Enzyme inhibition/inhibitors specificity

The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form. 

Enzyme inhibitors are chemicals that may serve as a natural means of controlling metabolic activity by reducing the number of enzyme molecules available for catalysis. In many cases, natural or synthetic inhibitors have allowed us to unravel the pathways and mechanisms of intermediary metabolism. Enzyme inhibitors may also be used as pesticides or drugs. Such materials are designed so that they inhibit a specific enzyme that is peculiar to an organism or a disease state. For example, a good antibiotic may inhibit a bacterial enzyme, but it should have no effect on the host person or animal. 

GABA synthesis inhibitors act on the enzymes involved in the decarboxylation and transamination of GABA. Glutamic acid decarboxylase (GAD), the first enzyme in GABA biosynthesis, is inhibited easily by carbonyl reagents such as hydrazines [e.g., hydrazinopropionic acid (4.164) or isonicotinic acid hydrazide (4.165)], which trap pyridoxal, the essential cofactor of the enzyme. A more specific inhibitor is allylglycine (4.166). All of these compounds cause seizures and convulsions because they decrease the concentration of GABA. 

This imperfect binding specificity principle also helps us to understand why chemicals called competitive inhibitors may block the active sites of enzymes. These inhibitors are structurally like the enzyme s appropriate substrate, enabling them to bind. But these compounds may be somewhat, or even completely, unreactive. Such enzyme inhibition appears to explain the limited microbial dehalogenation of 3-chlorobenzoate in the presence of 3,5-dichlorobenzoate (Suflita et al., 1983). In this case, 3,5-dichlorobenzoate is initially transformed to 3-chlorobenzoate ... 

Ornithine decarboxylase is specifically inhibited by the enzyme-activated inhibitor a-difluoromethyl-ornithine, which can cure human infection with Trypanosoma brucei (African sleeping sickness) by interfering with polyamine synthesis.243-2443 In combination with inhibitors of spermidine synthase or S-adenosylmethionine decarboxylase,245 it can reduce polyamine levels and growth rates of cells. Another powerful inhibitor that acts on both ornithine and adenosylmethionine decarboxylases is the hydroxy-lamine derivative l-aminooxy-3-aminopropane 246... 

Efavirenz is a nonnucleoside reverse transcriptase inhibitor specific for HIV-1. After binding to a site distant from the active site on the HIV-1 reverse transcriptase, it disrupts catalytic activity of the enzyme by causing a conformational change and does not compete with deoxynucleoside triphosphates. Efavirenz does not inhibit HIV-2 reverse transcriptase and human DNA polymerases a, (3, 7 and 8. The resistance to the drug develops rapidly from site-directed mutagenesis specifically at codon 103, and also at codons 100, 106, 108, 181, 190 and 225 of viral reverse transcriptase. This resistance will be applicable for all nonnucleoside transcriptase inhibitors. 

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