Lysine inhibition

Reduces accumulation of compoimds such as ammonia, lactate, and other by-products of physical exercise Inhibits platelet aggregation and can also decrease blood pressure Has antioxidant properties Lysine Inhibits herpes virus... 

Dawson Funkhouser, J. Abraham, A. Smith, V.A. Smith W.G. Kinetic and molecular properties of lysine-sensitive aspartokinase. Factors influencing the lysine-mediated association reaction and their relationship to the cooperativity of lysine inhibition. J. Biol. Chem., 249, 5478-5484 (1974)... 

Several plant aspartate kinases are activated by other amino acids such as valine, alanine, and isoleucine (Table HI). Activation does not appear to be a general effect of hydrophobic amino acids, since neither methionine nor leucine influence the activity of the maize enzyme yet, leucine has been reported to activate the enzyme isolated from Sinapsis alba and inhibit the enzyme from Helianthus annus. Interaction of these secondary effectors with the various aspartate kinases has not been fully explored, but several observations suggest a considerable degree of complexity. Alanine partially relieves threonine inhibition of the enzyme isolated from pea seedlings (Aames and Rognes, 1974). Lysine inhibition of maize aspartokinase is diminished in the presence of isoleucine, alanine, or valine (Bryan e/ al., 1970) and threonine, even though it does not inhibit the maize enzyme, counteracts... 

Lysine inhibition of in vivo homocitrate synthesis in PeniciUium chrysogenum. J. Gen. Microbiol, 82, 143-151. 

Poly-L-lysine inhibits the electrode reaction of native horse heart cytochrome c, as shown by dc voltammetry (Figure 3), again analogous to its inhibiting effect on the cytochrome c-oxidase reaction. The effect on the ac cyclic voltammetry peak current, //,(ac), is more marked. The varation with poly-L-lysine concentration is consistent with adsorption of poly-L-lysine onto the electrode surface, decreasing the effective free electrode area. 

The tosyl-phenylalanine moiety mimics a substrate like N-tosyl-phenyl-alanine methyl ester and the chloroketone function (see Section 2.3) acts as an electrophile where the chloride ion is displaced by His-57 at the active site of the enzyme. Similarly, a chloromethylketone analogue of lysine inhibits trypsin. 

SoMERSON, N. L., A. L. Demain, and T. D. Nunheimer Removal of lysine inhibition of penicillin production by a-aminoadipic or adipic acid. Arch. Biochem. Biophys. 93, 238 (1961). 

Sundower Seed. Compared to the FAO/WHO/UNU recommendations for essential amino acids, sunflower proteins are low in lysine, leucine, and threonine for 2 to 5-year-olds but meet all the requirements for adults (see Table 3). There are no principal antinutritional factors known to exist in raw sunflower seed (35). However, moist heat treatment increases the growth rate of rats, thereby suggesting the presence of heat-sensitive material responsible for growth inhibitions in raw meal (72). Oxidation of chlorogenic acid may involve reaction with the S-amino group of lysine, thus further reducing the amount of available lysine. 

Two classes of aldolase enzymes are found in nature. Animal tissues produce a Class I aldolase, characterized by the formation of a covalent Schiff base intermediate between an active-site lysine and the carbonyl group of the substrate. Class I aldolases do not require a divalent metal ion (and thus are not inhibited by EDTA) but are inhibited by sodium borohydride, NaBH4, in the presence of substrate (see A Deeper Look, page 622). Class II aldolases are produced mainly in bacteria and fungi and are not inhibited by borohydride, but do contain an active-site metal (normally zinc, Zn ) and are inhibited by EDTA. Cyanobacteria and some other simple organisms possess both classes of aldolase. 

These observations are explained by the mechanism shown in the figure. NaBH4 inactivates Class I aldolases by transfer of a hydride ion (H ) to the imine carbon atom of the enzyme-substrate adduct. The resulting secondary amine is stable to hydrolysis, and the active-site lysine is thus permanently modified and inactivated. NaBH4 inactivates Class I aldolases in the presence of either dihydroxyacetone-P or fructose-1,6-bisP, but inhibition doesn t occur in the presence of glyceraldehyde-3-P. 

Histone Acetylation. Figure 1 Histone acetylation is a posttranslational modification of lysine residues of histones. This modification is catalyzed by histone actyl transferases (HATs), which transfer an acetyl group (yellow) from acetyl-Coenzyme A onto the E-amino group of the lysine residue. Histone deacetylation is catalyzed by histone deacetylases (HDACs), which hydrolyze the lysine bound acetyl group. HDAC inhibitors like Trichostatin A (TSA) are known to inhibit the deacetylation reaction in vivo and in vitro. 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

Among several thousand species of sea anemones the toxins of only a few dozen have been investigated. Knowledge of the sea anemone peptides permits them to be categorized as (a) sphingomyelin-inhibitable cytolysins, (b) metridiolysin, and (c) Aiptasia lysin. 

Homogenates of MetruUum senile, possibly the world s most common large sea anemone, yield extracts that are powerfully hemolytic for washed mammalian erythrocytes (22). The active substance, metridiolysin, is a protein of molecular weight approximately 80,000. In contrast to the sphingomyelin-inhibitable toxins, metridiolysin is an acidic protein having a pi of about 5. It is thermolabile and is inactivat by proteolytic enzymes. The optimal pH for hemolysis is between 5 and 6, and at pH 8 the lysin is inactive. It can be dissociated into two subunits of unequal size. Besides being cytolytic in vitro, metridiolysin is lethal when injected intravenously into mice. As shown in Table IV erythrocytes from the horse or dog are about a hundred times as sensitive to lysis as those from the mouse, and erythrocytes from other animals tested are intermediate in sensitivity. 

The participation of other lysine residues in ATP hydrolysis is suggested by the inhibition of various partial reactions of Ca transport after modification of -... 

Similarly, the rate of inhibition of phosphoenzyme formation by diethylpyrocarbonate (DEPC) was much slower than the loss of ATPase activity [368], Even when the reaction approached completion with more than 90% inhibition of ATP hydrolysis, about 70% of the Ca -ATPase could still be phosphorylated by ATP (2.3nmoles of E P/mg protein). The remaining 30% of E P formation and the corresponding ATPase activity was not reactivated by hydroxylamine treatment, suggesting some side reaction with other amino acids, presumably lysine. When the reaction of the DEPC-modified ATPase with P-ATP was quenched by histidine buffer (pH 7.8) the P-phosphoenzyme was found to be exceptionally stable under the same conditions where the phosphoenzyme formed by the native ATPase underwent rapid hydrolysis [368]. The nearly normal phosphorylation of the DEPC-trea-ted enzyme by P-ATP implies that the ATP binding site is not affected by the modification, and the inhibition of ATPase activity is due to inhibition of the hydrolysis of the phosphoenzyme intermediate [368]. This is in contrast to an earlier report by Tenu et al. [367], that attributed the inhibition of ATPase activity by... 

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