Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathways and kinetics of interchain disulfide bond formation have been determined in vitro for purified myeloma proteins representing the three major subclasses of mouse immunoglobulin G(IgG) using the reoxidation system described previously (Petersen, J.G.L. & Dorrington, K.J. (1974) J. Biol. Chem. 249, 5633-5641). Mixtures of oxidized and reduced glutathione were added to act as a disulfide interchange catalyst. The pathways of covalent assembly observed in vitro were qualitatively and quantitatively similar to those followed by the various subclasses in vivo. HH and HHL were the principle covalent intermediates seen with IgG1 (MOPC 31C) and IgG2a (MOPC 173 and clone 19). With IgG2b( MPC 11C), HL, HH and HHL were all prominant intermediates. The time courses of reoxidation were simulated using a theoretical model based on second-order reaction kinetics (Percy, J.R., Percy, M.E. & Dorrington, K.J. (1974) J. Biol. Chem. 250, 2398-2400). Two distinct phases were apparent in the reoxidation sequence. The first, which lasted for the initial 5-15 min, did not confirm to the theoretical model. The second phase could be accounted for by the model and represented the remainder of the covalent assembly process. The physico-chemical basis for this biphasic phenomenon was explored. Sedimentation velocity studies showed that noncovalent association was incomplete at the beginning of the reoxidation step for all proteins except IgG2b (MOPC 11C). No dissociation was apparent in the reduced and alkylated proteins at pH 5 in the absence of prior exposure to acid conditions. Thus, exposure to acid appears to affect the affinity between the subunits in the native proteins. Transfer of the proteins from pH 5 to pH 8.2 (the pH at which reoxidation proceeds) is accompanied by the generation of an absorption difference spectrum over an 8-10 min period. These data suggest that a pH-dependent conformational relaxation process may influence the early stages of reoxidation.
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PMID:Covalent assembly of mouse immunoglobulin G subclasses in vitro: application of a theoretical model for interchain disulfide bond formation. 95 49

A mathematical model, based on second-order reaction kinetics, has been used to describe the covalent assembly of immunoglobulin G(IgG) in vitro from its heavy (H) and light (L) chains (Percy, M.E., Baumal, R., Dorrington, K.J. & Percy, J. (1976) Can. J. Biochem. 54, 675-687). In the present paper, the same model has now been applied to the steady-state assembly of IgG in vivo. This mathematical approach permits a quantitative comparison of the pathways of covalent assembly used by given immunoglobulins in vivo and in vitro. The assumptions in the model are: the species L, H, HL, HH, HHL and LHHL belong to a common pool; incompleted IgG intermediates may freely assemble to form HL, HH, HHL and LHHL; the reaction rate for covalent linkage between any two reacting species is proportional to the products of the number densities of the reactants and to a parameter P which takes the value PHH if the reaction joins two H chains, and PHL if it joins an H and L chain. In vivo values of PHH/PHL were determined for the 18 mouse myeloma tumours and cell lines studied by Baumal et al. (Baumal, R., Potter, M. & Scharff, M. (1971) J. Exp. Med. 134, 1316-1334). From these analyses, we have arrived at the following conclusions: (1) the three major IgG subclasses have distinctive values of PHH/PHL (mean value 53 for IgG1, 12 for IgG2a and 2.8 for IgG2b); (2) for IgGs of the same subclass, the values of PHH/PHL are similar; (3) the mean in vivo values of PHH/PHL are very close to those determined from in vitro assembly experiments. Finally, the individual values of PHH/PHL have been used to simulate pulse-chase experiments in the various tumours and cell lines. Considering the sources and magnitude of experimental error, the theoretical pathways of assembly agree with those determined qualitatively from the pulse-chase experiments.
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PMID:Assembly of three major subclasses of mouse immunoglobulin G: a theoretical model for covalent assembly in vivo. 95 50

Acquisition of carbohydrates in the disulfide-linked heavy (H) and light (L) chain molecules of murine myeloma (ADJPC5), i.e., HH, HHL, and LHHL, was investigated. That some mannose and glucosamine residues are acquired by immunoglobulin precursor molecules was demonstrated by the detection of glucosamine and mannose in HH, HHL, and LHHL. In contrast, galactose was observed solely in LHHL molecules, which have an identical electrophoretic mobility to the secreted product. Furthermore, as judged from cells incubated with [(3)H]leucine, the more juvenile molecules HH and HHL were predominant in the rough microsome fraction, whereas LHHL was the principal molecular species in the smooth microsome fraction. Findings of this type were not observed in rabbit lymph node cells. Thus, galactose, as well as mannose and glucosamine, were found in the more juvenile molecule known for this species (HL). Moreover, the ratio of HL:LHHL, as judged from cells incubated with [(3)H]leucine, was about the same in rough and smooth microsomes.
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PMID:Synthesis and secretion of gammaglobulin by lymph node cells: the acquisition of carbohydrate residues of immunoglobulin in relation to interchain disulfide bond formation (heavy and light chains-murine myeloma-mannose-glucosamine-galactose). 410 96

Murine myeloma cells (ADJ-PC-5), incubated in vitro with (3)H-leucine, secrete (3)H-immunoglobulin G as a single molecular species as judged by the migration characteristics of the labeled product on sodium dodecyl sulfateacrylamide gel electrophoresis. However, the fact that some of the interchain disulfide linkages of intracellular immunoglobulins had not been acquired permitted the identification of the following intracellular species: LHHL (identical to immunoglobulin G), HHL, HH, and L (H and L refer to heavy and light polypeptide chains, respectively). Although HH and HHL were readily observed, radioactivity was not detected in the region of the gel where HL would be expected. The time course for the appearance of the intermediates indicates that in these cells the first interchain disulfide bond to be formed occurs between heavy chains. In contrast, the interchain disulfide bonds of immunoglobulins derived from rabbit lymph node cells were acquired in a different order. The principal intracellular species observed were LHHL and HL, whereas HHL and HH were not detectable. These findings indicate that in this species the first interchain disulfide bond to be formed is that between the heavy and light chains of immunoglobulin G.
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PMID:Synthesis and secretion of gamma-globulin by lymph node cells, VIII. Order of synthesis of the interchain disulfide linkages of immunoglobulins. 526 57