Receptors differences from enzymes

It is very important to realise that when drugs or medicines are administered to the body there is the opportunity for chiral interactions. This is because the human body is composed of enzymes and receptors that are protein in nature. These proteins are polymers of 20 or so naturally occurring amino acids. With the exception of glycine, all of these amino acids are chiral (all are L-series amino acids - see later) and it must be expected that a chiral drug will interact with these chiral receptors differently from its enantiomer. It is often the case that if a racemic mixture of a chiral drug is administered, only one enantiomer will be active, while the other will be... 

Uncompetitive antagonism, form of inhibition (originally defined for enzyme kinetics) in which both the maximal asymptotic value of the response and the equilibrium dissociation constant of the activator (i.e., agonist) are reduced by the antagonist. This differs from noncompetitive antagonism where the affinity of the receptor for the activating drug is not altered. Uncompetitive effects can occur due to allosteric modulation of receptor activity by an allosteric modulator (see Chapter 6.4). 

Each cell is surrounded by a plasma membrane that separates the cytoplasmic contents of the cell, or the intracellular fluid, from the fluid outside the cell, the extracellular fluid. An important homeostatic function of this plasma membrane is to serve as a permeability barrier that insulates or protects the cytoplasm from immediate changes in the surrounding environment. Furthermore, it allows the cell to maintain a cytoplasmic composition very different from that of the extracellular fluid the functions of neurons and muscle cells depend on this difference. The plasma membrane also contains many enzymes and other components such as antigens and receptors that allow cells to interact with other cells, neurotransmitters, blood-borne substances such as hormones, and various other chemical substances, such as drugs. 

Once synthesized, NO behaves somewhat differently from classical neurotransmitters. NO is not released from neurons in a Ca +-dependent exocytotic process rather, it diffuses freely out of the neuron and to the next neuron. Once it reaches its target enzyme, NO does not interact with specific membrane-associated receptor proteins instead, it interacts with second-messenger molecules in the receiving neuron... 

In the second step the bas is recognized by the receptor site and the bas-rep complex forms. As was noted above, the complex is generally bonded by inter-molecular forces. The bas is transferred from an aqueous phase to the receptor site. The receptor site is very much more hydrophobic than is the aqueous phase. It follows, then, that complex formation depends on the difference in intermolecular forces between the bas-aqueous phase and the bas-receptor site. The importance of a good fit between bas and receptor site has been known for many years. The configuration and conformation of the bas can be of enormous importance. Also important is the nature of the receptor. If the receptor is. a cleft, as is the case in some enzymes, steric effects may be maximal as it may not be possible for a substituent to relieve steric strain by rotating into a more favorable conformation. In such a system, more than one steric parameter will very likely be required in order to account for steric effects in different directions. Alternatively, the receptor may resemble a bowl, or a shallow, fairly flat-bottomed dish. Conceivably it may also be a mound. In a bowl or dish, steric effects are likely to be very different from those in a cleft. Possible examples are shown in Fig. 1, 2, and 3. 

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