Biomaterial Database

Role of polyglutamates in methotrexate action. 1985

W Wilmanns, and A Schalhorn

Numerous cell systems and tissues contain methotrexate (MTX) polyglutamates after MTX and HDMTX (high dose) treatment. The formation of MTX polyglutamates is concentration- and time-dependent. Great differences in the length of the poly-y-glutamyl side chains are observed. Efflux kinetics of MTX and MTX polyglutamates vary considerably depending on the kind of cells and the length of the side chain. In erythrocytes accumulation of MTX and MTX polyglutamates results in intracellular concentrations much higher than the serum MTX levels. Efflux differences with long-lasting storage of the polyglutamate forms of MTX up to the total life-span of the single erythrocyte. Even 6-14 days after HDMTX therapy, high MTX levels could be determined in sarcoma tissue. In each case besides unchanged MTX there was a formation of MTX polyglutamates. The portion of polyglutamates varied considerably, amounting from 3% to 68% of total tumor MTX. A relation between the formation of MTX polyglutamates and the clinical effectiveness of HDMTX therapy seems to be possible. MTX polyglutamates play a major role in the principles and effectiveness of HDMTX therapy.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D011099	Polyglutamic Acid	A peptide that is a homopolymer of glutamic acid.	Polyglutamate
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012509	Sarcoma	A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.	Sarcoma, Epithelioid,Sarcoma, Soft Tissue,Sarcoma, Spindle Cell,Epithelioid Sarcoma,Epithelioid Sarcomas,Sarcomas,Sarcomas, Epithelioid,Sarcomas, Soft Tissue,Sarcomas, Spindle Cell,Soft Tissue Sarcoma,Soft Tissue Sarcomas,Spindle Cell Sarcoma,Spindle Cell Sarcomas
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor