Neurochemistry

The synthesis of ACh from choline and acctyl-CoA is catalyzed by Ch AT, Transfer of the acetyl group from acetyl-CoA to choline may be by a random or an ordered reaction of the Theorell-Chance type. In (he ordered sequence, acetyl-CoA first binds to the enzyme, forming a complex (EA) (hat then binds to choline. Tlie acetyl group is transferred, and the ACh formed dissociates from the enzyme active site. The CoA is then released from the enzyme complex. EQ. 

After ACh has been released into (he synaptic cleft, ih concentration decreases rapidly. It is generally accepted tha there is enough AChE at nerve endings to hydrolyze ink choline and acetate any ACh (hat has been liberated. F example, (here is sufficient AChE in the nerve junction ol rat intercostal muscle to hydrolyze about 2.7 X 10 AD molecules in I millisecond (his far exceeds (he 3 x l(f molecules released by one nerve impulse.  

TABLE 17-2 Conformational Properties of Some Cholinergic Agents  

MtHiin. J. F unil Riiriuiril. F A (cds.) Cliit incr( ii Lip tiid ImmHMinns New YtHl. AcaJcntic PrcM, 1971, pp. K7 K9. 

Molecular orbital calculations based on the principles of quantum mechanics may be used to detennine energy minima of rotating bonds and to predict preferred conformations for the molecule. By means of molecular mechanics, theoretical contbrmational analysis has found that ACh has an energy minimum for the tz torsion angle at about 84° and that the preferred confimnation of ACh corresponds clo.sely in ttqueous solution to that found in the crystal stale. 

Barkan, Diana (1999). Walther Nemst and the Transition to Modem Physical Science. Cambridge, U.K. Cambridge University Press. 

Hiebert, Erwin N. (1978). Nernst, Hermann Walther. In Dictionary of Scientific Biography, Vol. XV, Supplement I, ed. Charles C. GiUispie. New York Scribners. 

Mendelssohn, Kurt (1973). The World of Walther Nemst The Rise and Fall of German Science. London Macmillan. 

Neurochemistiy refers to the chemical processes that occur in the brain and nervous system. The fact that one can read this text, remember what has been read, and even breathe during the entire time that these events take place rehes on the amazing chemistry that occurs in the human brain and the nerve cells with which it communicates. 

Like any other cell, a nerve cell has a membrane as its outer wall. On the outside of the membrane, the concentration of sodium ions will be relatively high and that of potassium ions will be relatively low. The membrane maintains this concentration gradient by using channels and enzymes. 

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G. J. Siegel and co-workers, Basic Neurochemistry, 5th ed.. Raven Press, New York, 1994. 

Edwards, C. In Neurotoxins as Tools in Neurochemistry, Dolly, J. O. Ellis Hor-wood Limited Chichester, England, 1988, pp. 219-240. 

Stocchetti N, Protti A, Lattuada M, Magnoni S, Longhi L, Ghisoni L, Egidi M, Zanier ER. Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury. J Neurol Neurosurg Psych 2005 76(8) 1135-1139. 

The sites of action of drugs affecting the dopamine synapse are indicated in Fig. 7.3. Those modifying the synthesis, storage, release, uptake and metabolism of DA have been covered above in the appropriate sections on neurochemistry. The actions and uses of agonists and antagonists are outlined in Table 7.4 and covered in detail in appropriate chapters. Their structures are given in Fig. 7.6. 

Hough, LS and Green, JP (1983) Histamine and its receptors in the nervous system. In Handbook of Neurochemistry (Ed. Lajtha, A), Vol6, Plenum Press, New York, pp. 187-211. 

There is no evidence of a general overactivity in DA function in schizophrenic patients. Plasma prolactin is not reduced, so the DA inhibitory control of its release is normal there is no recorded increase in DA turnover as CSF and plasma levels of its major metabolite HVA are normal and dyskinesias, which would reflect increased DA activity, are rare. PM studies have shown no consistent increases in DA brain levels, although some reports show an increase in the left amygdala, or in the activity of enzymes involved in its synthesis (tyrosine hydroxylase) or metabolism (MAO). For a review of the neurochemistry see Reynolds (1995). 

Horton, RW (1992) The neurochemistry of depression evidence derived from studies of postmortem brain tissue. Molec. Aspects Med. 13 191-203. 

Van Riezen, H and Leonard, BE (1990) Effects of psychotropic drugs on the behaviour and neurochemistry of olfactory bulbectomised rats. Pharmac. Ther. 47 21-34. 

Another way of viewing it would be as levers going off Serotonin is inhibitory, dopamine is excitatory. That is naive, but there is evidence to suggest that in the neurochemistry of those compounds there has been a kind of yin and yang. 

There are several ways in which possible neurotoxic effects might be studied. First, measurement of cerebrospinal fluid concentrations of dopamine or serotonin metabolites would be a straightforward way of assessing neurotoxicity. There are pitfalls in this approach (as outlined by Dr. Ricaurte (this volume), such as the facts that lumbar cerebrospinal fluid might reflect spinal cord neurochemistry more than it reflected brain neurochemistry, and drugs like /r-chloroamphetamine affect serotonin neurons in spinal cord less than they do those in brain (Sanders-Bush... 

Roth SH, Skrajny B, Reiffenstein RJ. 1995. Alteration of the morphology and neurochemistry of the developing mammalian nervous system by hydrogen sulphide. Clin Exp Pharmacol Physiol 22 379-380. 

Neurochemistry of Sleep and Wakefulness, ed. J. M. Monti et al. Published by Cambridge University Press. Cambridge University Press 2008. 

An excellent description of the discovery of neurotransmitters is provided by Valenstein (2005). Only the essentials of neurotransmitter metabolism are covered here for more detailed information the reader is directed to textbooks of neurochemistry, e.g. Siegel et al. (1994). For a more advanced coverage of the topics discussed here as well as information on the electrical properties of the neurons involved, the interested reader is directed to Steriade McCarley (2005). 

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