the study of alcohol ethanol metabolism

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Alcohol has been part of human civilization for thousands of years. Actually, one of the oldest recipes recorded, is for a beverage similar to beer. Alcohols are identified by containing a C-O-H unit in their moleular structure. This is called the alcohol functional group. Most of the common alcohols are colorless liquids at room temperature. Methyl alcohol, ethyl alcohol, and isopropyl alcohol are free-flowing liquids with fruity odors. The higher carbon containing alcohols- 4 to 10 carbon atoms-are somewhat viscous, or oily, and they have heavier fruity odors. Some of the highly branched alcohols and many alcohols containing more than 12 carbon atoms are solids at room temperature. (Encyclopedia Britannica)

The hydroxyl group(-OH) generally makes the alcohol molecule polar. This is because the oxygen atom is more electronegative which results in it pulling the electrons away from the nearby carbon atoms. These hydroxyl groups can form hydrogen bonds to one another and to other compounds such as water. The ability for these compounds to be miscible in water is important when it comes to the ingestion and effects of it.

The different side chains on alcohol functional groups cause the resulting chemical to have extremely different effects when ingested. Methanol (CH3OH), also known as wood alcohol, is typically made from natural gas (Baird 214-229). Methanol itself is relatively nontoxic. However, during metabolism, the enzyme alcohol dehydrogenase converts it into formaldehyde, which is extremely toxic to the liver and kidneys (Goldfrank). Formaldehyde gets reduced to formic acid, which causes proteins to precipitate and cause immediate cell death. Ethanol (CH3CH2OH) on the other hand, is less toxic for humans to ingest. The intermediate metabolites are less harmful than that of methanol. Ethanol is the form of alcohol that most people think of when they hear the word. It is the type that is present in alcoholic beverages. The words ethanol and alcohol are used interchangeably.

Ethanol is produced by fermentation and distillation. Fermentation is defined as the enzymatically controlled anaerobic breakdown of an energy-rich compound. Simple sugars are the raw material and zymase, an enzyme from yeast, converts these simple sugars into ethanol and carbon dioxide. The reaction proceeds as follows: C6H12O6 à 2 CH3CH2OH + 2CO2. The ethanol produced by fermentation ranges in concentrations from a few percent up to 14 percent. Above 14 percent, ethanol destroys the enzyme zymase, and fermentation stops. Ethanol is normally concentrated by distillation; this is the process of purifying a liquid by successive evaporation and condensation. The resulting content is about 95 percent alcohol. A dehydrating agent is then added to remove the remaining water, which produces 100 percent pure ethanol. (Shakhashiri)

Once ethanol is ingested, it immediately begins to produce effects throughout the entire body. After swallowed, alcohol begins to be absorbed into the bloodstream through the lining of the digestive tract. The digestive tract, for purposes of absorbing alcohol, consists of the stomach and intestines. About 20 percent of the alcohol consumed is absorbed within the stomach, and the remaining 80 percent is absorbed within the small intestines (Baird 214-229). Since alcohol is water soluble, it dissolves into the water portion of blood plasma. Then the alcohol gets carried throughout the entire body and is absorbed into the body tissues of major organs to produce its effects (Intoximeters Inc.). Speifically the liver, brain, and kidneys.

The effects of alcohol on different tissues depend on the concentration of it in the blood over a period of time. Blood alcohol concentration (BAC) is determined by how quickly alcohol is absorbed, transported, metabolized, and expelled. This number is presented as a percentage and is used as a measurement of intoxication. Some factors that affect BAC are the amount and the rate of alcohol ingested, body weight, presence of food in the stomach, type of alcohol and the type of mixer used. When one drinks alcohol quickly, the BAC will peak quickly and it will take the liver longer to metabolize the alcohol. This keeps the alcohol circulating in the blood causing it to affect vital organs for a greater period of time. Heavier individuals have more blood and water in their bodies, which dilute the alcohol, lowering their BAC. When there is food in the stomach, alcohol is absorbed more slowly into the bloodstream. Since it is absorbed slower, the liver will be able to metabolize the alcohol with out becoming 'over loaded'. The BAC rises more rapidly in those who drink on an empty stomach, because there is no food to slow the speed the alcohol is absorbed into the blood. The stronger a drink is, for example vodka compared with wine, the quicker it is metabolized. Also, water and fruit juices mixed with alcohol, slow the absorption process and carbonated beverages speed it up. Carbon dioxide speeds the alcohol through the stomach and intestine into the bloodstream, creating a rapid rise in BAC. (Blood Alcohol Concentration)

Capillaries in the lining of the digestive tract absorb the alcohol and transport it to the body's venous system. Once the alcohol reaches the small intestines, it is absorbed into the portal vein. The portal vein is the main vein that leads to the liver. The liver is the main organ that is responsible for metabolizing ingested alcohol.

Ethyl alcohol is metabolized through both oxidative and non-oxidative pathways. Alcohol dehydrogenase, aldehyde dehydrogenase, cytochrome P450 2E1 and catalase, all contribute to the oxidative metabolism of ethanol. These enzymes aren't all activated at the same moment. Alcohol dehydrogenase (ADH) is the first enzyme to be activated under normal conditions; it converts the alcohol into an aldehyde, which then is converted to acetate by aldehyde dehydrogenase (ALDH). Cytochrome P450 2E1 is only activated when an individual has consumed very large amounts of alcohol.

ADH is present in the fluid portion of cells. When ethanol is absorbed into the liver cells, it is metabolized with the alcohol dehydrogenase enzyme. Acetaldehyde, which is an enormously reactive and toxic byproduct, is produced. When high levels of acetaldehyde are present in the blood, an individual will experience facial flushing, undergo light-headedness, feel heart palpitations, become nauseated and general "hangover" symptoms occur (Baird 214-229). This oxidation process of ADH utilizes an intermediate carrier of electrons, nicotinamide adenine dinucleotide (NAD+), which is reduced by two electrons to form NADH. This process leaves the cells in the liver predominantly exposed to damage from the byproducts of ethanol metabolism, such as free radicals and acetaldehyde. (Zakhari 246-247) ALDH is then activated when in the presence of acetaldehyde. This enzyme is responsible for the oxidation of acetaldehyde into acetate. Acetate is easily converted to carbon dioxide by the body's muscles and heart.

The cytochrome P450 2E1 enzyme is present in the endoplasmic reticulum of cells. It belongs to the super family of proteins containing a heme cofactor and are therefore called hemoproteins. This oxidative process by cytochrome P450 is induced by chronic alcohol consumption. The pathway produces reactive oxygen species (ROS) also known as free radicals. A free radical is any chemical species that contains one or more unpaired electrons. The presence of an unpaired electron often causes the free radical to be highly reactive because the free radical acts as an electron acceptor and essentially steals electrons from other molecules. (Ciccone) To prevent the damage these highly reactive compounds can cause, the body has evolved compounds known as antioxidants. These interact with ROS and convert them into harmless molecules.

Oxidative and non-oxidative pathways of ethanol metabolism are interrelated. Inhibition of the oxidative pathways results in an increase in the non-oxidative pathways. The non-oxidative metabolism of ethanol is minimal, but it has physiological relevance. One of the non-oxidative pathways leads to the formation of molecules called fatty acid ethyl esters (FAEEs) from the reaction of alcohol with fatty acids. They are found to be present in patients when they have impaired liver function. The second non-oxidative pathway requires the enzyme phospholipase D (PLD), which breaks down phospholipids to generate phosphatidic acid.

The products of oxidative metabolism of alcohol are very damaging to the liver and can produce detrimental effects. Acetaldehyde is rapidly metabolized to acetate, mainly by aldehyde dehydrogenase (ALDH) in the cells mitochondria. When the rate of drinking is substantially more than the metabolism rate, not all of the aetaldehyde can be converted into acetate. The remianing acetaldehyde has the capacity to bind to proteins which allows for the formation of adducts. Acetaldehyde reacts with a variety of proteins to form both stable and unstable adducts. Adducts are the covalent binding product of a carcinogen, or its metabolite, to a protein. Unstable adducts are easily reversible. On the other hand, stable adducts are irreversible products that are characterized by their resistance to various treatments. Furthermore, it is likely that stable adducts are represented by multiple products whose structures may vary, depending upon the particular target protein. (Tuma 271-276) Adducts in the brain affect the signaling of the neurotransmitter dopamine and in the liver it impairs protein secretion. These contribute to alcohol dependance and enlargment of the liver, respectively.

Acetate, which is produced from the metabolism of acetaldhyde by aldyhyde dehydroganase, is oxidized to carbon dioxide. Most of the acetate escapes into the blood and is metabolized to carbon dioxide by the heart, skeletal muscles and brain.However when there is an acetate 'back-up' in the blood, it increases the blood flow into the liver and depresses the central nervous system and affects various metabolic processes. (Zakhari 248)

The liver is an organ that takes the most abuse from alcohol consumption and is probably the most commonly thought of when discussing the harming effects of alcohol on your body. Also called steatosis, fatty liver is the collection of excessive amounts of triglycerides and other fats inside liver cells. The liver is responsible for converting fats to the type that can be stored and used by the body. Over consumption of alcohol changes the way that the liver breaks down and stores fats. Fatty liver is usually reversible if recognized and treated quickly enough. There may be some long-term tendency toward other types of liver problems depending on how long and how severe the fatty liver condition was. (Medical Dictionary) Alcoholic Hepatitis is the inflammation of the liver caused by alcohol. It is known that when the liver breaks down alcohol, some toxic substances are produced. These substances irritate and inflame the liver, which destroys liver cells. Damage from alcoholic hepatitis often can be reversed in people who stop drinking. (Rennie) Cirrhosis of the liver is the most serious form of liver disease and a cause of many deaths and serious illnesses. Cirrhosis occurs when the cells of the liver are damaged and can't repair themselves. As live cells die, scar tissue forms. When this scar tissue builds up, blood can't flow through the liver properly. The primary job of the liver is to filter and clean the blood supply and when this tissue is scarred, it keeps blood from flowing normally causing a build up of toxins and wastes in the body. (Rennie) When this occurs the body completely shuts down, resulting in death.

Since alcohol is water soluble it is able to cross the blood brain barrier. The brain is the control center of the body; it controls all the systems in your body including your muscular system, your respiratory system and your digestive system. Alcohol contracts brain tissue and depresses the central nervous system. Also, alcohol destroys brain cells and unlike many other types of cells in the body, brain cells do not regenerate. When alcohol reaches the brain, it interferes with communication between nerve cells, by interacting with the receptors on cells. The alcohol suppresses excitatory nerve pathway activity and increases inhibitory nerve pathway activity. Among other actions, alcohol enhances the effects of the inhibitory neurotransmitter GABA and weakens the excitatory neurotransmitter glutamine. Enhancing the effects of these neurotransmitters results in the central nervous system 'slowing down'.

In the brain, the cerebral cortex consists of four lobes: the frontal, parietal, occipital and temporal. The frontal lobe is involved with decision-making, problem solving and planning. When this area of the brain is inhibited, loss of reason and inhibitions occur. This results in the careless, reckless behavior that intoxicated people exhibit. The parietal lobe is involved in the reception and processing of sensory information from the body. This results in the decreased pain sensation that develops when drinking. Also the loss of fine motor skills occurs, in addition to slower reaction time and shaking. The occipital lobe is involved with vision and when inhibited it is responsible for blurred vision and poor distance judgment. The temporal lobe is involved with memory, emotion, hearing, and language. This results in the slurred speech that is a defining characteristic of an intoxicated person, as well as impaired hearing. (Chew) These effects have occurred because ethanol has replaced some of the water around the neurons, which interferes with signaling in the brain. (Baird 223)

The kidneys are a pair of vital organs used to filter waste and excess water from the body. They also release hormones that help regulate blood pressure and keep bones healthy and strong. Kidneys are important organs, but they are also delicate, and damage is irreversible. Individuals who drink often are likely to develop high blood pressure. (Curtis) This causes the blood vessels in the kidneys to become damaged. When these vessels are damaged the kidneys cannot filter the blood appropriately and it results in a build up of unwanted molecules in the kidneys, cause them to die.

To summarize the main concepts, once ethanol is ingested and absorbed through the lining of the digestive system, into the blood stream. It then travels through the portal vein to the liver where the majority of it will get metabolized. In the liver there are two different but interrelated pathways of metabolism that the ethanol can take, the oxidative and the non-oxidative pathway. The most common and most likely to be used is the oxidative pathways. Of which include alcohol dehydrogenase, aldehyde dehydrogenase and cytochrome P450 2E1. Alcohol and aldehyde dehydrogenase work together and cytochrome P450 only becomes activated under intense ethanol intake. The liver metabolizes ethanol into certain byproducts than can be harmful if there are too many in the body. These byproducts, known as acetaldehyde, are what cause the general 'hangover' symptoms. Alcohol not only affects the liver, but also the brain and kidneys. The affect it has on the brain is instantly noticeable. Including slurred speech, unsteady gait and reaction time is noticeably increased. In the kidneys, it may damage the blood vessels and affect the way kidneys filter the blood and this could result in irreversible kidney damage. The body is a remarkable machine and is truly astonishing when it comes to the survival and maintenance of its parts.