Frontiers in Enzyme Inhibition

Enzyme inhibitors alter the activity of an enzyme molecule when an enzyme binds to it. The enzyme inhibition finds its applications in drug discovery and assessment of various environmental pollutants owing to its high specificity and potency. The study of enzyme inhibition mechanism is highly recommended as it mainly depends upon the structural requirement and site of enzyme action. The enzyme inhibition also plays a vital role in the design of biosensors for the detection and assessment of an analyte molecule.

Enzyme is a protein fragment that catalyzes the biological reactions by reducing the activation energy required for the reactions to occur. Enzyme inhibition is a vital method for regulating movement in living cells. Enzyme inhibition occurs by the substrate called inhibitors that can bind to an enzyme and reduce its activity, endogenous mixes and xenobiotics are compound. There are three fundamental kinds of enzyme inhibition: competitive, non-competitive, and uncompetitive. Among the measuring time frame, enzyme repressing drugs are anticipated to be presented for new signs including asthma and interminable obstructive pneumonic ailment, aspiratory blood vessel hypertension, hepatitis C and discontinuous claudication. This chapter offers an expansive point by point diagram of compound inhibitors at present available and those in late-organize medical trials. The data and examination exhibited in this report are vital resources in basic leadership for chiefs engaged with business advancement, advertising, statistical surveying, item improvement, mergers, and acquisitions, authorizing, business administration, speculation managing an account and arrangement creation, and to specialists to the pharmacological and biotechnology industry. The investigation gives a complete examination of the present markets for compound hindering medications and, specifically, the market capability of promising medications and innovations a work in progress.

An enzyme biosensor is an investigative device that joins an enzyme with a transducer to create a signal corresponding to target analyte fixation. An ideal enzyme activity is a basis for the maintenance of physiological homeostasis of biosensor. Both non-hereditary and hereditary disturbances can too much initiate or quiet characteristic enzyme activities. Due to its virtuous sensitivity, easy to operate, high precision and low instrumentation cost it can be used for recognition of various analytes in different fields than the traditional analytical methods. The enzyme based biosensor is most commonly used dominant tool for the determination of various biological importance such as antigens, antibodies, therapeutic drugs and metabolites. In regular enzymebased biosensors, signal amplification is not satisfactory for the ultrasensitive identification of biomolecules and it was enhanced by consolidating enzymatic responses with redox cycling of multi-enzyme tags for every discovery test. This chapter explains the working principles, features, types, sensing methods and applications of enzyme based biosensor in various fields.

Crop improvement represents the genetic alteration of plants to gratify human needs. Crop improvement, the art of engineering plants for the benefit of humankind, is as old as agriculture itself. Even though crop improvement programs focus on the development of novel crop varieties with enhanced quality and tolerance to ecological stresses (both biotic and abiotic) and making crops able to give more yield exhibiting good quality. Still, we cannot rely on the crops due to various reasons, like the irritating nature of onion, low lysine and threonine content in Maize, the presence of toxic Gossypol in cotton, etc. These irritating qualities of the crop must be reduced or removed by genetically modifying the crop plants, and then only it will be accepted for human consumption. Expression of antisense genes and the related genesilencing technique has been exploited as an applied technique in plant biotechnology for creating “metabolic engineered plants” in which the endogenous target gene, which is responsible for the unpleasant character is specifically suppressed. The antisense and its related technology are used for various purposes such as silencing or ablating undesired genes. In the present chapter, the down-regulation of the enzyme using the gene-silencing technique used in various crop varieties are discussed in detail.

A biosensor is an analytical apparatus, which connects a biologically sensitive and selective component and a physiochemical transducer. Biologically sensitive elements include organisms, tissues, cells, etc. and the transducer includes electrochemical, optical, thermal or mechanical signals which are received and converted into a measurable signal. There are different categories of biosensors based on the principle of working. Some of them are electrochemical, amperometric, thermometric, optical, microbial and immunosensors. Biosensors are broadly used in different areas like the food industry, fermentation industry, pharmaceutical industry, etc. The present chapter explains the use of different types of biosensors which are based upon enzyme inhibition, as an investigative and diagnostic tool. Some of the enzyme inhibitors such as pollutants are strongly associated with human as well as environmental health, so these have to be monitored with strong significance. Thus enzyme inhibition based enzyme biosensors will be a precious tool for very fast performing and accurate for the above applications.

Matrix metalloproteinases are proteolytic zinc-dependent enzymes that play a pivotal function in cell migration, proliferation, differentiation, programmed cell death, and other physiological processes. Recent studies demonstrated that the imbalance activation and inhibition of these enzymes resulted in unexpected physiological and pathological processes. Thus, it fueled the interest in matrix metalloproteinase and its inhibitors in medicinal and pharmaceutical chemists. This chapter discusses the therapeutic accomplishments of matrix metalloproteinase inhibitors in arthritis, autoimmune disease, inflammations, cancer, and cardiovascular disease. Further, the chapter discusses clinical trial implications, obstacles, and future research.

A biosensor is an electrical device encompassing biological components, with the intent to detect and measure the concentration of the analyte in a sample. The applications of the biosensor are numerous including, but not limited to food, healthcare and environmental sectors. In particular, biosensors based on enzymatic inhibition are highly sensitive in monitoring the inhibitory analytes affecting the catalytic activity of enzymes. A careful selection of transducer, a biosensor component for transforming the biochemical signal to an electrical signal along with the choice of enzymes is crucial in determining the commercial viability of enzymatic inhibitory biosensor. This chapter highlights the recent studies as well as products available in the market related to biosensors based on enzymatic inhibition. Besides, the economic analysis of existing and futuristic biosensors is also discussed.

Many organisms are used for alcohol production in an industry that includes Saccharomyces cerevisiae, Zymomonas mobilis, and Clostridium spare better microbes with respect to ethanol production and ethanol tolerance, Zymomonas mobilis can use glucose, sucrose, and fructose through Entner-Deodoroff pathway. In bioprocessing product inhibition is undesirable that limits the product's final titer and volumetric productivity more precisely known as product toxicity those utilizing the whole cell as biocatalyst. During the ethanol fermentation the yield of cell mass decreases gradually as the ethanol concentration increases progressively indicating product inhibition. The decrease in cell mass concentration is the accumulation of ethanol in the fermentation broth beyond the limits. This is because the increase in alcohol concentration during fermentation destroys the microorganism lipid bilayer membrane and denatures the enzymatic protein thereby creating instability conditions. The product inhibition is very well studied only in the batch reactor. Conventionally maximum ethanol concentration of 7-8% (v/v) is achieved in the time frame of 50-70 hr with the operating temperature of the 32-34oC and stirring rate of 180rpm during fermentation. To overcome this problem the continuous product removal solves the product inhibition through maintaining the ethanol concentration below the inhibitory limit.

Bioethanol is the most used biofuel worldwide. Its use contributes to the reduction of fossil fuel consumption and environmental pollution. It is mainly produced from sucrose, which is available in alternative media. Yeast, mainly Saccharomyces cerevisiae, are the most employed microorganisms for ethanol production. These strains usually present high productivity, high ethanol tolerance, and the ability to ferment different sugars that are included in the composition of the highly utilized feedstock. Nevertheless, there are some barriers to yeast fermentation to overcome. They are linked to inhibitors of ethanol production, including high temperature, high ethanol concentration, and the ability to ferment pentose sugars. The efficiency and productivity of ethanol can be enhanced by the use of genetically modified yeast strains, including hybrid and recombinant. Other possibilities of limiting bioethanol processing inhibition are metabolic engineering of the medium and yeast cell immobilization. This chapter highlights some aspects that involve fermentation strategies to minimize bioethanol inhibition during its production.

Persistent Organic Pollutants (POPs) are organic compounds of mainly anthropogenic origin posing a huge threat to human health and the ecosystem. Though the production and intended use of major POPs are banned by Stockholm Convention, still some POPs are being used in most developing countries around the globe. Although, environmental levels of some POPs, such as Polychlorinated biphenyls (PCBs) have declined, newly added POPs in the list of conventions, such as Polybrominated Diphenyl Ethers (PBDEs), Perfluorooctanesulfonate (PFOS) have emerged as new challenges. Exposure to POPs has been associated with a wide spectrum of health effects, including developmental, carcinogenic immunologic, reproductive, and neurotoxic effects. It is of major concern that the neurotoxic effects of some POPs have been observed in humans at low environmental concentrations. This chapter focuses on various POPs like PCBs, PBDEs, and PFOS as a representative chemical class of POPs and discusses the possible modes (s) of action for the neurotoxic effects with an emphasis on comparing dose-response and structure-activity relationships (SAR) with other structurally related chemicals. There are sufficient epidemiological and experimental studies carried out in different parts around the globe showing that PBDEs and PFOS exposure is associated with motor and cognitive deficits in humans and animal models. Several potential mechanisms were presumed for PBDEs and PFOs induced neurotoxic effects and alteration in neurotransmitter systems. Among them, the intracellular signaling processes and hormonal imbalance impacting the activity of thyroid hormone were reported as predominant. All these potential mechanisms are discussed in detail in the chapter. In addition to this, SAR will be highlighted for examining the toxicity of other relevant and structurally similar POPs to assess if they have a common mode(s) of action. Potency factors for several other POPs will also be described focusing on their effects on intracellular signaling processes and enzymatic activity and cell signaling pathways. This chapter is a comprehensive review, describes the alteration of enzymatic pathways and their associated toxicity at the biochemical level in different models for environmentally relevant POPs.

Globally millions of women die of cancer, the most common cancer occurrence sites for women being breast, cervical and ovarian. Engineered enzyme inhibitors are a component of the drug regimen that has taken a drive into pharmaceutical international corporations’ product portfolios which is by targeted delivery, moderating disease-free survival and leading to procrastination of death. Since 2002 the enzyme inhibitor anastrozole (Arimidex) is used as the first drug of choice for breast cancer which is available in the commercial market. Currently, there are several other FDA approved enzyme inhibitors like sulfonanilide analogs available in the pharmaceutical shelf decreasing aromatase expression and regulating enzyme activity for the treatment and cure of breast cancer.

Enzyme inhibitor molecules are used for the development of antiviral drugs. Understanding the mechanisms of enzyme inhibitors are needed for the treatment of HIV, Chikungunya, Dengue, Ebola, Influenza, and Nipah viral diseases. Inhibition of viral entry and its replication in the host cell was the most prominent mode of action against these viruses. In this chapter, the detailed list of plant compounds to be used as drugs for the treatment of above viral diseases through targeting of enzymes, reverse transcriptase, and RNA-dependent RNA polymerase is explained. Recent advancements such as emerging technologies, Next Generation Sequencing, and CRISPR used as an effective approach for the diagnosis, treatment, and alleviation of viral disease progression, are explained.

Enzyme inhibitors are widely prescribed drugs for many diseases including neurological disorders and today most of the drugs are enzyme inhibitors and are in the clinical/pre-clinical phase of the drug discovery. For many of the neurological disorders, especially neurodegenerative disorders, only symptomatic therapy is available rather than the therapy based on an understanding of the mechanism of these diseases. In this case, enzyme inhibitors become the solution as they inhibit the action of enzymes whose abnormal activity may be one of the causes of the disease. They also halt the progression of the disease and alleviate the symptoms. This chapter focuses on some of the enzyme inhibitors that have been prescribed as drugs for neurological disorders, their mechanism of action and discuss some inhibitors that are still in their research level of development.