C-pathway

The protein-C pathway is one of the most important anticoagulant mechanisms. It is activated by thrombin. Thrombin binds to a cofactor in the membrane of endothelial cells, thrombomodulin (TM). TM bound thrombin no longer activates clotting factors or platelets but becomes an effective protein C (PC) activator. Activated PC (APC) forms a complex with Protein S, which inactivates FVIIIa and FVa. Hereby generation of Flla by the prothrombinase complex is inhibited (Fig. 9). Thus, the PC-pathway controls thrombin generation in a negative feedback manner. 

Cary MP, Bader GD, Sander C. Pathway information for systems biology. FEES Lett 2005 579 1815-20. 

These experiments demonstrate that the surface-catalyzed 2 reaction is far more effident than either the or C pathway for the dehydrative coupling of alcohols over the solid add catalysts tested. High selectivity to configurationally inverted chiral ethers ensues, espedally in the case of the HZSM-5 catalyst, in which the minor C or C paths were further suppressed by "bottling" of 3-ethoxypentane by the narrow zeolite chaimels. 

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

Fig. 7. Our current understanding of the protein C pathway. V, and VIII, represent inactivated factors V and VIII, respectively. For an explanation of other abbreviations see text.

Dahlback, A. and Villotreix, B. 2005. The anticoagulant protein C pathway. FEBS Letters 579(15), 3310-3316. 

Thus, the 1,2-C pathway dominates when 84 is generated by the thermolysis of a tosylhydrazone salt, but a 1,2-H shift to cyclopropylethene is the major pathway when 84 is generated from either a hydrocarbon precursor or via the atomic carbon abstraction of oxygen from cyclopropylmethylketone at —196°C.U1... 

Perroy, J., Prezeau, L. M. D. W., Shigemoto, R Bockaert, J., and Fagni, L. (2000) Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. J. Neurosci. 20,7896-7904. 

Fig. 9.1. Simplified reaction mechanisms in the hydrolytic decomposition of organic nitrates. Pathway a Solvolytic reaction (Reaction a) with formation of a carbonium ion, which subsequently undergoes SN1 addition of a nucleophile (e.g., HO ) (Reaction b) or proton E1 elimination to form an olefin (Reaction c). Pathway b HO -catalyzed hydrolysis (,SN2). Pathway c The bimolecular carbonyl-elimination reaction, as catalyzed by a strong base (e.g., HO or RO ), which forms a carbonyl derivative and nitrite.

Arylindenes undergo sigmatropic 1,5-shifts, induced oxidatively [267], thermally [268], photochemically [269], and re-ductively [270]. The reductive rearrangement of 1,1,3-triphenylindene, yielding the dianion of l,2,3-triphenyl-2H-indene, has been the subject of voltammetric investigations in DMF-TBAP [271]. The reaction follows an EEC or EDisp C pathway. 

Blumberg PM (1991) Complexities of the protein kinase C pathway Mol Carcinog 4 339-344... 

Aliphatic and aromatic thiols react with pyridine 1-oxides and their quaternary derivatives by Type A, B and/or C pathways, but no such reactions have been reported for pyridine or its salts. 1-Ethoxypyridinium ethosulfate reacts with sodium n-propanethiolate to give mainly pyridine (Type A), and a 6 1 mixture of 3- and 4-pyridyl propyl sulfides (equation... 

Given the advantages of the -pathway for H-atom abstraction mentioned above, it seems sensible to ask whether a c-pathway could be operative on the triplet surface as well. This possibility was explored for model iron(IV)-oxo complexes involving... 

J(C, Q couplings through C pathway were studied, both experimentally and theoretically, in carbohydrates 93 and a Karplus-like relationship... 

There has been a tendency to call both the E and C pathways as Type II or Norrish II reactions since it is well established that they emanate from common intermediates. Wagner has suggested that the C pathway be called more appropriately the Yang reaction [255]. Whether this is followed will depend upon the tolerance of photochemists for the proliferation of name reactions. We group the two processes together while recognizing the fundamental work of Yang. 

Rodriguez A., Freixes M., Dalfo E., Martin M., Puig B., and Ferrer I. (2005). Metabotropic glutamate receptor phospholipase C pathway A vulnerable target to Creutzfeldt-Jakob disease in the cerebral cortex. Neuroscience 131 825-832. 

Ni YG, Panicker MM, Miledi R. Efficient coupling of 5-HTla receptors to the phospholipase C pathway in Xenopus oocytes. Brain Res Mol Brain Res 1997 51 115-122. 

Both intracellular release and transmembrane flux contribute to the rise in intracellular Ca2+.14,15 The rise in keratinocyte intracellular Ca2+ in response to raised extracellular Ca2+ has two phases (a) an initial peak, not dependent on extracellular Ca2+ and (b) a later phase that requires extracellular Ca2+.14 An early response of human keratinocytes to increases in extracellular Ca2+ is an acute increase in intracellular Ca2+. Stepwise addition of extracellular Ca2+ to neonatal human keratinocytes is followed by a progressive increase in intracellular Ca2+, where the initial spike of increased intracellular Ca2+ is followed by a prolonged plateau of higher intracellular Ca2+.16 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes is saturated at 2.0 mM extracellular Ca2+.16,17 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes resembles the response in parathyroid cells, in that a rapid and transient increase in intracellular Ca2+ is followed by a sustained increase in intracellular Ca2+ above basal level. This multiphasic response is attributed to an initial release of Ca2+ from intracellular stores followed by an increased influx of Ca2+ through voltage-independent cation channels. The keratinocyte and parathyroid cell contains a similar cell membrane calcium receptor thought to mediate this response to extracellular Ca2+. This receptor can activate the phospholipase-C pathway, leading to an increase... 

Pathways (a)-(b)-(c)-(d) and (a )—(b )—(c )—(d ) correspond to the original mechanism proposed by Cossee [268,276,277] and are still valid, apart from some minor modifications [1], for heterogeneous catalysts. For metallocene-based catalysts of classes II and partially V, this mechanism gives rise to successive additions at the same site (from a configurational point of view) and is known as the chain stationary insertion mechanism ( chain skipped insertion or site isomerisation without insertion mechanism) [143, 146, 345], The (a)-(b)-(c)-(a )—(b )—(c ) pathway corresponds to the chain migratory insertion mechanism found in the case of metallocene catalysts of classes I, III, IV and partially V [143, 146]. 

Pathways B and C describe the process that could occur to form the symmetrical silyl ketal. Formation of silyl ketal-metal complex VII could occur in one step via an associated pathway B, or in two steps via a dissociative pathway C. Pathway B could occur by attack on the pentacoordinated silyl ketal-metal complex IV by alcohol ROH, forcing the dissociation R OH leading to complex VII. The associative pathway would precede through a hexacoordinated silicon species. Hexacoordinated silicon compounds have been shown to be very reactive.36,23d The choice of the alcohol that dissociates would be determined by electronic and/or steric factors. 

As a result of the action of IP3, [Ca2+], is increased, i.e., the calcium signal is generated. The other product of PIP2 hydrolysis, DG, has been shown to activate a protein kinase (protein kinase C) [8], The DG/protein kinase C pathway appears to function in the modulation of the calcium signal. Protein kinase can phospho-rylate and activate the 5-phosphomonoesterase thereby lowering the IP3 concentration and subsequently decreasing the intracellular free calcium concentration. 

---