Block 2 Lecture 25 Flashcards
what causes a change in the rate of reaction
either the maximum velocity (Jmax) or the affinity of the protein for its substrate (Kt) or both
when would Jmax change
when the number of transporters change but can also sometimes be caused by changing the turnover number
what would cause Jmax to increase
if more proteins are synthesized
what is the turnover number of proteins
how rapidly proteins undergo the conformational changes associates with moving substrate across the membrane
what causes a change in Kt
affinity of an enzyme for its substrate changing or the protein structure changing
what happens when transport proteins are occupied at a low concentration of substrate
the transport protein has a high affinity for the substrate
what are the two basic strategies for responding to a change in the environment
- a long term response-involves making more or less of the proteins required to deal with the change (hours to days)
- a short term response- modifying the activity of an existing protein to make them go faster or slower (seconds to minutes)
what do cells use in short term responses
post translational modification (PTM)
what are the 2 basic PTM strategies
- modify the structure of a protein- influencing how well it works under current conditions of the cell
- change the location of the protein- exposing it to more or less of the reactant with which its supposed to work
What does modifying the structure in PTM entail
non-covalent binding of a protein to something (Ca2+, GTP, or another protein), or addition/ removal of a phosphate group, or removing a portion of the proteins amino acid sequence
what happens with Ca2+ binding in PTM
- under normal physiological conditions, PMCA mediated Ca2+ efflux occurs at a low rate because Ca2+ is low and because Kt for Ca2+ is high (affinity is low)
- when Ca2+ rises, PMCA cannot bring [Ca2+] back to normal by itself. calmodulin is a calcium binding protein that binds to Ca2+ and changes its conformation and permits it to bind to PMCA. the PMCA/Calmodulin complex has a higher affinity for Ca2+ than PMCA does by itself so efflux of Ca2+ increases
what happens in the phosphatidylinositol signal pathway in PTM strategy 1
- secretagogues bind to GPCR
- that protein activates phospholipase C which converts a membrane phospholipid to DAG and IP3
- DAG binds to and activates PKC
- PKC phosphorylates proteins including Rab (involved in SSC)
- Rab activates v-SNAREs and t-SNAREs that result in release of zymogens
- IP3 binds to and activates a Ca2+ channel in the ER reeleasing Ca2+ into cytoplasm which binds to proteins like synaptotagmin which stimulates v-SNAREs and t-SNAREs that stimulates release of zymogens
what are examples of PTM strategy 2 (change in location)
- GLUT4 transporter that transport glucose from blood, Rab proteins place the fully competent transporters into a location where they can do their job
- endocytic receptor down regulation- the conformational change that certain receptors undergo following binding of a ligand results in aggregation in the membrane and internalization via endocytosis which makes the receptor inactive
what happens in PDZ based regulation
-PDZ adapter proteins have 2 or more PDZ domains where a PDZ ligand can bind. it brings proteins close together the influence each others activity with much greater efficiency than if the proteins were to come in contact by facilitated diffusion
where are PDZ ligands found
at the c-terminal end of many transport proteins
