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What makes alcohol harmful to mammals?

What makes alcohol harmful to mammals?


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During the alcohol metabolic pathway, harmful by-products are made like acetaldehyde, hydroxyethyl, superox-ide anions, and hydroxyl radicals. How do these toxic compounds harm our tissues? Many of these intermediates are the compounds that are responsible for hangovers, but are they also the molecular cause of liver damage?


Superoxide radicals , basically damage the lipid bilayers. affecting the efficient gradient. for example H+ ion gradient across lipid bilayer in ETC is very important. this gradient is affected if superoxide radicals are present.


What makes alcohol harmful to mammals? - Biology

Number 63 October 2004

ALCOHOL’S DAMAGING EFFECTS ON THE BRAIN

  • how much and how often a person drinks
  • the age at which he or she first began drinking, and how long he or she has been drinking
  • the person’s age, level of education, gender, genetic background, and family history of alcoholism
  • whether he or she is at risk as a result of prenatal alcohol exposure and
  • his or her general health status.

BLACKOUTS AND MEMORY LAPSES

Alcohol can produce detectable impairments in memory after only a few drinks and, as the amount of alcohol increases, so does the degree of impairment. Large quantities of alcohol, especially when consumed quickly and on an empty stomach, can produce a blackout, or an interval of time for which the intoxicated person cannot recall key details of events, or even entire events.

Blackouts are much more common among social drinkers than previously assumed and should be viewed as a potential consequence of acute intoxication regardless of age or whether the drinker is clinically dependent on alcohol (2). White and colleagues (3) surveyed 772 college undergraduates about their experiences with blackouts and asked, “Have you ever awoken after a night of drinking not able to remember things that you did or places that you went?” Of the students who had ever consumed alcohol, 51 percent reported blacking out at some point in their lives, and 40 percent reported experiencing a blackout in the year before the survey. Of those who reported drinking in the 2 weeks before the survey, 9.4 percent said they blacked out during that time. The students reported learning later that they had participated in a wide range of potentially dangerous events they could not remember, including vandalism, unprotected sex, and driving.

Binge Drinking and Blackouts

&bull Drinkers who experience blackouts typically drink too much and too quickly, which causes their blood alcohol levels to rise very rapidly. College students may be at particular risk for experiencing a blackout, as an alarming number of college students engage in binge drinking. Binge drinking, for a typical adult, is defined as consuming five or more drinks in about 2 hours for men, or four or more drinks for women.

Equal numbers of men and women reported experiencing blackouts, despite the fact that the men drank significantly more often and more heavily than the women. This outcome suggests that regardless of the amount of alcohol consumption, females—a group infrequently studied in the literature on blackouts—are at greater risk than males for experiencing blackouts. A woman’s tendency to black out more easily probably results from differences in how men and women metabolize alcohol. Females also may be more susceptible than males to milder forms of alcohol–induced memory impairments, even when men and women consume comparable amounts of alcohol (4).

ARE WOMEN MORE VULNERABLE TO ALCOHOL’S EFFECTS ON THE BRAIN?

Women are more vulnerable than men to many of the medical consequences of alcohol use. For example, alcoholic women develop cirrhosis (5), alcohol–induced damage of the heart muscle (i.e., cardiomyopathy) (6), and nerve damage (i.e., peripheral neuropathy) (7) after fewer years of heavy drinking than do alcoholic men. Studies comparing men and women’s sensitivity to alcohol–induced brain damage, however, have not been as conclusive.

Using imaging with computerized tomography, two studies (8,9) compared brain shrinkage, a common indicator of brain damage, in alcoholic men and women and reported that male and female alcoholics both showed significantly greater brain shrinkage than control subjects. Studies also showed that both men and women have similar learning and memory problems as a result of heavy drinking (10). The difference is that alcoholic women reported that they had been drinking excessively for only about half as long as the alcoholic men in these studies. This indicates that women’s brains, like their other organs, are more vulnerable to alcohol–induced damage than men’s (11).

Yet other studies have not shown such definitive findings. In fact, two reports appearing side by side in the American Journal of Psychiatry contradicted each other on the question of gender–related vulnerability to brain shrinkage in alcoholism (12,13). Clearly, more research is needed on this topic, especially because alcoholic women have received less research attention than alcoholic men despite good evidence that women may be particularly vulnerable to alcohol’s effects on many key organ systems.

BRAIN DAMAGE FROM OTHER CAUSES

People who have been drinking large amounts of alcohol for long periods of time run the risk of developing serious and persistent changes in the brain. Damage may be a result of the direct effects of alcohol on the brain or may result indirectly, from a poor general health status or from severe liver disease.

For example, thiamine deficiency is a common occurrence in people with alcoholism and results from poor overall nutrition. Thiamine, also known as vitamin B1, is an essential nutrient required by all tissues, including the brain. Thiamine is found in foods such as meat and poultry whole grain cereals nuts and dried beans, peas, and soybeans. Many foods in the United States commonly are fortified with thiamine, including breads and cereals. As a result, most people consume sufficient amounts of thiamine in their diets. The typical intake for most Americans is 2 mg/day the Recommended Daily Allowance is 1.2 mg/day for men and 1.1 mg/day for women (14).

Wernicke–Korsakoff Syndrome

Up to 80 percent of alcoholics, however, have a deficiency in thiamine (15), and some of these people will go on to develop serious brain disorders such as Wernicke–Korsakoff syndrome (WKS) (16). WKS is a disease that consists of two separate syndromes, a short–lived and severe condition called Wernicke’s encephalopathy and a long–lasting and debilitating condition known as Korsakoff’s psychosis.

The symptoms of Wernicke’s encephalopathy include mental confusion, paralysis of the nerves that move the eyes (i.e., oculomotor disturbances), and difficulty with muscle coordination. For example, patients with Wernicke’s encephalopathy may be too confused to find their way out of a room or may not even be able to walk. Many Wernicke’s encephalopathy patients, however, do not exhibit all three of these signs and symptoms, and clinicians working with alcoholics must be aware that this disorder may be present even if the patient shows only one or two of them. In fact, studies performed after death indicate that many cases of thiamine deficiency–related encephalopathy may not be diagnosed in life because not all the “classic” signs and symptoms were present or recognized.

Human Brain

Schematic drawing of the human brain, showing regions vulnerable to alcoholism-related abnormalities.

Approximately 80 to 90 percent of alcoholics with Wernicke’s encephalopathy also develop Korsakoff’s psychosis, a chronic and debilitating syndrome characterized by persistent learning and memory problems. Patients with Korsakoff’s psychosis are forgetful and quickly frustrated and have difficulty with walking and coordination (17). Although these patients have problems remembering old information (i.e., retrograde amnesia), it is their difficulty in “laying down” new information (i.e., anterograde amnesia) that is the most striking. For example, these patients can discuss in detail an event in their lives, but an hour later might not remember ever having the conversation.

Treatment

The cerebellum, an area of the brain responsible for coordinating movement and perhaps even some forms of learning, appears to be particularly sensitive to the effects of thiamine deficiency and is the region most frequently damaged in association with chronic alcohol consumption. Administering thiamine helps to improve brain function, especially in patients in the early stages of WKS. When damage to the brain is more severe, the course of care shifts from treatment to providing support to the patient and his or her family (18). Custodial care may be necessary for the 25 percent of patients who have permanent brain damage and significant loss of cognitive skills (19).

Scientists believe that a genetic variation could be one explanation for why only some alcoholics with thiamine deficiency go on to develop severe conditions such as WKS, but additional studies are necessary to clarify how genetic variants might cause some people to be more vulnerable to WKS than others.

LIVER DISEASE

Most people realize that heavy, long–term drinking can damage the liver, the organ chiefly responsible for breaking down alcohol into harmless byproducts and clearing it from the body. But people may not be aware that prolonged liver dysfunction, such as liver cirrhosis resulting from excessive alcohol consumption, can harm the brain, leading to a serious and potentially fatal brain disorder known as hepatic encephalopathy (20).

Hepatic encephalopathy can cause changes in sleep patterns, mood, and personality psychiatric conditions such as anxiety and depression severe cognitive effects such as shortened attention span and problems with coordination such as a flapping or shaking of the hands (called asterixis). In the most serious cases, patients may slip into a coma (i.e., hepatic coma), which can be fatal.

New imaging techniques have enabled researchers to study specific brain regions in patients with alcoholic liver disease, giving them a better understanding of how hepatic encephalopathy develops. These studies have confirmed that at least two toxic substances, ammonia and manganese, have a role in the development of hepatic encephalopathy. Alcohol–damaged liver cells allow excess amounts of these harmful byproducts to enter the brain, thus harming brain cells.

Treatment

  • Treatment that lowers blood ammonia concentrations, such as administering L–ornithine L–aspartate.

  • Techniques such as liver–assist devices, or “artificial livers,” that clear the patients’ blood of harmful toxins. In initial studies, patients using these devices showed lower amounts of ammonia circulating in their blood, and their encephalopathy became less severe (21).

  • Liver transplantation, an approach that is widely used in alcoholic cirrhotic patients with severe (i.e., end–stage) chronic liver failure. In general, implantation of a new liver results in significant improvements in cognitive function in these patients (22) and lowers their levels of ammonia and manganese (23).

ALCOHOL AND THE DEVELOPING BRAIN

Drinking during pregnancy can lead to a range of physical, learning, and behavioral effects in the developing brain, the most serious of which is a collection of symptoms known as fetal alcohol syndrome (FAS). Children with FAS may have distinct facial features (see illustration). FAS infants also are markedly smaller than average. Their brains may have less volume (i.e., microencephaly). And they may have fewer numbers of brain cells (i.e., neurons) or fewer neurons that are able to function correctly, leading to long–term problems in learning and behavior.

Fetal Alcohol Syndrome

Children with fetal alcohol syndrome (FAS) may have distinct facial features.

Treatment

Scientists are investigating the use of complex motor training and medications to prevent or reverse the alcohol–related brain damage found in people prenatally exposed to alcohol (24). In a study using rats, Klintsova and colleagues (25) used an obstacle course to teach complex motor skills, and this skills training led to a re–organization in the adult rats’ brains (i.e., cerebellum), enabling them to overcome the effects of the prenatal alcohol exposure. These findings have important therapeutic implications, suggesting that complex rehabilitative motor training can improve motor performance of children, or even adults, with FAS.

Scientists also are looking at the possibility of developing medications that can help alleviate or prevent brain damage, such as that associated with FAS. Studies using animals have yielded encouraging results for treatments using antioxidant therapy and vitamin E. Other preventive therapies showing promise in animal studies include 1–octanol, which ironically is an alcohol itself. Treatment with l–octanol significantly reduced the severity of alcohol’s effects on developing mouse embryos (26). Two molecules associated with normal development (i.e., NAP and SAL) have been found to protect nerve cells against a variety of toxins in much the same way that octanol does (27). And a compound (MK�) that blocks a key brain chemical associated with alcohol withdrawal (i.e., glutamate) also is being studied. MK� reversed a specific learning impairment that resulted from early postnatal alcohol exposure (28).

Though these compounds were effective in animals, the positive results cited here may or may not translate to humans. Not drinking during pregnancy is the best form of prevention FAS remains the leading preventable birth defect in the United States today.

GROWING NEW BRAIN CELLS

For decades scientists believed that the number of nerve cells in the adult brain was fixed early in life. If brain damage occurred, then, the best way to treat it was by strengthening the existing neurons, as new ones could not be added. In the 1960s, however, researchers found that new neurons are indeed generated in adulthood—a process called neurogenesis (29). These new cells originate from stem cells, which are cells that can divide indefinitely, renew themselves, and give rise to a variety of cell types. The discovery of brain stem cells and adult neurogenesis provides a new way of approaching the problem of alcohol–related changes in the brain and may lead to a clearer understanding of how best to treat and cure alcoholism (30).

For example, studies with animals show that high doses of alcohol lead to a disruption in the growth of new brain cells scientists believe it may be this lack of new growth that results in the long–term deficits found in key areas of the brain (such as hippocampal structure and function) (31,32). Understanding how alcohol interacts with brain stem cells and what happens to these cells in alcoholics is the first step in establishing whether the use of stem cell therapies is an option for treatment (33).


Why Do Women Face Higher Risks?

Studies show that women start to have alcohol-related problems sooner and at lower drinking levels than men and for multiple reasons. 3 On average, women weigh less than men. Also, alcohol resides predominantly in body water, and pound for pound, women have less water in their bodies than men. This means that after a woman and a man of the same weight drink the same amount of alcohol, the woman’s blood alcohol concentration (BAC, the amount of alcohol in the blood) will tend to be higher, putting her at greater risk for harm. Other biological differences may contribute as well.


Denatured Alcohol Chemical Composition

There are hundreds of ways ethanol is denatured. Denatured alcohol that is intended for use as a fuel or solvent typically contains 5% or more methanol. Methanol is flammable and has a boiling point close to that of ethanol. Methanol is absorbed through the skin and is highly toxic, so you really shouldn't use denatured alcohol for making perfume or bath products. There are types of denatured alcohol that are suitable for healthcare products. Specially denatured alcohol (SDA) contains ethanol and another chemical that isn't harmful for use in cosmetics or pharmaceuticals. SDAs often list the denaturant, to aid in guiding proper use.


Your Complete Guide to the Science of Hangovers

New Year's Eve is around the corner. For many of us, that means staying out late, dancing and drinking.

Thus, for some of us, the night of carousing also means a morning of hangovers.

Just in the nick of time, here's our complete guide to the science of hangovers—what we know, what we don't know, and how you can use this information to minimize your suffering.

Why Do Hangovers Happen?

Given that they're such a widespread health phenomenon, it's perhaps a bit surprising that scientists still don't fully understand the causes of a hangover. (They do, however, have a scientific name for them: veisalgia.) It's far from clear why, after all traces of alcohol have been fully expelled from your body, you can still experience a load of awful symptoms, including headache, dizziness, fatigue, nausea, stomach problems, drowsiness, sweating, excessive thirst and cognitive fuzziness.

The simplest and most familiar explanation is that drinking alcohol causes dehydration, both because it acts as a diuretic, increasing urine production, and because people who are drinking heavily for multiple hours probably aren't drinking much water during that time period. But studies examining the link between dehydration and hangovers have turned up some surprising data. One, for instance, found no correlation between high levels of the hormones associated with dehydration and the severity of a hangover. It's most likely that dehydration accounts for some of the symptoms of a hangover (dizziness, lightheadedness and thirst) but that there are other factors at work as well.

Most scientists believe that a hangover is driven by alcohol interfering with your body's natural balance of chemicals in a more complex way. One hypothesis is that in order to process alcohol, your body must convert the enzyme NAD+ into an alternate form, NADH. With an excess buildup of NADH and insufficient quantities of NAD+, the thinking goes, your cells are no longer capable of efficiently performing a number of metabolic activities—everything from absorbing glucose from the blood to regulating electrolyte levels. But this hypothesis, too, has been contradicted by data: In studies, people with severe hangovers weren't found to have lower levels of electrolytes or glucose in their blood.

The most compelling theory, at the moment, is that hangovers result from a buildup of acetaldehyde, a toxic compound, in the body. As the body processes alcohol, acetaldehyde is the very first byproduct, and it's estimated to be between 10 and 30 times as toxic as alcohol itself. In controlled studies, it's been found to cause symptoms such as sweating, skin flushing, nausea and vomiting.

Hangovers could also be driven by the way alcohol messes with your immune system. Studies have found strong correlations between high levels of cytokines—molecules that the immune system uses for signaling—and hangover symptoms. Normally, the body might use cytokines to trigger a fever of inflammatory response to battle an infection, but it seems that excessive alcohol consumption can also provoke cytokine release, leading to symptoms like muscle aches, fatigue, headache or nausea, as well as cognitive effects like memory loss or irritation.

Why Do Some People Get Hangovers More Easily?

Life, alas, isn't fair. Some people are extremely prone to hangovers, and some can drink with impunity.

It seems that genetics are partly to blame. Some people (disproportionately those of East Asian descent) have a mutation in their gene for the enzyme alcohol dehydrogenase that makes it much more effective in converting alcohol into the toxic acetaldehyde. Unfortunately, a significant part of this group also has a mutation in the gene for the enzyme that performs the next metabolic step, leading to a much slower conversion of acetaldehyde into acetic acid. As a result, excess buildup of acetaldehyde can happen quite rapidly. This is known to cause an immediate alcohol flush reaction (colloquially known as "Asian glow"), but might also play a role in hangovers the day after drinking.

There are other factors that affect who experiences hangovers most readily. After having the same number of drinks, women are more likely to experience hangovers than men, though this simply seems to be a result of the fact that women generally have a lower body weight as well: If you control for body weight and compare a man and woman with the same blood alcohol content, their chances of a hangover are similar.

There's conflicting evidence over whether hangovers become more frequent with age. Some studies have suggested [PDF] that adolescents are less likely to experience hangovers, but a recent large-scale survey showed the opposite—that, even controlling for total alcohol consumption, drinkers over the age of 40 experienced fewer and less severe symptoms. The authors noted that it's possible, though, that they consume the same amount of alcohol but with less intensity, spreading their drinks out instead of binging.

Why Do Some Drinks Cause Hangovers More Easily Than Others?

Because the ultimate cause of a hangover is, after all, alcohol, drinks that pack more alcohol into a smaller volume are naturally more likely to give you a hangover. Shots of liquor, in other words, are more dangerous than mixed drinks, beer or wine.

(Image via Verster et al.)

Beyond that, though, some drinks happen to have higher levels of congeners—traces chemicals produced during fermentation—that contribute to hangovers. Studies have shown that high-congener, darker-colored liquors like bourbon and whiskey lead to more severe hangovers than lighter-colored or clear liquors like vodka, which has none. A Dutch study systematically looked at the congener content and hangover risk of a variety of types of alcohol, producing the ranking above. One particular congener called methanol—found in highest levels in whiskey and red wine—has received a large amount of the blame, due to studies showing that it can linger in the body after all alcohol has been eliminated, perhaps accounting for the enduring effects of a hangover.

This, incidentally, could explain widely-held belief that mixing different sorts of liquor can cause a hangover—a greater variety of congeners could well lead to a wider variety of effects. It can't, however, explain any beliefs about the order of these drinks—despite the age-old adage "liquor-then-beer-you're-in-the-clear, beer-then-liquor-you've-never-been-sicker."

How Can You Prevent Hangovers?

The most effective solution is also the most obvious: Don't drink alcohol. Or, at the very least, don't drink to excess.

If you're set on drinking a fair amount, though, there are certain things you can do to minimize your change of a hangover and the severity of its symptoms, and they're all pretty intuitive. Don't drink quickly, on an empty stomach drink slowly, either on a full stomach or while eating. Food doesn't literally absorb the alcohol, but having a full digestive tract slows down the rate at which your body absorbs the drug. Additionally, even though dehydration is only partly to blame, it still plays a role, so staying hydrated while drinking alcohol can help.

How Can You Quickly Cure a Hangover?

Eggs Benedict: not a real hangover cure. (Photo via Wikimedia Commons/Amadscientist)

Is there a super food/drink/ritual that can magically removes the after-effects of a night spent binge drinking? Well, according to various local legends, you can cure a hangover by eating shrimp (Mexico), pickled herring (Germany), pickled plums (Japan) or drinking coffee (U.S.), strong green tea (China) or tripe soup (Romania). A number of popular foods and beverages—like the Bloody Mary, Eggs Benedict and even Coca-Cola—were even developed specifically to "cure" hangovers.

Unfortunately, there's no evidence that any of these homespun remedies do anything to help. There's also no evidence that the so-called "hair of the dog" technique (that is, drinking the morning after) has any effectiveness whatsoever. It might temporarily dull your senses, making you less aware of the hangover symptoms, but it does nothing to resolve the underlying physiological problems—and, of course, it can just lead to another hangover.

Other drinkers vouch for a variety of seemingly scientific cures—Vitamin B or caffeine, for instance—but studies have also failed to show that these provide any relief either.

So what can you actually do? You can lessen some of the symptoms with well-known over-the-counter drugs: non-steroidal anti-inflammatories, such as aspirin or ibuprofen (Advil), can treat headaches and other pain, while you can take stomach relief medicines (say, Tums or Pepto-Bismol) to reduce nausea.

You should NOT take acetaminophen (Tylenol) because when the liver is processing alcohol, it's especially susceptible to acetaminophen's toxic effects. You can eat food, drink water, and rest. It's boring, but at the moment, time is the only sure cure.

Is A Real Scientific Cure Around the Corner?

This past fall, the Web came alive with articles claiming that scientists are on the verge of developing a hangover-free beer. Unfortunately, a lot of the coverage overstated the science: So far, researchers have merely mixed electrolytes into light beer and showed that this caused less dehydration than normal beer. Because hangovers are the result of a bunch of other factors beyond dehydration, the new-fangled beer's no more of a hangover "cure" than drinking water along with your alcohol.

Other researchers, at Imperial College London, are working on synthetic blend of chemicals that produce the pleasant effects of alcohol with much lower levels of toxicity—which, in theory, could reduce the chance of a hangover. But the research is in very early stages, and given the rigorous approval process for drugs that actually treat diseases, it's easy to imagine that synthetic alcohol would take a while to get approval.

About Joseph Stromberg

Joseph Stromberg was previously a digital reporter for Smithsonian.


Footnotes

Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.4938186.

Published by the Royal Society. All rights reserved.

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Understanding alcohol's damaging effects on the brain

While alcohol has a wide range of pharmacological effects on the body, the brain is a primary target. However, the molecular mechanisms by which alcohol alters neuronal activity in the brain are poorly understood. Participants in a symposium at the June 2010 annual meeting of the Research Society on Alcoholism in San Antonio, Texas addressed recent findings concerning the interactions of alcohol with prototype brain proteins thought to underlie alcohol actions in the brain.

Proceedings will be published in the September 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Alcohol is the most common drug in the world, has been used by diverse human communities longer than recorded history, yet our understanding of its effects on the brain is limited when compared to other drugs," said Rebecca J. Howard, a postdoctoral fellow at The University of Texas at Austin Waggoner Center for Alcohol & Addiction Research and corresponding author for this study.

Howard explained that neuroscientists have discovered how marijuana, cocaine, and heroin each bind to a special type of protein on the surface of brain cells, fitting like a key into a lock to change that protein's normal function. Yet alcohol has special properties that make it difficult to characterize its lock-and-key binding in detail, for example, alcohol is much smaller than other drugs, and appears to interact with several different types of proteins.

"The adverse effects of alcohol abuse are devastating on a personal level and on a societal level," added Gregg Homanics, a professor of anesthesiology and pharmacology & chemical biology at the University of Pittsburgh. "Alcohol abuse costs our society more than the costs of all illegal drug abuse combined. For many years, most investigators thought that alcohol exerted nonspecific effects on the brain and simply perturbed neuronal function by dissolving in the membranes of nerve cells. However, our understanding of alcohol action has dramatically shifted in the last 10 to 15 years or so. There is now solid experimental evidence that alcohol binds in a very specific manner to key protein targets in the brain to cause the drug's well known behavioral effects. This review summarizes some of the most recent research."

Some of the key points were:

    Combining X-ray crystallography, structural modeling, and site-directed mutagenesis may be better suited to studying alcohol's low-affinity interactions than traditional techniques such as radioligand binding or spectroscopy.

"One major problem in studying alcohol binding to brain proteins is that the alcohol key does not fit very tightly into any particular protein lock," said Howard. "That is, alcohol has a 'low affinity' for proteins, compared to how other drugs interact with their own protein targets. We think this is one reason it takes such a large quantity of alcohol to affect the brain: whereas users of cocaine or heroin may consume just a few milligrams at a time, a person drinking a shot of strong liquor consumes about 1,000 times that much alcohol (several grams). The low affinity of alcohol for its protein targets [also] makes it difficult to study by traditional methods that rely on detecting stable drug-protein complexes over a long period of time."

"It is now very clear that hydrophobic pockets exist in the structure of various brain proteins and alcohols can enter those pockets," said Homanics. "Alcohols interact with specific amino acids that line those pockets in a very specific manner."

"Different drugs bind to different types of proteins on the surface of brain cells, each fitting like a key, or drug, into a lock, or binding site, on a protein to change its normal function," explained Howard. "Understanding the exact shape of that lock and key helps us to understand how individuals with special mutations may be affected differently by drugs, and can help scientists design new medicines to help people with drug abuse or other problems."

"I feel that there is now overwhelming evidence that specific alcohol binding sites exist on a variety of brain protein targets," added Homanics. "This is significant because we can now focus on defining these sites in greater detail, ultimately at the level of each atom involved. This will allow for, one, a more complete understanding of the molecular pharmacology of alcohol action, two, the discovery of similar sites on other important brain proteins, and three, the rational design of drugs that can selectively target these binding sites."

"Our review summarizes very recent advances in understanding the molecular details of alcohol binding sites, which now include human brain targets, not just metabolic enzymes and receptors from other species," said Howard. "This information will give researchers new opportunities to characterize human mutations and design new medicines. Furthermore, common themes emerging about alcohol binding sites may help scientists identify important binding sites in other important brain proteins."

"In other words," said Homanics, "alcohol exerts its effects via binding sites on target molecules just like all other drugs we know about. There is now solid evidence from several different putative alcohol targets using several different techniques that alcohol interacts with specific brain targets in a highly selective manner. This is particularly important for more senior clinicians and researchers that were trained years ago when the predominant theory of alcohol action was via nonspecific effects on the nervous system." Both Howard and Homanics are hopeful that this research will aid the development of therapies and treatments for individuals with alcohol problems.

"Great progress is being made in understanding how alcohol exerts its effects on the brain at the molecular level," noted Homanics. "Understanding how alcohol affects brain proteins on a molecular level is essential if we are to effectively develop rational treatments to combat alcohol use disorders."

Story Source:

Materials provided by Alcoholism: Clinical & Experimental Research. Note: Content may be edited for style and length.


Glyphosate on Food

One interesting use of glyphosate is to dry wheat before harvest. To help reduce levels of toxic fusarium fungus on wheat, it is good to harvest the wheat as early as possible but you can’t harvest it until it’s dry. So, glyphosate is used to dry (aka kill) the wheat plants so the grain can be harvested. As long as the glyphosate is sprayed after the plants have fully matured, the glyphosate won’t be moved from the plant into the seeds. Here, glyphosate is actually helping farmers prevent a legitimately scary toxin from getting into the food supply. Want to learn more? Check out this video: Wheat School- Timing Pre Harvest Glyphosate Application In Wheat.

With glyphosate being used not only as a herbicide but also as a drying agent, and not just in our lawns but on our food, should we worry about our safety? In short, no. When used properly, glyphosate is quite safe for humans.


Uric acid

Humans also excrete a second nitrogenous waste, uric acid. It is the product of nucleic acid, not protein, metabolism. It is produced within peroxisomes.

  • contribute to the formation of kidney stones
  • produce the excruciating pain of gout when deposited in the joints.

Curiously, our kidneys reclaim most of the uric acid filtered at the glomeruli. Why, if it can cause problems?

  • Uric acid is a potent antioxidant and thus can protect cells from damage by reactive oxygen species (ROS). [Link]
  • The concentration of uric acid is 100-times greater in the cytosol than in the extracellular fluid. So when lethally-damaged cells release their contents, crystals of uric acid form in the vicinity. These enhance the ability of nearby dendritic cells to "present" any antigens released at the same time to T cells leading to a stronger immune response.

Most mammals have an enzyme &mdash uricase &mdash for breaking uric acid down into a soluble product. However, during the evolution of great apes and humans, the gene encoding uricase became inactive. A predisposition to gout is our legacy.

Uric acid is the chief nitrogenous waste of

(It is the whitish material that birds leave on statues.)

These animals convert the waste products of protein metabolism &mdash as well as nucleic acid metabolism &mdash into uric acid.

Because of its low solubility in water, these animals are able to eliminate waste nitrogen with little loss of water.



Comments:

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