Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catechol analogs inhibit the formation of hydroxylysine-derived intermolecular collagen cross links in tissue cultures of chick embryo calvaria. Formation of intermolecular collagen cross links was measured following incorporation of [14C]lysine, reduction with sodium borohydride, and elution from an ion exchange column with a pyridine-formate gradient. Cultures grown in the presence of 10(-3) M catechol, 10(-3) M dopamine, 10(-3) M L-dopa, or 10(-3) M D,L-serine-(2,3,4-trihydroxybenzyl)-hydrazide demonstrated between 43 and 84% inhibition of hydroxylysine formation. Collagen biosynthesis was not diminished in these cultures as compared to controls without additions or with beta-aminopropionitrile when measured by collagenase digestion. The formation of hydroxylysine-derived intermolecular cross links was inhibited 34 to 93% for 5,5'-dihydroxylysinonorleucine and 7 to 71% for 5-hydroxylysinonorleucine. The catechol analogs also inhibit the activity of lysyl hydroxylase as measured by specific tritium release as triated water from an L-[4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Since catechol analogs inhibit the formation of hydroxylysine in a cell-free assay, these compounds must pass into the cells of calvaria in this culture system to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross links of the newly synthesized collagen.
J Invest Dermatol 1977 Mar
PMID:In vitro inhibition of collagen cross links by catechol analogs. 1 15

The possible presence of epsilon-(gamma-glutamyl) lysine covalent bonds in human epidermal proteins prompted a study of transamidase activity in human hair-free epidermis. Callus contains an enzyme which catalyzes the incorporation of radioactive putrescine into alpha-casein. The enzyme is active without prior treatment with exogenous proteolytic enzymes. The putrescine incorporation is calcium dependent and inhibited by iodoacetamide. The enzyme was partially purified (50-fold over starting material), and has an apparent molecular weight between 50,000 daltons and 55,000 daltons by agarose 0.5m gel filtration. The apparent molecular weight is unaltered by chromatography in the presence of 11 mMCaCl2, a condition known to dissociate plasma transglutaminase (Factor XIII) into its ultimate subunits. The enzyme is active over a wide pH range up to pH 10.4 The Km for putrescine varies by 1-fold over the pH range 6.0 to 10.2, although enzyme activity increases at least 20-fold over the same pH range. The human epidermal transamidase is similar to the guinea-pig hair follicle transglutaminase and cow snout transamidase in its ability to cross-link fibrin.
J Invest Dermatol 1975 May
PMID:Human epidermal transamidase. 23 63

Enzymes known as transglutaminases mediate cross-linking of polypeptide chains by epsilon-(gamma-glutamyl) lysine bonds. Such bonds stabilize structural proteins of many tissues; transglutaminases specific for these tissues have been identified. A calcium- and sulfhydryl-dependent transglutaminase with a molecular weight of 55,000 has been purified from bovine snout epidermis and used to elicit a specific antiserum to the enzyme. Sites of epidermal transglutaminase activity have been localized in the cytoplasm of upper malpighian and granular cells by two complementary methods. When thin-tissue sections were incubated with a fluorescent lysine analog(dansyl cadaverine) and calcium, tissue acceptor sites became fluorescent. Localization was confirmed by fluorescein-conjugated antibody labeling of the enzyme in situ. These observations indicate that epidermal transglutaminase cross-links epidermal proteins during the final stages of keratinization.
J Invest Dermatol 1975 Jul
PMID:Keratin cross-linking and epidermal transglutaminase. A review with observations on the histochemical and immunochemical localization of the enzyme. 23 69

A method is presented for the separation of epidermal strata by the successive elimination of either the basal or basal and spinous cells with 0.24 M NH4Cl at pH 9.5. Histologic evidence suggests that the residual epidermal strata obtained after incubation of the skin with NH4Cl are reproducible; hence, this technique circumvents loss of granular layer histidine-rich protein inherent with trypsin separation and provides an effective procedure for biochemical analysis of arginine-rich and lysine-rich proteins in the various differentiating epidermal cells.
J Invest Dermatol 1977 Feb
PMID:Separation of epidermal layers of the newborn rat. 31 73

A kinin-forming-enzyme in human skin extract was further purified by successive column chromatography on DEAE-cellulose, Hydroxylapatite-cellulose and Sepharose-4B. By these procedures, 2.7 mg of purified enzyme was obtained from 10 gm of original skin. The purified material was homogeneous as ascertained by cellulose acetate membrane electrophoresis, sodium dodecyl sulfate polyacrylamide gel disc electrophoresis and ultracentrifugation. It had an S20,w value of 4.3 and an apparent molecular weight of 104,000 as measured by gel filtration on Sephadex G-200. The purified enzyme was comparatively heat-stable, but was unstable below pH values of 5 and above pH 9. It possessed arginine or lysine esterolytic activity, but not tyrosine or tryptophane esterolytic activity and denatured proteolytic activity. This enzyme was not affected by metal ion, cystein, glutathion or rho-chloromercuribenzoate, but was strongly inhibited by alpha-N-rho-tosyl-L-lysine chloromethyl ketone or soybean-trypsin inhibitor. It was also inhibited by alpha 1-antitrypsin, but not by alpha 2-macroglobulin. This enzyme was confirmed to be immunologically distinct from human plasma, urinary or pancreas kallikrein.
J Invest Dermatol 1979 Oct
PMID:Kinin-forming enzyme in human skin: the purification and characterization of a kinin-forming enzyme. 47 33

With the aid of ion exchange column chromatography we determined quantitatively the free amino acids in eccrine, thermal sweat. Sweat was collected (a) from the face of 27 healthy men and 26 healthy women (b) from the face, chest, armpits, shoulders, back, upper part of the abdomen, hypogastrium, forearms and thighs of the same individual and (c) from the face of the same individual at different times. Sweat was deproteinised by adding an equal volume of 5% sulphosalicylic acid. 1. The results showed not only a constant, qualitative amino acid pattern in sweat, but also a relative constancy among the individual amino acids. 2. The concentrations of the free amino acids in sweat showed significant, individual variations. Particularly high excretion rates were observed in the following amino acids: alanine, glycine, citrulline, histidine, ornithine, threonine and serine. 3. As compared to men, women had an increased excretion of all the examined amino acids in sweat from the face, except for cystine. Statistically significant higher excretion was seen within this sex-specific comparison for the following amino acids: alanine, citrulline, glycine, histidine, isoleucine, serine, taurine, threonine, tyrosine and valine. 4. Essential amino acids such as isoleucine, leucine, lysine, methionine, phenylalanine and valine and also cystine were always excreted only in small amounts. 5. Significant differences were also observed in the total amino acid excretion and in the individual amino acid excretions in sweat obtained from different parts of the body of the same person. 6. The amino acid concentrations determined in the sweat from the face of the same individual at different times showed a relative constancy as compared to the large differences of the amino acid concentrations determined in the sweat from the face of different individuals.
Arch Dermatol Res 1975 Dec 10
PMID:[Free amino acids in human Eocrine sweat (author's transl)]. 76 10

Plasminogen is detected in the basal cell layer of the epidermis, keratinocytes can generate plasminogen activators and it is suggested that the generation of plasmin may facilitate keratinocyte division, migration and differentiation. In this study we have investigated the characteristics of plasminogen binding sites in normal human epidermis. It was found that 6-aminohexanoic acid and benzamidine displaced endogenous epidermal plasminogen from the basal layer suggesting that endogenous plasminogen binds initially via the kringle 5 aminohexyl (AH) site. Plasminogen binding sites in epidermis were further investigated by displacing endogenous plasminogen and incubating sections with exogenously added glu-plasminogen, lys-plasminogen and plasmin or the isolated plasminogen fragments kringles 1-3, kringle 4 and kringle 5L. The results suggest that the uptake of plasminogen involves primary interaction with the kringle 5AH site and a secondary interaction with lysine binding sites of kringles 1-3. Cell binding is not dependent upon additional reactions of the plasmin active centre.
Br J Dermatol 1992 Jan
PMID:Plasminogen binding sites in normal human skin. 131 Nov 89

The distribution of plasminogen/plasmin, the central proteolytic component of the plasminogen activator/plasmin system was analysed in lesional skin of bullous pemphigoid by using monoclonal antibodies (MAbs) specific for distinct epitopes of the plasminogen/plasmin molecule. Four groups of MAbs were used: (i) MAbs HD-PG 1 and HD-PG 2, specific for epitopes associated with the lysine-binding sites I (kringle domain 1 + 2 + 3) and II (kringle domain 4) of plasminogen/plasmin, (ii) MAbs HD-PG 6 and HD-PG 7, specific for the lysine binding site I only, (iii) MAbs HD-PG 12 (formerly designated P 2) and HD-PG 18, specific for non-kringle domains of glu- and lys-plasminogen, and (iv) MAb HD-PG 13 which recognizes glu-plasminogen, only. The basal cell layers of normal skin consistently reacted with MAb HD-PG 12, whereas only faint staining was seen with the other MAbs in the same biopsies. In contrast, all anti-plasminogen/plasmin MAbs strongly stained lower and intermediate epidermal cell layers of fully developed bullous pemphigoid lesions.
Br J Dermatol 1992 Sep
PMID:Enhanced association of plasminogen/plasmin with lesional epidermis of bullous pemphigoid. 139 Jan 72

The pathogenesis of Hailey-Hailey disease and Darier's disease was investigated using immunocytological and explant-tissue-culture techniques. There was breakdown of the intercellular adhesions between keratinocytes in explants from clinically uninvolved skin of patients with Hailey-Hailey disease or Darier's disease. The major desmosomal components were present in the cultures and were expressed in a punctate peripheral pattern at cell-cell contact sites, but there was diffuse staining of acantholytic cells. Plasminogen, which is expressed by basal keratinocytes in normal skin, was detected in association with suprabasal acantholytic cells in skin biopsies from these diseases. Plasminogen was reversibly displaced from the cells by 6-aminohexanoic acid, suggesting that binding is mediated by a reaction with the lysine receptor on the plasminogen molecule. Plasminogen was also detected in separating cells in explant cultures and there was cytoplasmic expression of the plasminogen activator urokinase by these cells. These abnormalities are not unique to either disease and do not account for the phenotypic differences between Darier's disease and Hailey-Hailey disease, but plasmin generation may have a role in perpetuating cell separation.
Br J Dermatol 1991 Nov
PMID:Cell adhesion in Hailey-Hailey disease and Darier's disease: immunocytological and explant-tissue-culture studies. 175 48

In order to get a better understanding of the role played by polyamines in calcium-induced epidermal cell differentiation, the time course of their metabolism was investigated. Results demonstrate that differentiating epidermal cells are characterized by time-dependent changes in polyamine concentrations. An early polyamine catabolic phase, characterized by increased total putrescine concentration and drastic reduction of both spermidine and spermine levels, is followed by active spermidine biosynthesis. The differences in putrescine and, in particular, spermidine metabolism are reflected in a time-dependent modulation of protein-bound polyamine derivatives. In fact, upon addition of calcium to the culture medium, hypusine N epsilon-(4-amino-2-hydroxybutyllysine) is rapidly reduced to undetectable levels. The very low hypusine level is paralleled by an increase in gamma-glutamyl putrescine derivatives and followed by a large increase in gamma-glutamyl spermidine derivatives; in addition, there is a remarkable concomitant biosynthesis of transglutaminase-catalyzed mono and bis gamma-glutamyl spermidine derivatives and epsilon(gamma-glutamyl)lysine cross-links. The effect of TPA and RA on hypusine formation is also reported.
J Invest Dermatol 1990 May
PMID:Polyamine-dependent post-translational modification of proteins in differentiating mouse epidermal cells. 210 18


1 2 3 4 5 6 7 8 9 10 Next >>