Protein and Amino Acid Metabolism Flashcards
What are some nitrogen-containing compounds?
Amino acids Proteins Purines and Pyrimidines Porphyrins (haem) Creatine Neurotransmitters (eg dopamine) Some hormones (eg adrenaline)
What is creatinine?
Breakdown product of creatine and creatine phosphate in muscle
True or False:
Creatinine is usually produced at a constant rate depending on muscle mass (unless muscle is wasting)
True
What is creatine urine excretion over 24h proportional to?
Muscle mass - so provides an estimate
As well as providing an estimate of muscle mass, what is creatinine commonly used as an indicator of?
Renal function (raised level on damage to nephrons)
Which is the normal state of nitrogen balance in adults?
N equilibrium
Intake = output
No change in total body protein
What is positive N balance?
Intake > output
Increase in total body protein
Normal in growth and pregnancy
What is negative N balance?
Intake < output
Net loss of body protein
Never normal
Causes include trauma, infection or malnutrition
What is dietary protein broken down into?
Free amino acids which themselves are broken into the carbon skeleton and amino group
What can the carbon skeleton of the amino acids be used for?
Gluconeogenesis (if glucogenic amino acids)
Synthesis of ketone bodies (if ketogenic amino acids)
What is the amino group of the amino acids used for?
Urea -> urine
What is an example of a glucogenic amino acid?
Alanine
What is an example of a ketogenic amino acid?
Leucine
What is an example of an amino acid that is both glucogenic and ketogenic?
Isoleucine
What is the effect of insulin and growth hormone on protein synthesis/degradation?
Increases synthesis, decreases degradation
What is the effect of glucocorticoids on protein synthesis/degradation?
Decreases synthesis, increases degradation
What is Cushing’s syndrome?
Cushing’s syndrome (hypercortisolism) is a collection of symptoms caused by very high levels of a hormone called cortisol in the body.
What can the weakening of skin structure caused by Cushing’s syndrome result in the formation of?
Striae
What are the 9 essential amino acids?
Isoleucine Lysine Threonine Histidine Leucine Methionine Phenylalanine Tryptophan Valine
Where do carbon atoms for amino acid synthesis come from?
Intermediates of glycolysis, pentose phosphate pathway, Krebs cycle
Where does the amino group for amino acid synthesis come from?
From other amino acids by the process of transamination or from ammonia
What is tyrosine required for the synthesis of?
Catecholamines, melanin, thyroid hormones
What is cysteine required for the synthesis of?
Hydrogen sulphide, glutathione
What is tryptophan required for the synthesis of?
Nicotinamine, seratonin, melatonin
What is histadine required for the synthesis of?
Histamine
What is glutamate required for the synthesis of?
GABA
What is arginine required for the synthesis of?
Nitric oxide
What is serine required for the synthesis of?
Sphingosine
What is glycine required for the synthesis of?
Purines, glutathione, haem and creatine
Why is removal of amino group essential?
To allow carbon skeleton of amino acids to be utilised in oxidative metabolism
Which two main pathways facilitate the removal of nitrogen from amino acids?
Transamination and deamination
What is transamination?
The transfer of an amino group from one molecule to another, especially from an amino acid to a keto acid.
What ketoacid do most aminotransferase enzymes use to funnel the amino group to glutamate?
a-ketoglutarate
What enzyme uses oxaloacetate to funnel amino group to aspartate?
Aspartate aminotransferase
What do all aminotransferases require as a coenzyme?
Pyridoxal phosphate (derivative of vitamin B6)
What are the two key aminotransferase enzymes?
Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)
What does alanine aminotransferase do?
Converts alanine to glutamate
What does aspartate aminotransferase do?
Converts glutamate to aspartate
What can plasma ALT and AST levels measure?
Liver function
When are ALT and AST levels particularly high?
Viral hepatitis, autoimmune liver diseases, toxic injury
What is deamination?
Liberation of amino group as free ammonia
Where does deamination mainly occur?
Liver and kidney
What are some enzymes that can deaminate amino acids?
Amino acid oxidases, glutaminase, glutamate dehydrogenase
At physiological pH, what is ammonia rapidly converted into?
Ammonium ion
Is urea water soluble?
Yes
Where does the urea cycle occur?
Liver
How many enzymes does the urea cycle usually involve?
5
When can defects in the urea cycle occur?
Autosomal recessive genetic disorders caused by deficiency of one of the enzymes involved in the urea cycle
What can defects in the urea cycle lead to?
Hyperammonaemia, accumulation/excretion of urea cycle intermediate
How would you manage a patient with defects in the urea cycle?
Low protein diet, replace amino acids in diet with keto acids
What are the several potential toxic effects of ammonia?
Interference with amino acid transport and protein synthesis
Disruption of cerebral blood flow
pH flow (alkaline)
Alteration of blood-brain barrier
Interferance with TCA cycle
Interferance with metabolism of some neurotransmitters
How is glutamate utilised for the disposal of ammonia?
Ammonia combined with glutamate to form glutamine - transported in blood to liver or kidneys where it is cleaved by glutaminase to reform glutamate and ammonia. In liver fed into urea cycle, in kidney excreted directly in urine
How is alanine utilised for the disposal of ammonia?
Ammonia combined with pyruvate to form 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. Pyruvate used to synthesise glucose.
What is phenylketonuria caused by?
Deficiency in phenylalanine hydroxylase - accumulation of phenylalanine in tissue, plasma and urine
How is phenylketonuria inherited?
Autosomal recessive (affected gene on chromosome 12)
How is phenylketonuria treated?
Strictly controlled low phenylalanine diet, avoid artificial sweetners, avoid high protein foods
As phenylalanine hydroxylase converts phenylalanine into tyrosine, which pathways are affected in a patient with phenylketonuria?
Noradrenaline, adrenaline, dopamine, melanin, thyroid hormone, protein synthesis
What are homocystinurias caused by?
Problem breaking down methionine - excess homocystine excreted in urine
Defect in cystathionine b-synthase
How are homocystinurias inherited?
Autosomal recessive
What do homocystinurias affect?
Connective tissue, muscles, CNS, CVS
How do you treat homocystinurias?
Low methionine diet
Avoid milk, meat, fish, cheese, eggs, nuts and peanut butter
Give cysteine, vit b6, betaine, b12 and folate supplement
What does cystathionine b-synthase require as a cofactor?
Vit b6
What is elevated plasma homocysteine shown to be associated with?
Cardiovascular disease
Which amino acid is utilised for the transport of ammonia from peripheral tissues to the liver?
Alanine
(Ammonia is used to transaminate pyruvate to produce alanine. The alanine is then transported in blood to the liver where it is converted back to pyruvate by transamination. The amino group is then fed via glutamate into urea cycle for disposal as urea and the pyruvate is used in gluconeogenesis to synthesise glucose which can be fed back to the tissues)
