Alcohol I Flashcards
what are the main components of the structure of alcohol?
it has a methyl CH3 group on one end and a string of carbons and then an hydroxyl (OH) group on the other end
What two things need to be present for alcohol production and what is the yielding product? (summarized)
yeast needs to be present to ferment sugars (first converted to glucose, then pyruvate) into ethyl alcohol and carbon diozide
What do the yeast use in the alcohol production pathway? how much alcohol can they produce?
yeast use this pathway to generate NAD+ which is a cofactor used in glycolysis to make ATP .. so yeast use this pathway to make energy for themselves
they can only make up to 15% ethanol before the ethanol kills it
what is the fermentation process steps?
- you start with 6 carbon glucose
- in the process of glycolysis, 2 ADP make 2 ATP and use cofactor NAD+ to make 2 NADH, and produce 2 pyruvate molecules each made of 3 carbons
- Then pyruvate decarboxylase removes a co2 from the pyruvates (sends it off into atmosphere in form of bubbling) and produces 2 acetaldehyde
- the acetaldeyde gets formed into 2 ethanols via alcohol dehydrongenase which uses 2 NADH cofactors to make 2 NAD+ which is used up again in glycolysis
what is gut fermentation syndrome?
its when a bacteria called saccharomyces cereisaiae causes yeast to form ethanol in your gut
how many onzes in one standard drink in canada?
0.6 oz of ethanol
how many grams of ethanol are in one ounce given that theres 22.3 grams of ethanol in an ounce?
22.3g/oz X 0.6oz = 13.38 grams
how is alcohol absorbed in the stomach?
proteins within the stomach decrease alcohol absorption but the pH of the stomach has nothing to do with the absorption of alcohol
how is alcohol absorbed in the small intestine?
theres more absorption at the level of the small intestine after it leaves the stomach, thats why if you drink on a fuller stomach absorption will take more time before empying out into the small intestine
- alcohol with co2 bubbles also increase absorption by increasing transit from stomach to small intestine
most of the absorption happens at the small intestine
What is the Mellanby effect?
indicates acute tolerance to the effects of alcohol (happens right away)
shown in graph of ethanol absorption in humans
humans appear more impaired approx 30 minutes after dose administration with a mean BAC of around 68 mg/dl, and describe feelings of euphoria, happiness, friendly..etc.. but then at around an hour after dose administration they hit the peak BAC level (83 mg/dl) and then start dropping in BAC% as body starts to metabolize the ethanol. While on its way down, at 68mg/dl the person starts feeling lethargic, sick, grumpy, depressed…etc.. negative moods
this is the Mellanby effect that the same dose differs n behaviour produced depending on whether it is in the rising phase vs. the decreasing phase
what is the biphasic effect of ethanol in animals?
the biphasic effect:
- at low doses, ethanol can increase locomotion and acts as a moto stimulate, this is likely due to increased dopamine levels
- at high doses, it is a sedative/depressant and these seem to be mediated via effects on receptors for GABA and glutamate
what kind of behaviours are disrupted by ethanol in low concentrations?
- at low concentrations complex, abstract, and poorly learned behaviours are disrupted
what kind of behaviours are disrupted by ethanol in high concentrations?
better learned and basic behaviours are affected, as well as motor control
what is acute death from overdose of ethanol typically due to?
respiratory depression, coma or inhalaiton of vomit
what is disinhibition? when does it occur?
inhibitions are reduced
some behaviours are increased because of this like verbal expression, socializing and risky sexual behaviours
disinhibition is linked to increase dopamine levels in the reward pathway
can be seen in most organisms from simple worms to humans
at certain dose
u experience euphoria and happiness and anxiety is diminished
when ur sober ur PFC controls certain thoughts, and words that are innapropriate for the context from coming out but alcohol prevents this and inhibits the inhbitory pathways therefore making them excitatory
How does ethanol increase sociability and decrease anxiety in animal models?
at low doses, ethanol increases social interaction and theres a bigger effect of this in adolscents
ethanol also relieves anxiety when mice are placed in unfamiliar areas and you see more singificant social interaction when alcohol levels increase in adolescents
can be seen as overcoming the inhibitory effects of an unfamiliar environment on social interaction
what is BAC? how is it calculated?
BAC is the blood-alcohol concentration
it is a grams of ethanol per 100ml of blood
so a BAC of 0.08 is 0.08 grams of ethanol in 100ml of blood which is the legal limit
to calculate, you divide the number of grams of ethanol ingested by the volume in which it can distribute
What is the BAC of concentration needed to kill you?
0.4g or 0.5 grams and higher of alcohol per 100ml of blood
why is the BAC of men lower than women for the same amount of alcohol ingested?
men have more water than women which means the ethanol can be more diluted in their system
women have less water so alcohol affects them more
this is because men have more muscles, which retain more water, and women typically have less muscle, and retain less water
how do you estimate blood alcohol concentrations?
first you convert the ounces of alcohol in a standard drink into grams = 13.4 grams
then you figure out how much % of a typical man and typical woman is composed of water. You do this so you can see how much of the ethanol in one drink is diluted in an average person
so an average man is 58.3% water
and an average woman is 48.5% water
Now we want to multipy the % water by the weight of the average male or female to get the total liters of water they store in their bodies
one litre of water weighs 1kg so:
a 200 pound (90.7kg) woman X 0.485 = 44L
a 200 pound (90.7kg) man X 0.583 = 52.9L
Now you need to know how much ethanol in % is in the total liters of water stored in the average man and average woman
- 4g/44L = 0.30g/L = 0.030g/100mL = 0.030% (for a woman)
- 4g/52.9L = 0.25g/L = 0.025g/100mL = 0.025% (for a man)
so for an average woman theres 0.030% alcohol in their body water and for an average man its 0.025% alcohol
now we need to convert this to blood values
blood is 80.6% water so you multiply alcohol-water values by this number to get blood alcohol concentration
- 03 x 0.806 = 0.024 (for women)
- 025 x 0.806 = 0.20 (for males)
these are blood alcohol concentrations
what is the percentage of alcohol metabolized in the liver? how much of it goes unmetabolized?
most of alcohol gets metabolized via first pass metabolism
90% is metabolized by liver
2% excreted unchanged in breath, skin and urine
and some gets metabolized in the stomach
what occurs during the metabolism of alcohol? what are the major enzymes involved? where does it occur? what are two enzymes that pitch in to metabolize alcohol when theres a large amount of ethanol in the liver?
alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) are the major enzymes
most metabolism occurs in the liver but small amounts are metabolized elsewhere like stomach
the enzyme CYP2E1 normally metabolizes less than 20% usually but percentage increases with heavy drinking
catalase (another enzyme) plays a minor role overall. May produce acetaldehyde in the brain, may induce acute increase in alcohol metabolism
CYP2E1, and catalase dont play a big role in metabolism of ethanol unless theres alot and then they speed up the process a bit
when CYP2E1 and catalase start to metabolize more ethanol (usually bc theres lots) they make more acetaldehyde which is toxic to the body
therefore chronic drinkers have higher acetalaldehyde amount
How does the liver metabolism of ethanol show saturation? and what is the reason?
if you give the liver alot of alcohol, it wont metabolize all of it for a while. The ability for enzymes to metabolize ethanol is quickly overwhelmed and not all of it can get metabolized the first time through the liver
the reason for this is because enzymes in the liver need the cofactor NAD+ to work
metabolizing 1 standard drink requires a large quantity of NAD+ and NAD+ isn’t always available in large amounts because other processes in the body require it as well
what does NAD+ limit the availability of metabolism to?
about 8g/hour (one standard drink is 13.8g) so about 2 hours to metabolis one drink
what is the kinetics of metabolism in alcohol?
instead of a proportion of ethanol being removed in a given amount of time, there is a constant amount of ethanol removed in a given amount of time
there is so much ethanol that all enzymes involved in its metabolism are completely occupied and there is no excess capacity in the system
the metabolic pathway operates at a max level with a modest amount of alcohol in the system
regardless of the dose or BAC level, metabolism drops roughly the same amount when metabolized an hour after absorption
what does metabolism depend on? what is the average persons metabolism rate? what is the value of BAC drop her hour after injesting alcohol in Canada for law?
metabolism depends on alcohol expereince. experienced drinkers tend to metabolize more quickly due to metabolic tolerance
the average drinker metabolism rate is 0.017 BAC decline per hour
in canada and in courts, they use 0.015 BAC per hour as the average
so 0.015 grams of alcohol get metabolised per 100 ml per hour
how much BAC drop in an average male and female after an hour?
in an average male:
0.020 (BAC after one drink) - 0.015 (avg. BAC drop in one hour) = 0.005 = 0.005/0.020 = 25% of ethanol left in system to metabolize
in average female
0.024 - 0.015 = 0.009 = 0.009/0.024 = 37.5% ethanol left
after one hour the male has metabolized 75% (100-25) of the single drink, and the female has metabolized 62% (100-37.5)
What do breathalyzers measures? how many parts of ethnaol is in blood compared to lungs?
[alcohol]blood: [alcohol]exhaled breath = 2100:1
so theres 2100 times more concentration of ethanol in blood than in breath
the breathalyzer measures the 1 part of ethanol in breath
the breathalyzer records the amount of non-metabolized ethanol expired from the lungs
which enzymes are involved in metabolism of alcohol? what byproducts do they produce?
ethanol gets formed into acetaldehyde by alcohol dehydrogenase and then acetaldehyde gets formed into non-toxic acetate via aldehhyde dehydrogenase
what happens when you have a mutation in the aldehyde dehydrogenase gene?
you get more build up of acetylaldehyde in the GI tract which is toxic and causes blushing, sweating, and increased risk of esophageal cancer… common in asians
what are the 3 stages of metabolism for ethylene glycol (aka antifreeze)?
first stage: CNS depression –> appears like you’re drunk, can lead to coma
second stage: cardiopulmonary dysfunction –> acidosis (drop in pH of blood) can be fata, and can head to hyperventilation, heart arrythmia and pulmonary edema(swelling in lungs/water in lungs)
third stage: renal dysfunction (kidney failure), urine production stops, can occur few days after contact
30 ml of this can cause death
what are the toxic byproducts formed in ethylene glycol metabolism? what do they do and what enzyme breaks them down?
etheylene glycol is converted to glycoaldehyde by alcohol dehydrogenase, and then glycoaldehyde is further made into to glycolic acid and oxalic acid by ADH as well
glycolic acid acid turns into oxalic acid over time and oxalic acid can bind with calicum to form crystal that precipitate through body including kidneys and lungs
glycolic acid lowers the pH in the blood which can lead to alot of more problems with heart rate etc..
how is methanol (formic acid) metabolised? what are the initial symptoms and then what happens over time? what kind of damage does it do?
formic acid is responsible for optic nerve damage because it disrupts mitochondrial function
as little as 10ml of it can cause blindness and 30ml can cause death
formic acid also produces acidosis by lowering pH of blood
as time passes (6-30hrs) and more is metabolized, the symptoms of vision loss and acidosis become more serious
respiratory failure or sudden resp. arrest are the most common causes of death from methanol.
what is the enyme involved in methanol metabolizm and what are the byproducts?
enzyme involved in making methanol into formaldehyde (DANGEROUS PERSERVATIVE) by alcohol dehydrogenase and then ADH also takes formaldeyde and turns it into formic acid which can cause acidosis and blindness
formic acid is worse than formaldehyde even though they are both dangerous
how is rubbing alcohol metabolised? what enzyme metabolizes it and what are the byproducts? what does it do ?
acetone/isopropanol are CNS depressants
they are safe at low levels
at high levels, they cause vomitting and coma
what is an older way of preventing methanol poisoning? what is a problem with this method?
the older method of preventing posioning is to flood the body with ethanol because ethanol is more favoured to ADH than methanol is, so ADH will bind to all of the ethanol and leave no room for methanol therefore, excreting it out of the system and producing less to little amounts of the dangerous metabolites
the problem with this is that some people cant handle ethanol in large amounts i.e. their liver is messed up or they have other problems so its not a good idea
what is a newer method of preventing methanol and ethylene glycol poisoning?
inhibiting alcohol dehydrogenase with fomepizole, a competitive inhibitor of the enzyme
used in ethylene glycol and methanol poisoning
it has a longer duration of action than flooding the system with ethanol which is good but it is more expensive
minimal adverse effects compared to flooding the system with methanol
