Inactivation of metalloenzymes by lysinoalanine, phenylethylaminoalanine, alkali-treated food proteins, and sulfur amino acids.
Synthetic lysinoalanine (LAL) may be a more effective inhibitor of the zinc-containing enzyme carboxypeptidase A than is ethylenediamine tetraacetic acid (EDTA). The enzyme is also inactivated by alkali-treated, lysinoalanine-containing food proteins such as casein, high-lysine corn protein, lactalbumin, soy protein isolate, and wheat gluten, and by alkali-treated zein, which contains no lysinoalanine. Zinc sulfate regenerates only part of the enzymatic activity after exposure to the treated proteins. The extent of inhibition increases with protein concentration and time of treatment. Any inhibition due to phytate is distinct from that due to the treatment. Phenylethylaminoalanine (PEAA), derived from biogenic phenylethylamine, inhibited enzymatic activity of the metalloenzyme carboxypeptidase A (CPA). The inhibition was maximal at pH 7.0 in the pH range 7 to 8.5. The extent of inhibition increased with time of treatment and PEAA concentration. N-acetyl-PEAA did not inhibit the enzyme, suggesting that the free alpha-NH2 group is required for inhibition. PEAA, LAL, sodium phytate, and cysteine also inactivated the copper enzyme, polyphenol, oxidase (tyrosinase) which plays a major role in enzymatic (oxidative) browning of foods. Analogous comparative studies with LAL, EDTA, and sodium phytate suggest that the potency of PEAA as an inhibitor of CPA is similar to that of sodium phytate, and that of the four compounds tested, PEAA is least effective against tyrosinase. Related studies of the iron and copper containing enzyme cytochrome C oxidase showed that EDTA was not inhibitory, PEAA was slightly inhibitory, and LAL and sodium phytate were stronger inhibitors. Mechanistic explanations are offered to account for some of these observations. The possible relevance of these findings to in vivo protein digestion, enzymatic (oxidative) browning of foods, and the mechanism of the lysinoalanine effect on kidney cells are also discussed.
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D004156:Catechol Oxidase / Q000037:antagonists & inhibitors*; D003545:Cysteine / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives*; D008241:Lysinoalanine / Q000494:pharmacology*; D008667:Metalloproteins / Q000037:antagonists & inhibitors*; D010627:Phenethylamines / Q000494:pharmacology*; D011485:Protein Binding; D011492:Protein Hydrolysates / Q000494:pharmacology*
D004044:Dietary Proteins; D008667:Metalloproteins; D010627:Phenethylamines; D011492:Protein Hydrolysates; D008241:Lysinoalanine; C050457:3-((2-phenylethyl)amino)alanine; D004156:Catechol Oxidase; D003576:Electron Transport Complex IV; D000469:Alkaline Phosphatase; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D008239:Lysine; D003545:Cysteine