P-type pathway

Figure 6.9. Sequences for the gradient-selected HMQC experiment. Sequence (a) is suitable for the collection of absolute-value data. Sequence (b) provides phase-sensitive data via the echo-antiecho procedure. The N- and P-type pathways are selected with the last gradient whilst the first two gradients are placed within spin-echoes to refocus shift evolution.

Figure 6.10. A gradient-selected, phase-sensitive HSQC sequence using the echo-antiecho approach. The N- and P-type pathways are selected by the last gradient.

Figure 9.35. The COSY-IDOSY sequence. The gradient pulses select for the conventional N-type COSY pathway in addition to providing diffusion encoding (selection of the P-type pathway would use gradient pulses of opposite sign).

Acid chlorides, RCOCl, undergo ready attack by weaker nucleophiles, e.g. H2O, ROH. The question then arises whether, with the better potential leaving group Cl , the reactions of acid chlorides could proceed either via a single step 8 2 type pathway (cf. p. 78) involving a T.S., in which attack by and loss of Q are essentially synchronous or via an 8 1 type pathway (cf. p. 79) in which the slow step is RCOCl RCO Cl , followed by fast attack by Y on the acyl cation, RCO . In fact, most reactions of acid chlorides probably proceed via the now familiar tetrahedral intermediate pathway, though there may be some exceptions. 

A relatively small minority of APP molecules enter the p-secretase pathway in which p-secretase cleaves APP and releases a soluble fragment, sAPPp. The C-terminal membrane-bound C99 peptide is then cleaved by y-secretase within the transmembrane domain, and two major isoforms of 40 and 42 amino acid lengths with different C-termini, Ap40 and Ap42, are generated. Based on the amino acid sequence, p-secretase is predicted to be a type I transmembrane protein with the active site on the lumenal side of... 

An H+ electrochemical gradient (ApH+) provides the energy required for active transport of all classical neurotransmitters into synaptic vesicles. The Mg2+-dependent vacuolar-type H+-ATPase (V-ATPase) that produces this gradient resides on internal membranes of the secretory pathway, in particular endosomes and lysosomes (vacuole in yeast) as well as secretory vesicles (Figure 3). In terms of both structure and function, this pump resembles the F-type ATPases of bacteria, mitochondria and chloroplasts, and differs from the P-type ATPases expressed at the plasma membrane of mammalian cells (e.g., the Na+/K+-, gastric H+/K+-and muscle Ca2+-ATPases) (Forgac, 1989 Nelson, 1992). The vacuolar and F0F1... 

Presynaptic H3 receptors also are uniform in their signal transduction. They couple to Gi/o proteins and decrease the depolarization-induced release of neurotransmitters by inhibiting multiple calcium channels (e.g., Arrang et al. 1985 Schlicker et al. 1994 Endou et al. 1994 Brown and Haas 1999 see Stark et al. 2004). For comparison, the signal transduction of soma-dendritic H3 autoreceptors in histamin-ergic neurons also involves a pertussis toxin-sensitive G-protein with subsequent inhibition of N- and P-type Ca2+ channels (Takeshita et al. 1998). The few exceptions to this signal transduction pathway are discussed in the corresponding subsections below (see Sections 3.1, 3.3, and 3.9). 

Fig. 2 Mechanisms involved in presynaptic facilitation through A2 adenosine receptors. A2A and A2B adenosine receptors (A2aAR, A2B AR), by coupling to Gs, activate adenylate cyclase and protein kinase A (PKA). This may (1) influence SNARE proteins or (2) enhance calcium currents through P-type voltage-sensitive calcium channels (P-VSCC). A2aAR may also couple to Gq, leading to activation of a protein kinase C (PKC) pathway. This may (3) enhance calcium currents through N-VSCC, (4) influence SNARE proteins, (5) promote the PKA pathways or (6) remove an ongoing Gj/0 mediated inhibition of release.

Hydroxybenzaldehydes react with alkyl vinyl ketones in the presence of l,4-diazabicyclo[2.2.2]octane (DABCO) to yield 3-acyl-277-chromenes (Scheme 19) <2000J(P 1)1331 >. The reaction proceeds via a Baylis-Hillman type pathway to form the zwitterionic intermediate 61 with subsequent cyclization and dehydration to afford 2-acyl-2H-chromenes (Scheme 19) <20030BC1133>. 

Glycosylamines were shown efficient stereodifferentiating templates in the synthesis of enantiomerically pure P-amino acids. They react with silylketene acetals and zinc(II) chloride as the promoting Lewis acid via a Mannich-type pathway to give P-amino acid esters 12 in high yields and high diastereoselectivity [26], (Scheme 9). 

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