Disruption of the Cell Membrane or Wall

The cell membrane acts as a selective barrier, allowing some solutes to pass through and excluding others. Many com pounds are actively transported through the membrane, becoming concentrated within the cell. The membrane is also the site of enzymes involved in the biosynthesis of components of the cell envelope. Substances that concentrate at the cell surface may alter the physical and chemical properties of the membrane, preventing its normal functions and therefore killing or inhibiting the cell.

The cell wall acts as a corseting structure (best characterized as a fishing net), protecting the cell against osmotic lysis. Thus, agents that destroy the wall (eg, lysozyme, which cleaves the sugar linkages of peptidoglycan) or prevent its normal synthesis (eg, penicillin, which interrupts peptidyl cross-linkages) may bring about lysis of the cell.

Protein Denaturation

Proteins exist in a folded, three-dimensional state determined primarily by intramolecular noncovalent interactions such as ionic, hydrophobic, and hydrogen bonds or covalent disulfide linkages. This state is called the tertiary structure of the protein; it is readily disrupted by a number of physical (eg, heat) or chemical (eg, alcohol) agents, causing the protein to become nonfunctional. The disruption of the tertiary structure of a protein is called protein denaturation.

Disruption of Free Sulfhydryl Groups

Enzymes containing cysteine have side chains terminating in sulfhydryl groups. In addition to these, coenzymes such as coenzyme A and dihydrolipoate contain free sulfhydryl groups. Such enzymes and coenzymes cannot function unless the sulfhydryl groups remain free and reduced. Oxidizing agents thus interfere with metabolism by forming disulfide linkages between neighboring sulfhydryl groups:

Many metals such as mercuric ions likewise interfere by combining with sulfhydryls. There are many sulfhydryl containing enzymes in the cell, so oxidizing agents and heavy metals do widespread damage.

Damage to DNA

 A number of physical and chemical agents act by damaging DNA; these include ionizing radiations, ultraviolet light, and DNA-reactive chemicals. Among the last cate gory are alkylating agents and other compounds that react covalently with purine and pyrimidine bases to form DNA adducts or interstrand cross-links. Radiation can dam age DNA in several ways: Ultraviolet light, for example, induces cross-linking between adjacent pyrimidines on one or the other of the two polynucleotide strands, forming pyrimidine dimers; ionizing radiations produce breaks in single and double strands. Radiation-induced and chemically-induced DNA lesions kill the cell mainly by interfering with DNA replication. See Chapter 7 for a discussion of DNA repair systems.

Chemical Antagonism

The interference by a chemical agent with the normal reaction between a specific enzyme and its substrate is known as chemical antagonism. The antagonist acts by combining with some part of the holoenzyme (the protein apoenzyme, the mineral activator, or the coenzyme), thereby preventing attachment of the normal substrate. (Substrate here is used in the broad sense to include cases in which the inhibitor com bines with the apoenzyme, thereby preventing attachment of the coenzyme.)

An antagonist combines with an enzyme because of its chemical affinity for an essential site on that enzyme. Enzymes perform their catalytic function by virtue of their affinity for their natural substrates; hence any compound structurally resembling a substrate in essential aspects may also have an affinity for the enzyme. If this affinity is great enough, the “analog” will displace the normal substrate and prevent the proper reaction from taking place.

Many holoenzymes include a mineral ion as a bridge either between enzyme and coenzyme or between enzyme and substrate. Chemicals that combine readily with these minerals will again prevent attachment of coenzyme or substrate (eg, carbon monoxide and cyanide combine with the iron atom in heme-containing enzymes and prevent their function in respiration).

Chemical antagonists can be conveniently discussed under two headings: (a) antagonists of energy-yielding processes and (b) antagonists of biosynthetic processes. The former include poisons of respiratory enzymes (carbon monoxide, cyanide) and of oxidative phosphorylation (dinitrophenol); the latter include amino acid and nucleic acid analogs. In some cases, the analog simply prevents incorporation of the normal metabolite (eg, 5-methyltryptophan prevents incorporation of tryptophan into proteins), and in other cases, the analog replaces the normal metabolite in the macromolecule, causing it to be nonfunctional. The incorporation of p-fluorophenylalanine in place of phenylalanine in proteins is an example of the latter type of antagonism.

اخر الاخبار

اخبار العتبة العباسية المقدسة

شعبة الخطابة النسوية تطلق دورة تخصصية لقارئات المنبر الحسيني وخطيباته

المجمع العلمي ينظّم سفرة دينية لطلبة مشاريعه القرآنية في كربلاء

عبر مجلّة (تراث الجنوب) المحكّمة.. قسم شؤون المعارف يوثق إرث مدن جنوب العراق

في ذكرى تأسيسه.. متحف الكفيل يستعرض مسيرته في حفظ التراث الإنساني والإسلامي

المزيد

الآخبار الصحية

فيروس هانتا والسفينة الموبوءة.. تحديث من الصحة العالمية

طبيب يحسم الجدل السجائر الإلكترونية وعلاقتها بالسرطان

فيروس يرعب سفينة.. ماذا نعرف عن "هانتا"؟

السجائر الإلكترونية والإقلاع عن التدخين.. نتائج متباينة تثير الجدل العلمي

المزيد

الآخبار التكنلوجية

أحلامك ليست عشوائية.. إليك ما يفعله دماغك أثناء نومك

روسيا.. العلماء يضاعفون الاستقرار الحراري للألواح الشمسية ثلاث مرات

علماء يكشفون سر سرعة الدلافين في السباحة

سلمي أو دموي.. هكذا تنتقل السلطة في مجتمع الجرذان

المزيد

مواضيع ذات صلة

Availability of Reliable Susceptibility Testing Methods

Predictability of Antimicrobial Susceptibility

Emergence and Dissemination of Antimicrobial Resistance

Microorganism-Mediated Antimicrobial Resistance

Environmentally Mediated Antimicrobial Resistance

Inhibitors of Other Metabolic Processes

Inhibitors of DNA and RNA Synthesis

Common Pathways for Antimicrobial Resistance

Antimicrobial Chemoprophylaxis

Drug–Pathogen Relationships

Measurement of Antimicrobial Activity

Clinical Implications of Drug Resistance