Ethanol metabolism Flashcards
1
Q
alcohol dehydrogenase does what
A
makes ethanol go to acetaldehyde
2
Q
if acetaldehyde is not metabolismed it is what to liver
A
toxic
3
Q
ADH1B1 has what Km for ethanol
A
.05 - caucasians
4
Q
ADH1B2 has what Km for ethanol
A
.9 - asians!
5
Q
what is Vmax of ADH1B*2
A
high
6
Q
why do asians have lower risk of alcholism
A
they get sick way more easily from alcohol which protects them from alcoholism
7
Q
ALDH2*2 what is Vmax
A
low
8
Q
what does ALDH2*2 with low Vmax mean
A
acetaldehyde toxicity increased
9
Q
why are women more susceptible to ethanol
A
women have more fat and less water than men, b/c there is less water, the alcohol is more concentrated.
10
Q
aldehyde dehydrogenase is where
A
mitochondria
cytosol
11
Q
what is normal version of aldehyde dehydrogenase
A
ALDH2
12
Q
what is Km and Vmax of ALDH2
A
(Km ~ 0.2μM, Vmax 0.60 units/mg)
13
Q
ALDH1 is found where
A
cytosol
14
Q
accumulation of acetaldehyde causes
A
nausea and vomiting
15
Q
ALDH2*2 what is Km and Vmax
A
Km 46μM, Vmax 0.017 units/mg
16
Q
if a person is ALDH2*2 what are the chances they will be alcoholic
A
0 - so far none has been found
17
Q
Disulphiram promotes alcohol avoidance, how?
A
inhibiting ALDH
18
Q
ADH1B*2 is common in
A
asians
19
Q
what does liver do to acetate
A
Acetyl CoA
20
Q
what enzyme turns acetate into acetyl CoA
A
acetyl CoA synthetase
21
Q
acetyl CoA is used to make
A
fat
22
Q
how does a lot of alchol cause damage to liver
A
one way: Liver – ACS-I in cytosol generates acetyl CoA for cholesterol & fatty acid synthesis
23
Q
cytochrome p450 is where
A
ER
24
Q
draw the flow chart from ethanol to acetate
A
pg 4
25
ethanol ingestion, where does it all go
pg 4
26
ADH1 has high affinity for
EtOH
27
ADH4 activity in GI may be related to what
increased cancer risk
28
describe how asians with ADH1B*2 mutation process alcohol
They have a higher Km than cauasians so they have lower affinity for binding ethanol to alcohol dehydrogenase. however, they have a higher vmax so they process it more quickly
29
describe why hapa's get the asian flush
pg 8
30
alcohol is mainly metabolized in cytosol by what
alcohol dehydrogenase
31
when alcohol is processed by alcohol dehydrogenase it becomes what
acetaldehyde
32
if there is a LOT of drinking, what enzyme becomes active
P450 2E1
33
what is function of P450 2E1
metabolizes alcohol to acetaldehyde
34
beside cytosol, where are two minor places ethanol is metabolized
peroxisome
| mitochondria
35
what does MEOS stand for
Microsomal ethanol oxidising system
36
what is function of cytochrome P450 reductase
transfers electrons from NADPH to cytochrome P450 which binds substrate and O2
37
draw out MEOS and function
pg 11
38
if there is too much alcohol consumption, what happens regarding MEOS
consumption initiates MEOS with consequences of acetaldehyde and free radical injury
39
If there is a lot of drinking and therefore more use of ADH & ADLH, what is consequence
ADH & ALDH generates NADH increasing NADH/NAD+ ratio and disrupting cellular metabolism
40
if there is chronic alcohol abuse what happens to liver
90% fatty liver - inhibition of fatty acid oxidation
41
alcohol toxicity comes from
NADH/NAD+
42
aldehyde dehydrogenase is found in
mitochondria
43
what happens to acetaldehyde with alcohol consumption
increased production of it
44
what are properties of acetaldehyde
reactive
45
alcohol consumption leads to deficiency of what vitamin
vitamin B1
46
by increasing NADH/NAD+ ratio, it leads to what
mitochondria are damaged by acetaldehyde and free radicals
47
what does NADH/NAD+ ratio increase do to fatty acids
inhibits oxidation of fatty acids
48
NADH/NAD+ inhibits
TCA cycle
| reverses malate and oxaloacetate so there will not be substrate for citrate synthase
49
how does alcohol consumption cause gout
elevate uric acid in blood
| uric acid in blood b/c it's not excreted as much
50
if there is insufficient diet and too much drinking, what happens
there is insufficient glucose
| induces glucogenesis which relies on pyruvate from lactate, Ala & Leu
51
increased lactate in kidney, what will it do
kidney excrete uric acid, if there is too much lactic acid it will take lactate and put in lumen and rescue uric acid. therefore the people will be internalizing uric acid and develop gout
52
what is affinity of CYPE2E1 for alcohol
low
53
when you use CYP2E1, it is stabilized by
alcohol
54
CYP2E1 is involved in production of
more P450s
55
P450 is involved in what
drug metabolism
56
cytochrome P450 is used to do what
detoxify molecueles. tags oxygen.
57
cytochrome P450 is part of
MEOS
58
many drugs are metabolised by
cytochrom P450
59
Acetaminophen is active ingredient in
tylenol
60
what happens to acetaminophen in liver
add glucuronate or SO4 (Pg 17)
61
alcohol induced hepattiis
formation of aducts with AAs ↓ hepatic protein synthesis esp. calmodulin, ribonuclease, tubulin
62
how does alcohol induced hepatitis affect tubulin
tubulin adducts inhibit secretion of serum proteins & VLDL, accumulation draws in H2O -> swelling -> portal hypertension -> disruption of architecture
63
WKS (Wernicke–Korsakoff syndrome)
drinking alcohol and causing vitamin B1 deficiency
64
what are symptoms of WKS
Apathy, memory loss, ataxia, nystagmus
65
when you have B1 deficiency you affect key enzymes where
affect key enzymes in cardiovascular and nervous system
66
ehtanol via cytochrom P450 will produce
acetylaldehyde
67
aldehyde dehydrogenase produces a lot of NADH and interferes with
TCA cycle
68
ethanol processed in liver via
ADH
69
if you drink too much you get what to com ein in lvier
MEOS
70
acetaldehyde can do what negative things in liver
modify aa
bind to microtubules
bind to glutathione (need for reactive oxygen species)
71
Hepatic cirrhosis, describe
liver can be so fatty the belly is fatty
Liver injury is irreversible once cirrhosis develops
enlarged, fatty, fibrotic
as liver function ↓, liver may shrink (Laennec cirrhosis)
Loss of normal liver function
synthesis of albumin, clotting factors etc ↓
urea synthesis ↓, so blood ammonia ↑
bilirubin conjugation & excretion ↓ so deposited in skin, sclera & mucosa -> jaundice
72
if you damage liver what will liver have problems processing
bilirubin - get jaundice, pt has yellow skin/eyes
73
↑NADH/NAD+ ratio turns pyruvate into
lactate
74
↑NADH/NAD+ → lactic acidosis, this means lactate isn't availble for gluconeogenesis, therefore what happens
hypoglycaemia
75
what is CYP2E1 affinity for ethanol
low
76
what becomes involved with higher levels of ethanol consumption
CYP2E1 & MEOS
77
CYP2E1 is stabilized by
alcohol
78
MEOS produces more acetaldehyde than can be
metabolised by ALDH
79
MEOS activity produces more acetaldehyde than can be metabolised by ALDH: what does this lead to?
hepatic injury, tissue damage
80
what happens if drugs are taken with a lot of alcohol consumption
the ethanol can inhibit the metabolism of the drugs, leading to drug toxicity. ex: tylenol.
81
Acetaminophen toxicity can be treated with
N-acetyl cysteine to increase GSH production
82
excess acetaminophen is oxidised by
CYP2E1
83
when excess acetaminophen is oxidised by CYP2E1 what toxic product results
NAPQI
84
NAPQI is metabolised by what
GSH
