Protein and amino acid metabolism Flashcards
(26 cards)
Why are creatinine levels measured clinically?
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
how much nitrogen is contained within the proteins of the body?
~2Kg
Describe nitrogen balance in humans (Intake,in,out)
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
describe states of nitrogen balance
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
Describe protein turnover
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
what does glucogenic and ketogenic mean?
glucogenic - can be utilised to produce glucose
ketogenic - can be used to produce ketone bodies
give examples of glucogenic, ketogenic and both types of amino acids
GLB = ALT
glucogenic = aspartate, alanine
ketogenic = Lysine, Leucine
Both : Threonine, Tryptophan
What is the pathological basis of Cushing’s syndrome?
Excess cortisol leads to excessive breakdown of protein
Weakens skin structure leading to striae formation
What are the dietary essential amino acids?
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
why is the removal of nitrogen from amino acids required? what two pathways facilitate this?
1) Allow carbon skeleton to be utilised in oxidative metabolism
2) provide nitrogen for other compounds or excreted in urea
a) Transamination
b) deamination
describe the process of transamination
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
what to aminotranferases are clinically relevant and why?
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
describe process of deamination
- 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+)
what is re-feeding syndrome?
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
what are the risk factors for re-feeding syndrome?
BMI <16
unintentional weight loss >15% in 3-6 months
10 days or more without or little nutritional intake
what is a possible defect of the urea cycle?
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
symptoms and management for defects in urea cycle
Symptoms: Vom,Lethargy,Irritability, Mental ret, Seizures, Coma
management: low protein diet, replace amino acids in diet with keto acids
How is amino acid nitrogen safely transported from tissues to the liver for disposal?
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
what does the heel prick test for?
Sickle cell
Cystic fibrosis
Congenital hypothyroidism
Metabolism
- PKU
- Homocystinuria
- Maple syrup urine disease
whats is PKU?
- deficiency in Phenylalanine Hydroxylase
- accumulation of phenylalanine in the tissue,plasma and urine
- phenylketones in urine = musty smell (pet shop)
treatment for PKU?
low phenylalanine diet enriched with tyrosine
avoid artificial sweeteners
avoid high protein foods
what is the pathway for PKU
phenylalanine — Phenylalanine hydroxylase–> tyrosine
(ENZYME NOT PRESENT)
Phenylalanine —-Transamination—> phenylpyuvate
phenylpyruvate —> phenylacetate, phenyllactate
(accumulation of phenylketones)
What pathways are affected in PKU? causing what symptoms?
Tyrosine used to produce NA,Adren, Dopa, Melanin, Thyroid hormone, protein synthesis
sever intellectual disability developmental delay microcephaly (small head) seizures hypopigmentation
What is homocystinuria ?
autosomal recessive
defect in cystathionine B-synthase most common)
Problem breaking down methionine
excess homocystine
affects connective tissue, muscles, CNS, CVS
