Latent mechanical activation

Hyperthyroidism, peptic ulcer, latent or active bronchial asthma, mechanical GI and urinary obstruction or recent GI resection, acute inflammatory GI tract conditions, anastomosis, bladder wall instability, pronounced bradycardia, hypotension, hypertension, cardiac disease, coronary artery disease, vasomotor instability, epilepsy, Parkinsonism. 

In viw PAI and antithrombin are stabilized in their active forms by binding to vitronectin and heparin, respectively. These two serpins seem to have evolved what Max Perutz has called "a spring-loaded safety catch" mechanism that makes them revert to their latent, stable, inactive form unless the catch is kept in a loaded position by another molecule. Only when the safety catch is in the loaded position is the flexible loop of these serpins exposed and ready for action otherwise it snaps back and is buried inside the protein. This remarkable biological control mechanism is achieved by the flexibility that is inherent in protein structures. 

Suicide substrates and quiescent affinity labels, unlike the other types of inhibitors discussed in this chapter, form covalent bonds with active site nucleophiles and thereby irreversibly inactivate their target enzymes. A suicide substrate,191 also described by Silverman in a comprehensive review1101 as a mechanism-based inactivator, is a molecule that resembles its target enzyme s true substrate but contains a latent (relatively unreactive) electrophile. When the target enzyme attempts to turn over the... 

The amount of total enzymatic activity that becomes manifest only after disruption of membranous barriers between enzyme and substrate or upon removal of some otherwise inhibitory factor. Membrane disruption is often achieved by treatment with detergent to solubihze the enzyme. One example is the so-called microsomal glucose-6-phosphatase, an enzymatic activity that is located in the lumen of the endoplasmic reticulum but becomes trapped as a latent activity in microsome vesicles upon mechanical disruption of cells. 

Infections Corticosteroids may mask signs of infection, and new infections may appear during their use. There may be decreased resistance and inability of the host defense mechanisms to prevent dissemination of the infection. Restrict use in active tuberculosis to cases of fulminating or disseminated disease in which the corticosteroid is used for disease management with appropriate chemotherapy. Corticosteroids may exacerbate systemic fungal infections and may activate latent amebiasis. 

Latent pacemakers (cells that show slow phase 4 depolarization even under normal conditions, eg, some Purkinje fibers) are particularly prone to acceleration by the above mechanisms. However, all cardiac cells, including normally quiescent atrial and ventricular cells, may show repetitive pacemaker activity when depolarized under appropriate conditions, especially if hypokalemia is also present. 

The first true latent inhibitor for ADH (i.e. an inhibitor produced by the catalytic act of the enzyme that is time dependent) was reported as being the substituted allyl alcohol, 3-ethylthioprop-2-en-l-ol.1428 This is a substrate for LADH, but after a short period the enzyme loses its activity, the rate of deactivation being proportional to the concentration of the alcohol. Latent inhibition was confirmed by showing directly that the aldehyde is an inhibitor. A mechanism is proposed in which the aldehyde formed reacts with an unspecified nucleophilic site on the enzyme with subsequent protonation.1429... 

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