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at what pH is insulin a monomer
below pH 2, with low concentration
at what pH does dimerisation and complex formation with zinc occur?
above pH4
what interaction allow the insulin to form a hexamer?
electrostatic attraction between glutamic acid and lysine, and the hydrophobic interaction between alpha helix
how does lispro decrease its duration of action as a short acting insulin?
changing lysine to proline which is a cyclic amino acid which causes the protein chain to chnage direction so there is no electrostatic attraction, so dimer is not formed. the insulin goes from a hexamer straight to a monomer.
how does aspart- novolog work as a fast acting insulin?
aspartic acid instead of proline which results in a negative charge on both chains, so there is no electrostatic interaction, so dimer formation does not occur
how is glulisine a fast acting inusline
replacing the lysine with a glutamic acid, which results in a negative negative charge, so dimer does not form
how does lantus act as a basal insuline?
changing the isoelectric point results in perciptaion when injected, which slowly dilutes to monomers which binds to albumin and are slowly released.
how does detemir act as a long acting insulin?
has a lipid moiety which slows absorption, and can also bind to albumin
what conformational chnage does the insulin hexamer go through when bound to phenol?
from tense to relaxed
how does tresiba/degludec act as a longer acting insulin?
injected as a stable soluble dihexmer, phenol dissociates to give a tense structure froming a multihexamer of insulin,which then dimerises then monomerises. the monomers can then bind to albumin and are slowley released
what is essential in the structure of tresiba/degludec?
Terminal COOH of the fatty acid chain