 Alanine, y3-2-selenienyl-applications, 4, 970 Alanine, y3-3-selenienyl-applications, 4, 970 Alanine, y3-2-thienyl-biological activity, 4, 911 Alanine, -3-thienyl-biological activity, 4, 912 L-Alanine, y-L-glutamyl-y3-pyrazolyl-occurrence, 5, 303 L-Alanine, -pyrazolyl-occurrence, 5, 303 Alanine raeemase inhibition, 1, 266 Albendazole... 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

Nishimura and coworkers57-59 studied the y-radiolysis of aqueous solutions of sulfoxide amino acids. Sulfoxide amino acids are the precursors of the flavors of onions (S-propyl-L-cysteine sulfoxide, S-methyl-L-cysteine sulfoxide and S-(l-propenyl)-L-cysteine sulfoxide) and garlic (S-allyl-L-cysteine sulfoxide). In studies on sprout inhibition of onion by /-irradiation it was found that the characteristic flavor of onions became milder. In the y-radiolysis of an aqueous solution of S-propyl-L-cysteine sulfoxide (PCSO)57,58 they identified as the main products alanine, cysteic acid, dipropyl disulfide and dipropyl sulfide. In the radiolysis of S-allyl-L-cysteine sulfoxide (ACSO) they found that the main products are S-allyl-L-cysteine, cysteic acid, cystine, allyl alcohol, propyl allyl sulfide and diallyl sulfide. The mechanisms of formation of the products were partly elucidated by the study of the radiolysis in the presence of N20 and Br- as eaq - and OH radicals scavengers, respectively. 

Neutrophils represent an ideal system for studying osmotic effects on exocytosis. Stimulation of cytochalasin-B-treated neutrophils with the chemotactic peptide Jlf-formylmethionyl-leucyl-phenyl-alanine (FMLP) results in a rapid compound exocytosis up to 80% of lysosomal enzymes are released within 30 s (9-14). Secretion appears to be triggered by a rise in the level of cytosolic free calcium (15-18) promoted in part by entry of extracellular calcium through receptor-gated channels and in part by release of calcium that is sequestered or bound at some intracellular site (19-21). In this presentation, we augment our previously published data (22,23), which demonstrates that lysosomal enzyme release from neutrophils is inhibited under hyperosmotic conditions and that the rise in cytosolic calcium preceding secretion is inhibited as well. 

Fig. 3.15 Model for allosteric inhibition of a protein-DNA complex by a polyamide-inter-calator conjugate. (Top) The GCN4 homodimer (yellow) is displaced by the intercalating moiety (green) of the polyamide conjugate. Blue and red spheres represent pyrrole and imidazole amino acids, respectively. The blue diamond represents / -alanine. (Bottom, left) Hydrogen-bonding model of an eight-ring hairpin polyamide-intercalator conjugate...

Fig. 8.1 Biosynthesis of peptidoglycan. The large circles represent A -acetylglucosamine orN-acetylmuramic acid to the latter is linked initially a pentapeptide chain comprising L-alanine, D-glutamic acid and meso-diaminopiraelic acid (small circles) terminating in two D-alanine residues (small, darker circles). The lipid molecule is undecaprenyl phosphate. In the initial (cytoplasm) stage where inhibition by the antibiotic D-cycloserine is shown, two molecules of Dalanine (small circles) are converted by an isomerase to the D-forms (small, darker circles), alter which a ligase joins the two D-alanines together to produce a D-alanyl-D-alanine dipeptide.

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

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