PubMed · 6917587
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
H P Sauerwein. 1982-02-16. [Hypocalcemia].. https://pubmed.ncbi.nlm.nih.gov/6917587/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Phosphatidylserine (PS)-containing membranes increase the kcat of the factor VIIIa-factor IXa enzyme complex by more than 1000-fold. While PS supports specific, high-affinity membrane binding of factor VIIIa and factor IXa, it is not known whether PS is the lipid that activates the membrane-bound complex. It is also not known whether PS or other activating lipids must reside in the two-dimensional membrane matrix for efficacy. We have found that submicellar concentrations of dihexanoic phosphatidylserine (C6PS) increase the activity of the factor VIIIa-factor IXa complex in a biphasic manner with half-maximal concentrations of 0.2 and 1.6 mM while the micelle-forming concentration is 4.0 mM. Increased cleavage of factor X at 0.25 mM C6PS was due to a 25-fold enhancement of the kcat and a 30-fold increase in the affinity of factor VIIIa for factor IXa. C6 phosphatidylethanolamine and C6 phosphatidic acid, but not C6 phosphatidylcholine, also accelerated the Xase complex, indicating that kcat enhancement has less structural specificity than membrane binding. Submicellar C6PS enhanced activity of factor IXa in the absence of factor VIIIa, but the effect was due to a decreased KM rather than an increased kcat. These results suggest that activation of the factor VIIIa-factor IXa complex can result from binding of individual C6PS molecules or small aggregates in the absence of a membrane bilayer. They provide a model system in which the phospholipid-induced activation may be distinguished from membrane-binding of the enzyme complex.
At the molecular level, our knowledge of the low voltage-activated Ca2+ channel (T-type) has made little progress. Using an antisense strategy, we investigated the possibility that the T-type channels have a structure similar to high voltage-activated Ca2+ channels. It is assumed that high voltage-activated channels are made of at least three components: a pore forming alpha1 subunit combined with a cytoplasmic modulatory beta subunit and a primarily extracellular alpha2delta subunit. We have examined the effect of transfecting cranial primary sensory neurons with generic anti-beta antisense oligonucleotides. We show that in this cell type, blocking expression of all known beta gene products does not affect T-type current, although it greatly decreases the current amplitude of high voltage-activated channels and modifies their voltage dependence. This suggests that beta subunits are likely not constitutive of T-type Ca2+ channels in this cell type.
Explore the source record for details and available documents.