S1: alcohol metabolism, oxidative stress & protein + amino acid metabolism

Question 1

Describe the metabolism of alcohol

Answer 1

Alcohol is converted into acetaldehyde (enzyme: alcohol dehydrogenase, converts NAD+ into NADH)
Acetaldehyde is converted into acetate (enzyme: aldehyde dehydrogenase, converts NAD+ into NADH)

Question 2

Explain how the metabolism of alcohol can cause damage to the liver

Answer 2

Acetaldehyde toxicity normally kept to a minimum by aldehyde dehydrogenase (low Km)
Prolonged and excessive alcohol consumption can cause sufficient acetaldehyde accumulation to cause liver damage
Fatty liver, alcoholic hepatitis, alcoholic cirrhosis

Question 3

Explain the mechanism of action of Disulfiram in the treatment of alcohol dependence

Answer 3

Inhibitor of aldehyde dehydrogenase

If patients drinks alcohol acetaldehyde will accumulate causing symptoms of a hangover

Question 4

Describe the production of superoxide radicals by mitochondria

Answer 4

Superoxide is producing by adding electron to molecular oxygen
Important source of other ROS

Question 5

Discuss other reactive oxygen (ROS) and reactive nitrogen (RNS) species

Answer 5

ROS = hydrogen peroxide, hydroxyl radical (most reactive and damaging free radical)
RNS = nitric oxide, peroxynitrite

Question 6

Outline cellular defences against reactive oxygen species

Answer 6

Superoxide dismutase: converts superoxide to H2O2 and oxygen
Catalase: converts H2O2 to water and oxygen
Glutathione: protects against oxidative damage (mechanism explained in another flashcard)
Free radical scavengers: donate an electron to the free radical eg. vitamin C and E

Question 7

Explain the role of oxidative stress in disease states

Answer 7

Galactosaemia: increased activity of aldose reductase consumes excess NADPH -> compromised defences -> crystallin protein in lens of eye denatured (cataracts)
G6PDH deficiency: limits amounts of NADPH -> less protection from oxidative stress -> lipid peroxidation + protein damage (HEINZ BODIES)

Question 8

Explain nitrogen balance & protein turnover

Answer 8

N equilibrium: intake = output
Positive N balance = intake > output (normal state in growth, pregnancy and adult recovering from malnutrition)
Negative N balance = intake < output (never normal)
Protein turnover = all body proteins undergo continuous breakdown and resynthesise

Question 9

Describe how amino acids are catabolised in the body

Answer 9

Removal of nitrogen essential to allow carbon skeleton of amino acids to be utilised in oxidative metabolism
Transamination: swaps the amino group with an oxygen (most use alpha-ketogutarate at the keto acid)
Deamination: liberates amino group as free ammonia

Question 10

Define the terms glucogenic and ketogenic amino acids

Answer 10

Glucogenic amino acid: they can be used to synthesise glucose or glycogen eg. alanine, glycine
Ketogenic amino acid: they can be used to synthesize fatty acids or ketone bodies eg. lysine, leucine
Examples of both: tyrosine, phenylalanine

Question 11

Describe PKU symptoms and its treatment

Answer 11

Deficiency in phenylalanine hydroxylase (autosomal recessive)
Accumulation of phenylalanine in tissue, plasma + urine
Musty smell = phenylketones in urine (phenylalanine converted into phenylketones), hypopigmentation = lack of tyrosine
Treatment: low phenylalanine diet, tyrosine supplements, avoid artificial sweeteners, avoid high protein foods

Question 12

Explain the clinical relevance of measuring creatinine in blood and urine

Answer 12

Breakdown product of creatine & creatine phosphate in muscle
Provides estimate of muscle mass (produced at a constant rate depending of muscle mass)
Indicator of renal function - raised level on damage to nephrons

Question 13

What are the two key aminotransferase enzymes?

Answer 13

Alanine aminotransferase (ALT): converts alanine to glutamate 
Aspartate aminotransferase (AST): converts glutamate to aspartate 
Routinely measured part of liver function test
Particularly high in viral hepatitis, autoimmune liver diseases, toxic injury

Question 14

What are the two mechanisms for the transport of amino acid nitrogen from tissues to the liver for disposal?

Answer 14

Glutamine: ammonia + glutamate = glutamine
Taken to liver/kidney
Cleaved by glutaminase to reform glutamate + ammonia
Liver = urea cycle, kidney = excreted in urine
Alanine: amine groups transaminated to glutamate
Pyruvate transaminated by glutamate to form alanine
Transported to liver, converted back to pyruvate
Amino group into urea cycle, pyruvate used to synthesis glucose

Question 15

Give an overview of the urea cycle

Answer 15

Occurs in liver
5 enzymes
High protein diet induces enzyme levels
Low protein diet represses levels 
Not regulated

Question 16

What diseases does the heel prick test for?

Answer 16

Sickle cell anaemia
Cystic fibrosis
Congenital hypothyroidism
Inborn errors of metabolism eg. phenylketouria, homocystinuria

Question 17

Describe homocystinuria and its treatment

Answer 17

Problem breaking down methionine (autosomal recessive)
Excessive homocysteine excreted in urine (elevated plasma level associated with CVS disease)
Defect in cystathionine B-synthase enzyme
Treatment: low-methionine diet, B12 and folate supplement (promotes conversion back to methionine), avoid milk, cheese, meat, fish, eggs

Question 18

Accumulation of what compound causes a hangover?

Answer 18

Acetaldehyde

Question 19

Explain how glutathione works

Answer 19

Thiol group of cysteine donates electron to ROS
GSH then reacts with another GSH = disulphide (GSSG)
GSSG is then reduced back to GSH by glutathione reductase (catalyses the transfer of electrons from NADPH to disulphide bond)
NADPH is therefore essential

Question 20

Describe how paracetamol is metabolised (overdose) and treatment

Answer 20

Overdose of paracetamol
NAPQI accumulates
Direct toxic effects (oxidative damage to liver cell)
Depletes glutathione
Treatment: acetylcysteine treatment - works by replenishing glutathione levels