Skip to main content

Renin Angiotensin Mechanism.

Inhibitors of ETC and oxidative phosphorylation / Uncouplers.

 

Definition of Inhibitors of ETC and oxidative phosphorylation.:

  • The compounds which inhibit ETC and hence affect oxidative phosphorylation.

  • These inhibitors bind to the respiratory chain, and not to the enzymes involved in ATP synthesis, which would normally accompany respiration.

  • Their actions may be mediated by 3 positions that are similar to energy transfer sites I, II, and III.

Examples of Inhibitors:

  1. Rotenone

    • Electron transport chain inhibitor that is non-toxic.

    • Obtained from the extracts of roots of tropical plants Derris elliptica. 

    • It binds in Complex I.

    • Mammals cannot be harmed by this substance since it is poorly absorbed. 

    • Fish are affected by their toxicity.

  2. Pieridine A

    • Antibiotics are used to treat infections (safer in Humans).

    • Strains of Streptomyces produce it.

    • It acts similarly to Rotenone.

  3. Barbiturates:

    • Coenzyme Q and NADH dehydrogenase are blocked, one of the reason of respiratory failure in barbiturate poisoning.

  4. Antimycin

    • Streptomyces produces antibiotics called antimycins. Antimycin is an electron transport chain inhibitor.

    • Site II is inhibited and electrons are prevented from flowing between cytochromes b and c1, preventing ATP synthesis coupled with the formation of a proton gradient.

  5. Dimercaprol

    • Similar to antimycins, it acts similarly.

  6. Hydrogen sulfide

    • The disagreeable odor of H2S provides a warning that it is toxic.

    • Oxidase is inhibited by H2S.

  7. Carbon monoxide

    • Oxygen and cytochrome oxidase is blocked.

    • Fer2+ is inhibited as well.

Definition of uncouplers:

  • An uncoupler is a substance that prevents electron transfer during phosphorylation of ADP. 

  • Compounds that uncouple ATP synthesis from electron transport through the cytochrome system are uncoupling agents. 

  • In this case, oxygen is consumed, but phosphorylation of ADP is inhibited, despite electron transport continuing to function.

Examples of Uncouplers:

  1. 2,4-Dinitrophenol

    • Oxidative phosphorylation is a classic uncoupler.

    • The substance transports protons across mitochondrial membranes.

    • This uncoupler prevents mitochondria from forming ATP when electrons are transported from NADH to O2. The protons in the inner mitochondrial membrane are dissipated, resulting in the production of ATP.

    • In metabolic studies, DNA or other uncouplers are extremely useful because of their specific effect on phosphorylation outside the cell.

  2. Dicoumarol (Vitamin K analogue)

    • Inhibits the formation of blood clots.

  3. Calcium

    • Uncoupling can be caused by Ca+2 ions being transported into mitochondria.

    • Oxidative phosphorylation is tightly coupled to mitochondrial Ca+2 transport.

    • Uptake of pi is also involved.

    • Electron transport can occur in mitochondria when calcium is transported there, but energy is required to pump Ca+2 into the mitochondria. ATP cannot be stored as a result.

  4. CCCP (Chloro Carbonyl Cyanide Phenylhydrazone)

    • Uncoupler with the most activity.

    • Protons can cross the inner mitochondrial membrane with the help of these lipid-soluble substances.

  5. Physiological uncouplers

    • Thyroxine hormone is produced in excess

    • Brown adipose tissue contains long-chain FA

    • The unconjugated form of hyperbilirubinemia

  6. Valinomycin

    • It is produced by the streptomyces.

    • There are four types of residues in this repeating macrocyclic molecule (L-lactate, L-Valine, D-hydroxyisovalerate, and D-Valine).

    • Reduces the proton gradient by transporting K+ from cytosol to matrix and H+ from matrix to the cytosol.

Commonly Asked Questions:

  1. Define and explain Inhibitors of ETC and oxidative phosphorylation.

  2. What are Uncouplers? Give some examples.
Labels:

Popular posts from this blog

Heat Exchangers and Heat Interchangers.

  In pharmaceutical industries many types of equipments are used for transfer of heat, they can be classified as follows, Heat Exchangers. Heat Interchangers. Heat Exchangers: These devices are used for transferring heat from a fluid (Hot Gas or Steam) to another fluid (Liquid) through a metal wall. Heat Interchangers: These devices are used for transferring heat from a One liquid to another liquid or one gas to another gas through a metal wall. HEAT EXCHANGERS; The equipment used for heat transferring are known as heat exchangers. Some of the processes that involves heat transfer in pharmaceutical industries are: Preparation of starch paste (in steam jacketed kettle). Crystallization. Evaporation. Distillation.  Classification of heat exchangers On the basis of transfer of heat, heat exchangers are classified as: Direct transfer type:  The hot and cold fluids are separated by a metal wall through which the heat is transferred from hot fluid to cold fluid. E.g. shell and ...
Read more

Glycogenesis.

  Definition: Biosynthesis of Glycogen from Glucose is called Glycogenesis. Glycogen is synthesized  Depending on the demand for glucose and ATP (energy), insulin promotes the glucose conversion into glycogen. Glycogen is the major storage form of carbohydrate in animals similar to starch in plants. It is a homopolymer made up of repeated units of α- D glucose and each molecule is linked to another by 1→4 glycosidic bonds . Once there is a chain consisting of 8 to 10 glycosidic residues in the glycogen fragment, branching begins by 1→6 linkages . Glycogen is stored in liver and skeletal muscles. Location: Cytoplasm of cells in the muscle, liver, and adipose tissue. Steps Involved in Glycogenesis: Glucose is converted into glucose-6-phosphate by the action of glucokinase or hexokinase  with conversion of ATP to ADP. Glucose-6-phosphate is converted into glucose-1-phosphate by the action of phosphoglucomutase. Glucose-1-phosphate is converted into UDP-glucose by the actio...
Read more

Rate of Drying Curve.

  Definition Drying is defined as the removal of liquid from a product usually with application of heat. Rate of Drying Curve. Drying process can be divided into three periods Initial Adjustment Period. Constant drying rate period. First falling drying rate period. Second falling rate period. Initial Adjustment Period (A-B): Also called the “ Heating up” period . In this period the substance gets heat and increases in temperature. Drying has not yet started. Constant drying rate period (B-C): During this period the temperature of the solid and the rate of drying remain constant. The moisture evaporating from the surface is replaced by water diffusing from the interior of the solid at a rate equal t o the rate of evaporation.  The moisture content at the end of constant rate (point C) is referred to as the critical moisture content (CMC).  At CMC, dry spots start appearing and drying rate starts falling . First falling drying rate period (C-D): This period is also called ...
Read more