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• W1517505529 endingPage "226" @default.
• W1517505529 startingPage "217" @default.
• W1517505529 abstract "A general route for protein synthesis in eukaryotic cells has been proposed and applied to monoclonal antibody (MAb) synthesis. It takes into account transcription of the gene, binding of ribosomes to mRNA, and polypeptide elongation including binding to SRP (signal recognition particles) and SRP-receptor, competing translocation, folding and glycosylation, assembly of the heavy and light chains in a tetrameric protein and Golgi processing and secretion. A comprehensive model was built on the basis of the proposed pathway. The model takes into account the mechanism of each step. Metabolic control analysis (MCA) principles were applied to the general pathway using the proposed model, and control coefficients were calculated. The results show a shared flux control (of both pathway flux and flux ratio at the branch) among different steps, i.e., transcription, folding, glycosylation, translocation and building blocks synthesis. The steps sharing the control depend on the concentration of building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP (heavy chain binding protein) and PDI (protein disulfide isomerase). Model predictions compare well with experimental data for MAb synthesis, explaining the control structure of the route and the heterogeneity of the product and also addressing future targets for improvement of the production rate of MAbs." @default.
• W1517505529 created "2016-06-24" @default.
• W1517505529 creator A5050831739 @default.
• W1517505529 creator A5055040873 @default.
• W1517505529 creator A5069731582 @default.
• W1517505529 date "2001-01-01" @default.
• W1517505529 modified "2023-10-10" @default.
• W1517505529 title "Metabolic Control Analysis of Monoclonal Antibody Synthesis" @default.
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• W1517505529 doi "https://doi.org/10.1021/bp000165b" @default.
• W1517505529 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11312697" @default.
• W1517505529 hasPublicationYear "2001" @default.
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