Session 1- Alcohol Metabolism And Oxidative Stress Flashcards Preview

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Flashcards in Session 1- Alcohol Metabolism And Oxidative Stress Deck (38):
1

What happens to the majority of alcohol (more than 90 percent?).

The majority of alcohol is metabolised by the liver, the alcohol is oxidised by alcohol dehydrogenase to acetaldehyde and then acetate by aldehyde dehydrogenase. The acetate is then converted to acetyl coA and used in either the TCA cycle or for fatty acid synthesis.

2

What is it which causes a hangover?

When alcohol is oxidised to aldehyde acetaldehyde then aldehyde acetaldehyde is a toxic metabolite, the accumulation causes a hangover.

3

What drug is involved in treating alcohol dependence and how does it work?

Disulfiram it works by inhibiting aldehyde dehydrogenase, therefore acetaldehyde levels build up and cause hangover symptoms- putting people off.

4

What are free radicals?

Atoms or molecules which contain one or more unpaired electrons and is capable of independent existence (normally electrons of atoms/molecules/ions associate in pairs). Free radicals are very reactive and tend to acquire electrons from other atoms, molecules or ions.

5

What are the two main types of damage to DNA caused by reactive oxygen species?

The reactive oxygen species reacts with a base- the modified base can lead to mispairing and hence mutation.

The reactive oxygen species can react with sugar (ribose/deoxyribose) which can cause strand break and then mutation on repair.

6

How can reactive oxygen species cause damage to proteins?

By either affecting the side chains and hence modifying amino acids leading to protein degradation/loss of function/gain of function and protein degradation. The other way is by reacting with the backbone and therefore causing fragmentation and hence protein degradation.

7

Can ROS cause disulphide bond formation?

Yes ROS can cause disulphide bonds to form unnecessarily if ROS takes electrons from cysteines causing misfolding, crosslinking and disruption of function.

8

How do reactive oxygen species cause damage to lipids?

Free radical extracts hydrogen atom from a polyunsaturated fatty acid in the membrane lipid, a lipid radical is formed which can react with oxygen to form a LIPID PEROXYL RADICAL, this is a chain reaction as this lipid peroxyl radical then extracts hydrogen from nearby fatty acids, the hydrophobic environment of the bilayer is disrupted and the membrane integrity fails.

9

What are the sources of biological oxidants?

The sources of biological oxidants are either endogenous or exogenous.
Endogenous:
- Electron transport chain, Nitric oxide syntheses or NADPH oxidised.
Exogenous:
Radiation (cosmic rays/UV light/ X-rays), pollutants, drugs and toxins.

10

How are ROS formed in the ETC?

Occasionally electrons accidentally escape the chain and react with dissolves oxygen to form superoxide, they are meant to pass through the ETC and reduce oxygen to form H2O.

11

How does nitric oxide synthase (NOS) work?
What are the 3 types?

Works by converting ARGININE to CITRULLIINE which then reacts with nitric oxide.
The 3 types are:
INOS: inductively nitric oxide synthase, this produces high NO concentrations in phagocytes for a direct toxic effect,
Enos: endothelial nitric oxide synthase (Signalling)
nNOS: neuronal nitric oxide synthase (signalling).

12

What is nitric oxide?

Nitric oxide has a toxic effect at high levels, it is a signalling molecule for vasodilation, neurotransmission and S-Nitrosylation.

13

What is respiratory burst?

It is a rapid release of superoxide and H2O2 from phagocytic cells, the ROS and peroxynitrite (RNS) destroy invading bacteria, this is part of antimicrobial defence system.

14

There are cellular defences to ROS/RNS, what are they?

Superoxide dismutase (SOD) this converts superoxide to H2O2 and oxygen, it is a primary defence because superoxide is a strong initiator of chain reactions.
THEN
Catalase converts H202 to water oxygen, it is a widespread enzyme and is important in immune cells to protect against the oxidative burst!

15

Glutathione is another cell defence how does this work?

Glutathione is a tripeptide synthesised by the body which protects against oxidative damage, what happens in the thick group of Cys donates electrons to the ROS (reactive oxygen species) the GSH then reacts with another GSH to form disulphide forming GSSG (oxidised form), the GSSG is reduced back to GSH by glutathione reductase which catalysts the transfer of electrons from NADPH to disulphide bonds, NADPH from pentode phosphate pathway is therefore essential for protection against free radical damage.

16

What is the penthouse pathway?

A pathway for protection against free radical damage! It starts from Glucose-6-phosphate and is an important source of NADPH which is required for...
Reducing power for biosynthesis/ Maintenance of GSH levels and detoxification reactions.
It also produces C5 ribose required for the synthesis of: NUCLEOTIDES and hence DNA and RNA.

17

Other than NADPH what else is produced in the penthouse pathway?

CO2 is also produced, a C5 sugar ribose is produces which is needed for the synthesis of nucleotides, DNA and RNA!

18

What is the rate limiting enzyme of the penthouse pathway?

Glucose 6-phosphate dehydrogenase!

19

What are free radical scavengers and give the two examples.

Vitamin E- a lipid soluble antioxidant, important for protection against lipid PEROXIDATION.

Vitamin C- a water soluble antioxidant, it has an important role in regenerating the reduced form of vit E.
They reduce free radical damage by donating hydrogen atom to free radicals.

20

What is a disorder caused by lack of defence of oxidative stress and explain it.

Galactosaemia is caused by a deficiency in URIDYL TRANSFERASE, UDP-GALACTOSE EPIMERASE OR GALACTOKINASE, this means that there will be increased activity of Aldo’s reductase which consumes excess NADPH, this compromised defences against ROS damage which causes the crystallin protein in the lens of the eye denatured causing cataracts.

21

What are Heinz bodies?

They are precipitated haemoglobin which binds to cell membrane and alters the rigidity, increased mechanical stress when the cells squeeze through small capillaries, the spleen removes bounds Heinz bodies results in blister cells.

22

What is the clinical sign of G6PDH deficiency?

Heinz bodies.

23

What are the major nitrogen containing compounds?

Amino acids, proteins, purines and pyridimines (DNA/RNA) and then smaller amounts in porphyrins (haem), creatine phosphate, neurotransmitters.

24

What is creatinine?

Creatine is a useful clinical marker, it is the breakdown product of creatine and creatine phosphate in muscle. It is usually produced at a constant rate depending on muscle mass so therefore provides an estimate of muscle mass. It is also commonly used as an indicator of renal function (raised level-damage to nephrons).

25

What is the reference range for creatinine in excreted urine?

Men: 14-26mg/kg
Women: 11-20mg/kg

26

What is meant by positive and negative N balance?

Positive N balance is where the intake of proteins is greater than the output this increases the total body protein and is a normal state in growth/pregnancy or an adult recovering from malnutrition.

A negative N balance is when the intake is less than the output, there is a net loss of body protein and this is never normal, the causes include trauma infection or malnutrition.

27

What is meant by the protein turnover?

Protein turnover is the balance between protein synthesis and protein degradation. It occurs in a series of stages.

28

What are glucogenic and ketogenic amino acids?

A ketogenic amino acid is an amino acid which can be directly degraded into acetyl coA which is the precursor of ketone bodies, this is in contrast to glucogenic amino acids which are converted into glucose.
Some amino acids are both glucogenic and ketogenic, they are involved in the TCA cycle (intermediates).

29

When does mobilisation of protein reserves occur?

The mobilisation of protein reserves occurs during extreme stress (starvation), they are under hormonal control, insulin/growth hormone causes an increase on protein synthesis while a decrease on protein degradation. Glucocorticoids decrease protein synthesis but increase protein degradation.

30

What syndrome can excessive breakdown of protein occur in?

Cushing syndrome (Caused by excess cortisol) it causes a weakening in skin structure leading to striae formation.

31

What is meant by conditionally essential and essential amino acids?

Essential amino acids is where the amino acids are essential in the diet as they cannot be synthesised in the body, the conditionally essential amino acids are where amino acids are essential at certain times.

32

When are some amino acids conditionally essential?

Children and pregnant women have a high rate of protein synthesis, they are growing, they also require some arginine, cysteine and tyrosine in the diet.

33

What is meant by high and low quality proteins?

Proteins of animal origin is high quality as they contain all the essential amino acids, however proteins do plant origin is generally considered low quality since most are deficient in one or more amino acids, therefore veggies need a wide variety of plant sources.

34

Where do the carbon atoms for non essential amino acids come from?

They are intermediates of glycolysis (C3), the pentose phosphate pathway (C4 and C5) and the kerbs cycle (C4 and C5). Amino groups are provided by other amino acids by the process of transamination or from ammonia.

35

What are the two main pathways which facilitate the removal of nitrogen from amino acids?

Transamination and Deamination. The nitrogen removed from amino acids can either be incorporated into other compounds or excreted from the body as UREA.

36

What occurs in transamination?

Transamination involves aminotransferase enzymes which use alpha-ketoglutarate to funnel the amino group to glutamate, the exception is aspartate aminotransferase which uses oxaloacetate to funnel amino group to aspartate. BASICALLY IT IS THE CONVERSION OF AN AMINO ACID TO A KETOGENIC ACID.

37

The enzymes which catalyse transamination are generally called ‘name’ aminotransferase, what do all aminotransferase require?

The co-enzyme pyridoxal phosphate which is a derivative of vit B6.

38

What are the key aminotransferase enzymes you need to know?

Alanine amino transferase
Converts alanine to glutamate
ALT
Aspartame aminotransferase
Converts glutamate to aspartate.
AST
Plasma ALT and AST levels measured routinely as part of a liver function test, levels are particularly high in conditions which cause extensive cellular necrosis such as:
Vital hepatitis, Autoimmune liver diseases and toxic injury