L1 - Alcohol metabolism and oxidative stress

Question 1

Use a4 paper notes and lecture

Answer 1

Yes

Question 2

whar is the recommended alcohol intake limit in units for men and wome in a week?

Answer 2

14

Question 3

what is the toxic intermediate of alcohol metabolism which accumulates causing hangover symptoms?

Answer 3

acetaldeyhde

Question 4

How does excessive alcohol intake lead to a fatty liver AND liver cirrhosis (damage)?

Answer 4

Fatty liver - Excess alcohol metablism leads to excess NADH and acetyl CoA -> increased fatty acid and ketone body synthesis -> increased fat deposition

Liver damage - Excessive prolonged consumption leads to sufficient accumulationg of toxic acetaldehyde which causes liver damage

Question 5

How does disulfiram work in treating alcohol dependence?

Answer 5

It inhibits acdehyde dehydrogenase which metabolises acetaldehyde to acetate -> acetaldehyde builds up giving severe hangovers to put the user off drinking

Question 6

How are reactive oxygen species (ROS’) produced by mitochondria?

Answer 6

Occassionally in mitochondria an electron escapes the electron transport chain in oxidative phosphorylation and reacts with the surrounding oygen to produce a superoxide free radical

Question 7

Which free radical is the most damaging?

Answer 7

OH (hydroxyl free radical) - note remember to put the dot after free radicals

Question 8

nitric oxide is a free radical which can react with a superoxide radical to produce peroxynitrate which is a damaging oxidant but not a free radical. h2O2 (hydrogen peroxide) isn’t a free radical T/F?

Answer 8

T - but it can react with ferrrous iron (fe2+) to make free radicals

Question 9

ROS cause damage via three main mechanisms, what are they?

Answer 9

damage to proteins/damage to DNA/lipid peroxidation (formation of more ROS’)

Question 10

LO - There are four major cellular defences against ROS’, describe three of them and how they work

Answer 10

Free radical scavengers - such as vitamin E which mops up against lipid peroxidation

Superoxide dismutase - converts superoxide to hydrogen peroxide and oxygen

Catalase - Converts hydrogen peroxide to water and oxygen

Glutathione - Works by reacting with ROS’ so that they don’t cause damage elsewhere

Question 11

Name two endogenous sources of ROS’ and two exogenous sources

Answer 11

Endogenous - Electron transport chain/Nitric oxide synthases/NADPH oxidases

Exogenous - UV light/X-rays/pollutants/anti-malarial drugs/herbicides

Question 12

NO is a free radical but also has important endogenous functions, name two

Answer 12

Vasodilation/signalling

Question 13

Our bodies defences use ROS’ to combat bacterial infection. MAcrohpages use a respiratory burst of superoxide and hydrogen peroxide in combatting bacterial infection. The superoxide radical is made by NADPH oxidase, in what disease is there a genetic defect in NADPH oxidase?

Answer 13

Chronic granulomatous disease - patients are thus susceptible to bacterial infections such as pneumonia/impetigo/cellulitis/abcesses etc.

Question 14

What does the pentose phosphate pathway produce?

Answer 14

5 carbon ribose sugars needed for the synthesis of DNA and RNA and importantly it is a big source of NADPH

Question 15

What is the rate limiting enzyme of the pentose phosphate pathway?

Answer 15

Glucose 6-phosphate dehydrogenase

Question 16

How then does Glucose 6-phosphate deficiency result in increased damage from oxidative stress and haemolysis?

Answer 16

G6PDH is required for pentose phosphate pathway -> pentose phosphate pathway is a big source of NADPH -> deficiency thus means less NADPH -> NADPH required for glutathione defence - no glutathione means increased oxidative stress -> cell damage and cross-linking of haemoglobin causes heinz body formation -> haemolysis

Question 17

How does a deficiency in any of the three enzymes important in galactose metabolism cause cataracts?

Answer 17

It causes increased activity of an alternate pathway that uses aldose reductase which uses up NADPH -> NADPH needed for glutathione -> increased vulnerability to ROS stress -> protein damage -> cataracts

Question 18

Paracetomol overdose also causes problems by depleting glutathione, actetylctysteine is the antidote which replenishes glutathione levels, T/F?

Answer 18

T

Question 19

differentiate between glucogenic and ketogenic amino acids

Answer 19

ketogenic - directly makes acetyl-CoA -> funneled into ketone body synthesis

glucogenic - products are funneled into gluconeogenesis