Proteins & Amino Acid Metabolism Flashcards
Why is creatinine useful as a clinical marker?
Breakdown product of creatine + creatinine phosphate in muscle = provides estimate of muscle mass, also indicator or renal function (higher = worse)
Explain nitrogen balance
Amount entering (dietary protein 16g) = amount exiting (16g),
AA not incorporated into protein enter AA pool which can be used for protein synthesis or N-containing synthesis
When does nitrogen balance change?
+N balance = preg: more in than out.
–N balance = malnutrition: less in then out
Describe protein turnover
Free AA pool = syntheses proteins, last resort with no energy = liver utilises AA pool = broken to C skeleton + amino group
How are amino acids catabolised?
AA broken to C skeleton + amino group (excreted as urea).
C skeleton is either:
1) glucogenic (gluconeogenesis)
2) ketogenic (ketone bodies)
Give an example of a glucogenic AA
Valine
Give an example of a ketogenic AA
Lysine
Give an example of an AA that is both glucogenic and ketogenic
Phenylalanine
Outline defects in amino acid metabolism
‘inborn errors of met’ = 50 inherited types, treatment = restricting specific AA in diets. Found via heel prick test.
What is PKU?
Phenylketonuria = phenylalanine hydroxylase def
= accum phenylalanine + phenylketones (urine) = no prod of tyrosine,
affected pathways = NA, dopamine, melanin, thyroid hormone, protein synthesis
Outline homocystinurias
Defect in cystathionine beta-synthase = prob breaking down methionine = excess homocysteine
= affects CT, muscle, CNS, CVS
Define glucogenic amino acids
More carbons present = amino acid that can be converted into glucose through gluconeogenesis, and other intermediates of the TCA cycle
Define ketogenic amino acids
When broken down there is only sufficient carbons to form Acetyl-CoA (pre-cursor of ketone bodies)
How is nitrogen removed from AA?
Need to remove so the carbon skeleton can be used for energy prod:
Transamination = swap amine from AA with oxygen of keto group (requires α-ketoglutate = aminotransferase).
Deamination = removes amine as free ammonia (must be able to remove ammonia straight away)
What are ALT and AST?
Alanine aminotransferase (ALT) = converts alanine to glutamate
Aspartate aminotransferase (AST) = Converts glutamate to aspartate
What is the urea cycle?
Liver = allowing amino groups of AA to be disposed of via urea
by the input of CO2, aspartate, glutamate,
controlled by 5 enzymes
What is the link between the urea cycle and refeeding syndrome?
Starved = down regulation of 5 urea cycle enzymes,
sudden feeding = urea cycle now unable to cope with amino groups = toxicity of ammonia
Why is ammonia toxic to cell?
Readily diffusible and toxic to the brain = effects AA transport, pH, neurotransmitters, TCA cycle
How is ammonia metabolised
Glutamate + ammonia = Glutamine = excreted in urea cycle.
Pyruvate + ammonia = alanine = broken back down, pyruvate for energy, ammonia to urea cycle
From which AA is adrenaline synthesised from?
Tyrosine
Which keto acid is used by aminotransferase enzymes to funel the amino group of other AA to glutamate?
Alpha-ketoglutarate
Which aminotransferase enzymes are routinely measured as part of LFTs?
ALT = alanine aminotransferase
AST = aspartate amino transferase
Which AA transports ammonia from peripheral tissue to the liver?
Alanine
What is the diff between transamination and deamination?
Transamination = swap amine from AA with oxygen of keto group (requires α-ketoglutate).
Deamination = removes amine as free ammonia (must be able to remove ammonia straight away)
Why do we need to remove N from AA?
Remove as amino group
To allow C skelton to be used in oxidatve metabolism
What is the purpose of glutamine?
Glutamate + ammonia = glutamine
1) Glutamine by blood to liver/kidneys
2) glutamine cleaved by glutaminase
3) ammonia into urea cycle
