Metabolic Poisons

Oligomycin

References:

"Metabolic Process." Gene Ontology Consortium. N.p., n.d. Web. 4 June 2016.

http://geneontology.org/page/metabolic-process

"What Are the Different Metabolic Processes." N.p., n.d. Web. 4 June 2016.

http://mwisegeek.org/what-are-the-different-metabolic-processes.htm

"Cyanide Poisoning: Get Facts About Effects and Treatment." EMedicineHealth. N.p., n.d. Web. 5 June 2016.

http://www.emedicinehealth.com/script/main/mobileart-emh.asp?articlekey=58915

"Selected Metabolic Poisons." Metabolic Poisons. N.p., n.d. Web. 5 June 2016.

http://www.ruf.rice.edu/~bioslabs/studies/mitochondria/mitopoisons.html

"Department of Health." The Facts About Cyanides. N.p., n.d. Web. 6 June 2016.

https://www.health.ny.gov/environmental/emergency/chemical_terrorism/cyanide_general.htm

"The Naked Scientists." Cyanide Poisoning. N.p., n.d. Web. 10 June 2016.

http://www.thenakedscientists.com/HTML/articles/article/alexandralindsaycolumn1.htm/

http://www.bmb.leeds.ac.u/illingworth/oxphos/poisons.htm

http://oxfordreference.com/view/1.1093/oi/authority.20110803100152702

http://www.biologyreference.com/ph-po/poisons.html

• Acts by binding ATP synthase to block the proton channel
• Oligomycin inhibits oxidative phosphorylation
• It has no effect on stage 4 respiration and no direct effect on ET or the chemiosmotic gradient .
• It prevents state 3 respiration completely.
• Effects don't show for awhile

Uncoupling Agents

Electron Transport System Inhibitors (ETS Inhibitors)

• The rate of E.T. (electron transport) can not be regulated anymore by an intact chemiosmotic gradient.
• It differs from ETS inhibition since bypassing the block would restore the gradient.
• The electron transport system in uninhibited due to the complete and irreversible dissipation of the chemiosmotic gradient.

Ex. 2,4- Dinitrophenol (DNP)

- DNP binds protons on one side of a membrane, and since it is fat-soluble it drifts to the other side where it loses protons.

- DNP gradually inhibits electron transport itself as it is incorporated into mitochondrial membranes.

-The uncoupling of electron transport from ATP synthesis allows fast oxidation of Krebs substrates, which promotes the mobilization of carbohydrates and fats. -Since the energy is lost as heat, biosynthesis is not enhanced, and weight loss is dramatic.

- It was used as a diet pill in the early 1930s but many patients were killed from it as it's not a good idea to mess with cell metabolism.

Health effects from exposure to DNP

• Acute oral exposure to DNP can result in increased basal metabolic rate, nausea, vomiting, sweating, dizziness, headache, and loss of weight.
• Chronic oral exposure to DNP can lead to the formation of cataracts and skin lesions and has caused effects on the bone marrow, central nervous system, as well as the cardiovascular system.

Environmental Effects

• DNP is considered an important environmental contaminant by the United States Environmental Protection Agency.
• It can enter the air from automobile exhaust, burning of certain industrial substances, and from reaction of nitrogen in air with other atmospheric chemicals.
• DNP forms explosive salts with strong bases and ammonia, and emits toxic fumes of nitrogen dioxide when heated to decomposition.

- Bind to ETS and prevent electrons from being passed from one carrier to the next

-Each inhibitor acts specifically in which each inhibitor binds a particular complex in ETS

-Irreversible inhibition results in a complete stop of respiration via the blocked pathway

-Competitive inhibition allows some consumption of oxygen but it prevents the maintenance of a chemiosmotic gradient, so the addition of ADP has no effect on respiration.

Cyanide:

What happens when cyanide is consumed:

• It is attached to the iron within the fourth complex in the Electron Transport Chain and inhibits the normal activity of the complex system.
• It binds tightly making it unable to transport any electrons to oxygen, blocking the further passage of electrons throughout the chain and stopping ATP production.
• Since no ATP is being produced, the electron transport chain stops working because the protons are not allowed to go back into the matrix of the mitochondria. This causes an enlargement in the concentration of proton buildup.
• The person who consumed the cyanide, would be deprived of chemical energy to perform the many processes that sustain life and the person would die.

Symptoms of Cyanide Poisoning:

The signs and symptoms from high levels of cyanide exposure can begin within seconds to minutes.The intensity of health effects depends on the route as well as duration of exposure, the dose, and the form of cyanide. Some signs and symptoms of cyanide exposures are:

• Weakness and confusion
• Headache
• Nausea
• Difficulty breathing
• Loss of consciousness
• Seizures
• Cardiac arrest

What can you do if you think you may have been exposed to a release of cyanide?

• Move away from the area where you think you were exposed. If the release of cyanide was indoors, go outdoors.
• Quickly remove any clothing that may have cyanide on it. Clothing that is normally removed over the head (t-shirts and sweaters) are to be cut off the body to prevent additional contact with cyanide.
• Place your clothing inside a plastic bag and seal the bag tightly. Store the bagged clothing in a secure location away from people.
• Wash any cyanide from your skin with big amounts of soap and water, and flush your eyes with lots of water.
• If needed, seek medical attention right away.

How is cyanide exposure treated?

Often patients are given oxygen to treat the exposures. Two antidotes; sodium nitrite and sodium thiosulfate, are usually used to end the effects of severe cyanide poisoning. Other drugs may be used in order to control additional health effects of cyanide such as seizures. People who experience serious signs and symptoms will need immediate hospital care (passed out or unconscious). Any delay in treatment could result in death.

Cyanide is a chemical compound that is made of a carbon atom triple- bonded to a nitrogen atom. It is an extremely effective reversible inhibitor of cytochrome oxidase . It is one of the most deadly compounds in a laboratory.

There are several chemical forms of cyanide.

Ex :

Hydrogen cyanide :

-is a pale blue or colorless liquid at room temperature and is a colorless gas at higher temperatures

-has a bitter almond odor.

How people can be exposed to cyanide :

• People may be exposed to low levels of cyanides in their daily lives from foods, smoking and other sources.
• Eating or drinking cyanide-containing foods may cause health effects.
• Breathing cyanide gas, especially in a poorly ventilated space, has the greatest potential for harm.
• Lethal exposures to cyanides result only from accidents or intentional acts.

Metabolic Poisons

A metabolic poison is a compound that poisons a metabolic process. It directly interferes with a biochemical pathway that's involved in energy utilization or production.

The three main types of metabolic poisons:

ETS inhibitors: Bind somewhere on the electron transport chain, preventing electrons from being passed from one carrier to the next.

Uncoupling agents: The rate of electron transport can no longer be regulated by an intact chemiosmotic gradient.

Oligomycin: Bind to ATP synthase and block the proton channel, inhibit oxidative phosphorylation.

Poisons

Poison is a substance that is dangerous to living organisms.

Almost any substance can be poisonous at high enough concentrations, especially many substances that are used for medicine.

Poisons disrupt metabolic processes or destroy tissue through chemical reactions with cells

Three Major Routes of Exposure For Poisons:

Metabolic Processes

Metabolic processes are sequences of biochemical reactions that take place within living cells to maintain life.

They can be divided into two main types:

- Catabolic process: involves the breakdown of complex molecules from food into smaller units that can be used as building blocks for new molecules and also to provide energy.

Example: Digestion

- Anabolic process: uses energy to build new chemicals that become components of cells.

Example: The synthesis of glucose from H2O and CO2 through photosynthesis

Metabolism

In order for all life processes to occur, thousands of chemical reactions take place within our cells.

In some chemical reaction taking place, large molecules (polymers like DNA) are built from small molecules (monomers like nucleotides). In other chemical reactions, polymers like amylose undergo hydrolysis into monomers like glucose.

The sum of these processes taking place within an organism is called its metabolism.

The process of metabolism includes both biosynthetic and catabollic processes.

Both of these processes can be broken down into two subclasses: organismal and cellular metabolism.

Metabolic Poisons

How Poisons Affect Metabolic Processes

By: Rebecca, Lauren S., Alysha & Sophia