Alcohol Flashcards

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1
Q

Production of alcohol

A
  • ethanol C2H5OH (principal alcohol in nature) is
    produced by alcoholic fermentation of
    carbohydrates
  • grapes ~16% sugar (mainly glucose)
  • produced in over-ripe fruits & by enzymes in yeasts
  • small amount from fermentation in colon
    5
    ie C6H12O6 + NADH + ATP -> 2C2H5OH + NAD+ + 2CO2
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2
Q

Absorption & transport

A
  • readily absorbed throughout entire GIT, including stomach
  • Rate of absorption is affected by concentration
  • transported unaltered in bloodstream
  • oxidised mainly in liver to acetaldehyde and then acetate
  • in liver and peripheral tissues, acetate is subsequently
    converted to acetyl CoA & oxidised via TCA cycle  energy
  • distributed throughout total body water with easy entry through
    cell membranes (due to lipid solubility)
  • Most tissues are exposed to the same alcohol concentration as
    blood
    After one drink
  • if 10 g alcohol is diluted in ~40 litres body water (av adult)
  • reaches peak blood concentration of 0.025 g/100ml
  • permitted limit of blood alcohol for driving is 0.05 g/100ml
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3
Q

Metabolism of alcohol:
On average, people can clear ~ _ g ethanol/ hour from blood.
- women less tolerant of alcohol than men because?
- 3 enzyme systems can oxidize ethanol to acetaldehyde

A

5

  • smaller livers
  • lower total body water
  • higher body fat
  • less ‘first pass’ metabolism by alcohol dehydrogenase in gastric mucosa
  1. Alcohol dehydrogenase (ADH) (cytoplasm)
  2. Microsomal ethanol-oxidising system (MEOS)
    (microsomes, smooth ER)
  3. Catalase, in presence of hydrogen peroxide (peroxisomes)
    minor route < 2%
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4
Q
  1. Alcohol dehydrogenase (ADH)
A
  • major route in most people, requires Zn & NAD+
  • oxidises many alcohols to corresponding aldehydes
  • is saturable
  • is the rate limiting enzyme, requires NAD+
  • high ADH activity depletes NAD+ and results in
    accumulation of NADH with widespread metabolic
    consequences
  • ADH is saturated with substrate at a cellular concentration
    of 15-20 mg ethanol/ 100 ml
  • spill over of ethanol may be metabolised by alternative
    routes, mainly via MEOS in liver microsomes
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5
Q
  1. Microsomal ethanol oxidising
    system (MEOS)
A

Oxidation occurs in microsomes via an electron transport system,
collectively called the microsomal electron transport system
* similar to mitochondrial electron transport
* ATP (and heat) are generated via oxidative phosphorylation
* may explain why conversion to E is less efficient at high alcohol intake
* involves ‘mixed-function oxidase’ enzymes i.e. two substrates are
oxidised simultaneously by molecular O2:
- ethanol is oxidised to acetaldehyde, and
- NADPH is oxidised to NADP+ (i.e. bypasses need for NAD+)
* requires special cytochromes (P-450) which act as intermediate electron
carriers

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6
Q

MEOS is inducible

A

Chronic high alcohol intake stimulates proliferation of
microsomal membranes & induces synthesis of MEOS
enzymes (P450)
* thus hepatocytes can metabolise high ethanol intake
more effectively -> ‘tolerance’
* tolerant people ingest larger quantities with less
intoxication

MEOS oxidises various compounds, so induction by alcohol can accelerate metabolism of other substances
metabolised by same system e.g. steroids, tranquilisers,
methadone
* if drug is taken with alcohol, alcohol competes & reduces
drug clearance & degradation
-> dangerously hi levels i.e. possible drug overdose
(less tolerant)
* if drug is taken without alcohol, prior induction can
accelerate drug degradation
-> lower circulating levels with reduced drug effect (more tolerant)

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7
Q

Alcohol ‘intolerance’

A

Occurs in some individuals with moderate alcohol intake
* marked facial flushing, palpitations, tachycardia, muscle weakness
* may depend on acetaldehyde effects, not ethanol per se
* acetaldehyde stimulates catecholamine release from adrenal
medulla & sympathetic NS (ethanol itself is a CNS depressant)
* 5-10% Caucasians but 60-85% Asians, American Indians
* may result in an aversion to alcohol

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8
Q

Clinical effects of alcohol
Brain & CNS:

A
  • depressive & euphoric effect on mental function
  • incr heart rate & peripheral vasodilation, feeling of warmth
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9
Q

Clinical effects of alcohol
Diuretic effect

A
  • ethanol inhibits the normal response of hypothalamic osmoreceptors
  • decreased output of antidiuretic hormone (ADH) which normally conserves water
  • results in failure to reabsorb water in kidney, possible dehydration
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10
Q

Clinical effects of alcohol
Muscle weakness (progressive with increasing intake)

A
  • ethanol inhibits binding of actin & myosin, interferes with contractility
  • long term: cellular swelling, fatty infiltration, fibrosis
  • cardiomyopathy & congestive heart failure; skeletal muscle atrophy
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11
Q

Clinical effects of alcohol
Increased blood pressure

A
  • similar effect on smooth muscle of arterioles
  • short term 2-3 drinks -> acute incr 10 mm Hg
  • long term -> hypertension & risk of stroke in heavy drinkers
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12
Q

Consequences of excessive intake

A

Acute intoxication
* Hangover: excess alcohol in blood from night before; dehydration
* Chronic alcoholism: dependent or addicted
* Alcohol withdrawal syndrome: regular heavy drinker who stops
* Delirium tremens: hi alcohol in blood for weeks or longer followed by
an accident or illness can trigger
* Dehydration, circulatory collapse, hypothermia, injury

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13
Q
  1. Acetaldehyde toxicity
A

Both ADH and MEOS routes of ethanol oxidation produce
acetaldehyde, which has adverse metabolic effects
* attaches covalently to protein -> protein adducts eg
impaired enzyme activity
* impedes formation of microtubules (eg ER) in liver
cells and causes development of fibrosis -> initiates
events leading to liver cirrhosis (widespread fibrosis,
necrosis)

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14
Q
  1. Lactic acidosis
A
  • both ADH & ALDH use NAD+ as a coenzyme, with formation of
    NADH
  • with high intake of alcohol, NADH accumulates -> shifts
    dehydrogenase reactions towards reduction
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15
Q
  1. Increased lipogenesis
A
  • hi NADH inhibits dehydrogenase enzymes in TCA cycle (isocitrate, a-
    ketaglutarate DH)
  • this slows TCA cycle activity  acetyl CoA accumulates
    -> diverted to FA synthesis
  • accumulation of citrate stimulates acetyl CoA carboxylase
  • rate limiting enzyme for synthesis of FAs from acetyl CoA
  • hence lipid accumulates in tissues where ethanol is metabolised resulting in
  • fatty liver also fatty myocardium, fatty renal tubules
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16
Q
  1. Decreased gluconeogenesis
A

High NADH inhibits conversion of AAs to carbon skeleton

17
Q
  1. Increased vit A requirement
A

high ethanol intake competitively inhibits conversion of retinol to
retinal

High ethanol intake saturates ADH/ RDH so alcohol & retinol
spill over into the MEOS with induction of microsomal enzymes
* MEOS pathway results in synthesis of inactive oxidation products (not retinal)
* this increases the dietary requirement for vitamin A

18
Q
  1. Increased thiamin requirement
A

Acute thiamin deficiency eg binge drinkers who consume large
amt of alcohol and stop eating for 3 or more weeks.
Chronic thiamin deficiency may lead to permanent brain damage.

Characteristics
* peripheral neuropathy, ataxia (jerky walk)
* quiet confusion, nystagmus, loss of recent memory -> reversible if
treat with thiamin (Wernicke’s encephalopathy)
* but if severe, may still be left with extreme loss of recent memory &
irreversible brain lesions (Korsakoff’s Syndrome)

Relatively high incidence of WE in Australia
* thiamin fortification of bread since 1991 as a preventative measure
-> decrease. see Harper et al, 2012 for more

19
Q

Toxicity of alcohol

A

Foetal alcohol spectrum disorders (FAS) > 80g/d during
pregnancy
* Typical facial features
- short nose, small eyes, poor formation of mid face
area, low nasal bridge, small head circumference
* Learning, behaviour and growth problems
* Organ abnormalities e.g. heart or kidneys

Liver disease - chronic intake > 40 - 50 g/d
* enlarged fatty liver
-> hepatitis (inflamed, tender)
-> cirrhosis (widespread fibrosis, necrosis)

20
Q

Alcohol & CHD

A

Some evidence suggests light
to moderate alcohol
consumption is associated with
reduced risk of multiple CV
outcomes

Possible mechanisms:
* alcohol increases HDL
* alcohol reduces tendency to thrombosis
* Polyphenolics present in red wine have antioxidant properties that may reduce oxidation of LDL

21
Q

Alcohol and Cancer

A

Convincing - Mouth, pharynx & larynx, Oesophagus, Colorectum (men), Breast

Probable - Liver, Colorectum (women

22
Q

What is standard drink

A

light beer - 425ml
mid strength beer - 375ml
full strength beer - 285ml
regular cider - 285ml
sparkling wine - 100mk
wine - 100ml
fortified wine - 60ml
spirits - 30ml

23
Q

Assessment of alcohol

A
  • Blood alcohol concentration not useful in role of nutritionists and dietitians
  • Serum Gamma glutamyl tranpeptidase (GGT)
  • Raised by intake of alcohol. Also raised in liver disease and with other drugs
  • Multiple other liver function tests however used in assessment of liver disease –
    not specific markers of alcohol intake
  • Dietary intake methods – limitations greater than usual
24
Q
A