Protein and amino acid metabolism

Question 1

Why are creatinine levels measured clinically?

Answer 1

creatinine urine excretion over 24h proportional to muscle mass - provides estimate of muscle mass

indicator of renal function - raised plasma level and decreased urine level on damage to nephrons

Question 2

how much nitrogen is contained within the proteins of the body?

Answer 2

~2Kg

Question 3

Describe nitrogen balance in humans (Intake,in,out)

Answer 3

Intake: from dietary sources ~16g
In body: Body proteins 2Kg , amino acid pool 16g , N-containing compounds 60g
Out: Loss of hair,skin,nails 2g , N-waste products in faeces and urine ~14g

Question 4

describe states of nitrogen balance

Answer 4

Equilibrium: no change in total body protein, normal state in adults

Positive: Increase in total body protein, normal in growth and pregnancy or in recovery from malnutrition

negative: Net loss of body protein, NEVER NORMAL, causes include trauma,malnutrition or infection

Question 5

Describe protein turnover

Answer 5

In: gain of protein from diet which enter pool of free amino acids

these can be used to synthesise cellular proteins (such as muscle) which in reverse cab be proteolysed back to amino acids

Liver: breaks down amino acids into carbon skeleton and amino group

amino group is converted to urea for excretion in urine
carbon skeleton - glucogenic or ketogenic used in either gluconeogenesis or ketone body production for use in energy production

Question 6

what does glucogenic and ketogenic mean?

Answer 6

glucogenic - can be utilised to produce glucose

ketogenic - can be used to produce ketone bodies

Question 7

give examples of glucogenic, ketogenic and both types of amino acids

Answer 7

GLB = ALT

glucogenic = aspartate, alanine
ketogenic = Lysine, Leucine
Both : Threonine, Tryptophan

Question 8

What is the pathological basis of Cushing’s syndrome?

Answer 8

Excess cortisol leads to excessive breakdown of protein

Weakens skin structure leading to striae formation

Question 9

What are the dietary essential amino acids?

Answer 9

If : isoleucine
Learned : lysine
This : threonine 
Huge : histidine 
List : leucine 
May : methionine 
Prove : phenylalanine 
Truly : tyrosine 
Valuable : valine 

CAT in children and pregnant women due to high rate of protein synthesis. Cysteine, arginine and tyrosine

Question 10

why is the removal of nitrogen from amino acids required? what two pathways facilitate this?

Answer 10

1) Allow carbon skeleton to be utilised in oxidative metabolism
2) provide nitrogen for other compounds or excreted in urea

a) Transamination
b) deamination

Question 11

describe the process of transamination

Answer 11

Amino acid converted into keto acid via amino transferase, in turn alpha-ketoglutarate turned to glutamate
OR
Amino acid converted into keto acid via aspartate aminotransferase, in turn oxaloacetate turned into aspartate

Both require Coenzyme Pyridoxal phosphate a derivative of Vit B6

Question 12

what to aminotranferases are clinically relevant and why?

Answer 12

ALT - alanine to aspartate
AST - glutamate to aspartate

measure as part of liver function test
level elevated in conditions which cause extensive cellular necrosis: viral hep, autoimmune liver disease,toxic injury

Question 13

describe process of deamination

Answer 13

• liberate amino group as free ammonia in liver and kidney
• ammonia very toxic and converted to urea and excreted in urine

enzymes: amino acid oxidases, glutaminases, glutamate dehydrogenase

at physiological pH ammonia converted to ammonium ion (NH4+)

Question 14

what is re-feeding syndrome?

Answer 14

Occurs when nutritional support is given to severely malnourished patients

ammonia toxicity significant factor as urea cycle has been down regulated

re-feed at 5-10 kcal/per kg/day
raise gradually over a week

Question 15

what are the risk factors for re-feeding syndrome?

Answer 15

BMI <16

unintentional weight loss >15% in 3-6 months

10 days or more without or little nutritional intake

Question 16

what is a possible defect of the urea cycle?

Answer 16

Autosomal recessive disorders can result in deficiency of one of enzymes required in urea cycle (1 in 30000 births)

hyperammonaemia (can cause brain injury/death v.toxic)
accumulation/excretion of urea cycle intermediates

Question 17

symptoms and management for defects in urea cycle

Answer 17

Symptoms: Vom,Lethargy,Irritability, Mental ret, Seizures, Coma

management: low protein diet, replace amino acids in diet with keto acids

Question 18

How is amino acid nitrogen safely transported from tissues to the liver for disposal?

Answer 18

Two mechanisms are utilised for the safe transport of amino acid nitrogen from tissues to the liver for disposal

Glutamine
-Ammonia combined with glutamate to form
glutamine
-Glutamine transported in blood to liver or
kidneys where it is cleaved by glutaminase to
reform glutamate and ammonia
-In liver ammonia fed into urea cycle. In kidney excreted directly in urine

Alanine
• Amine groups transferred to glutamate by transamination
• Pyruvate then transaminated by glutamate to form alanine
• Alanine transported in blood to liver where it is converted back to pyruvate by transamination.
• Amino group fed via glutamate into urea cycle for disposal as urea whereas pyruvate is used to synthesise glucose which can be fed back to tissues

Question 19

what does the heel prick test for?

Answer 19

Sickle cell
Cystic fibrosis
Congenital hypothyroidism

Metabolism

• PKU
• Homocystinuria
• Maple syrup urine disease

Question 20

whats is PKU?

Answer 20

• deficiency in Phenylalanine Hydroxylase
• accumulation of phenylalanine in the tissue,plasma and urine
• phenylketones in urine = musty smell (pet shop)

Question 21

treatment for PKU?

Answer 21

low phenylalanine diet enriched with tyrosine
avoid artificial sweeteners
avoid high protein foods

Question 22

what is the pathway for PKU

Answer 22

phenylalanine — Phenylalanine hydroxylase–> tyrosine
(ENZYME NOT PRESENT)
Phenylalanine —-Transamination—> phenylpyuvate

phenylpyruvate —> phenylacetate, phenyllactate
(accumulation of phenylketones)

Question 23

What pathways are affected in PKU? causing what symptoms?

Answer 23

Tyrosine used to produce NA,Adren, Dopa, Melanin, Thyroid hormone, protein synthesis

sever intellectual disability 
developmental delay 
microcephaly (small head) 
seizures 
hypopigmentation

Question 24

What is homocystinuria ?

Answer 24

autosomal recessive
defect in cystathionine B-synthase most common)
Problem breaking down methionine
excess homocystine

affects connective tissue, muscles, CNS, CVS

Question 25

describe pathway of homocystinuria

Answer 25

methionine —> homocysteine

homocysteine—cystathionine B-synthase–> cystathionine —> cysteine
(enzyme not present in disease)

accumulation of methionine and homocysteine causes symptoms of disease (cardiovascular disease association)

Question 26

treatment for homocystinuria?

Answer 26

low methionine diet
avoid protein inc nuts and peanut butter
Cysteine, vit b6, betaine, b12 and folate supplement