Protein And Amino Acid Metabolism Flashcards
Name a few major nitrogen containing compounds
- amino acids
- proteins
- purines /pyrimidines
- DNA/RNA
What is creatinine and why is it used as a clinical marker ?
- during the day , creatine and creatine phosphate is broken down into creatinine
- usually produced at a constant rate
- filtered by the kidneys into urine
- creatinine urine excretion over 24h is proportional to muscle mass
- also used as an indicator of renal fUnction
What is the reference range of creatinine excreted in urine
Per day ?
Men :14-26 mg/kg
- women : 11-20 mg/kg
What does N equilibrium mean
Nitrogen intake = nitrogen output
- normal state in an adult , where there is no change in total body protein
Positive N balance
Intake > output
- increase in total body protein
- this is often occurs during pregnancy as there is a fetus growing inside or during a growth period or an adult recovering from malnutrition
Negative N balance
Intake < output
- net loss of body protein
- never normal
- causes are often trauma , infection or malnutrition
What are the two outcomes for free amino acids ?
- they enter the liver
1) Amino group (-NH2) removed which then undergoesu deamination in the liver.
2) the rest of the amino acid is used to form part of the carbon skeleton in organic compounds. Amino acids can be categorised into glucogenic or ketogenic amino acids.
What are ketogenic amino acids ?
Ketogenic amino acids are amino acids that go on to form acetyl-coA which is involved in ketogenesis
What are the TWO exclusive ketogenic amino acids ?
1) lysine
2) leucine
What are glucogenic amino acids?
Amino acids that can be converted into glucose via gluconeogensis
What are a few examples of exclusive glucogenic amino acids ?
1) methionine
2) valine
3) glutamate
What are a few examples of amino acids that are both ketogenic and glucogenic ?
- tyrosine
- tryptophan
- threonine
In a 70kg man , what is the energy content of TAGS?
600,000Kj
in a 70kg man , what is the energy content of glycogen ?
4000 KJ
What is the energy content of muscle protein in a 70kg man ?
100,000 KJ
When would we use our protein reserves ?
Occurs during extreme stress ( starvation )
Under what control is the mobilisation of protein reserves
Hormonal
Insulin and growth or one release increases or decreases protein degradation?
Decreases
Insulin and growth hormone increases or decreases protein synthesis
Increases
Glucocorticoid(cortisol) release increases or decreases protein synthesis
Decreases
Glucocorticoids(cortisol) increases or decreases protein degradation?
Increases
What is the cause of Cushing syndrome
Excessive breakdown of protein which is caused by excess cortisol which weakens the skin
For the amino acids that are produced in the body ( non-essential AA) , where do they obtain their carbon atoms from ?
- pentose phosphate pathway ( C4 , C5)
Krebs cycle ( C4 , C5)
intermediated of glycolysis ( C3)
Tyrosine is important for the synthesis of …
Catecholamines
- melanin
- thyroid hormones
- dopamine
What are the two main pathways that facilitate the removal of nitrogen from amino acids ?
1) deamination
2) transamination
What is transamination
A chemical reaction where the amine group on an amino acid is exchanged with a keto group of another compound
What are the two key aminotransferase enzymes
1) alanine aminotransferase
2) aspartate aminotransferase
What is the function of alanine aminotransferase ?
Converts alanine to glutamate
What is deamination ?
Removal of an amino group from an amino acid to form ammonia , at psychological pH ammonia is converted into NH4+
- mainly occurs in the liver and kidney
- a few enzymes that can demaminate amino acids are : glutamate dehydrogenase , glutaminase , amino acid oxidases
What are a few characteristics of urea ?
- high nitrogen content
- non-toxic
- extremely water soluble
- chemically inert in humans
- most urea is excreted in urine via kidneys
-
What is the urea cycle ?
Occurs in the liver
- involves 5 enzymes
- converts ammonia into urea
- not regulated
High protein diet induces/represses enzyme levels in urea cycle ?
Induces
Low protein diet induces/represses the enzymes in the urea cycle
Represses
- low protein diet also refers to starvation period
What is redeeming syndrome?
This occurs when nutritional support ( eg high protein content) is given to someone severely malnourished
- due to malnourishment , enzymes that form part of the urea cycle are repressed. Thus feeding a malnourished person a lot of protein would result in toxic levels of ammonia in the body as ammonia cannot be broken down into urea.
- in order to prevent this , re feed patient 5-10kcal/kg/day. Raise gradually to full needs within a week.
What are symptoms of refereeing syndrome ?
- BMI below 16
- unintentional weight loss of more than 15% within 3-6 months
- 10 days or more with little or no nutritional support
What is one cause of defects in the urea cycle ?
Autosomal recessive genetic disorders caused by a DEFICIENCY of one the enzymes in the urea cycle
- these mutations cause a partial loss of enzyme function
- these deficiencies lead to hyperammonaemia
- accumulation /excretion of urea cycle intermediates
Why is the accumulation of ammonia toxic ?
- pH effects ( because ammonia is alkaline)
2. Alteration of the blood-brain barrier
3. Interference with amino acid transport and protein synthesis
4. Interference with TCA cycle
What are the two mechanisms used for the safe transport of amino acid nitrogen from tissues to the liver for disposal ?
1) glutamine
2) alanine
Outline how amino acid nitrogen is transported to the liver /kidneys as glutamine ?
- ammonia combined with g,Utamaro forms glutamine
- glutamine is transported in the blood to the liver or kidneys where it is cleaved by glutaminase to reform glutamate and ammonia
-
Outline how amino acid nitrogen is transported from tissues to the liver / kidneys ?
- Amine groups transferred to glutamate by transamination
- Pyruvate then transamination 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 whereas Pyruvate is used to synthesise glucose .
What is the heel prick test
Tests a baby for inborn errors in metabolism for example :
1) phenylketonuria ( PKU)
2) maple syrup urine disease
3) Homocystinuria
What is the cause phenylketonuria ? ( PKU)
- autosomal recessive disorder which results in deficiency in phenylalanine hydroxylase due to mutated gene on chromosome 12.
What are the consequences of phenylketonuria?
Accumulation phenylalanine due to phenylalanine’s hydroxylasenot being able to work to convert phenylalanine into tyrosine (which is responsible for production of catecholamines , dopamine , melanin )
- instead , phenylalanine undergoes transamination into phenylpyruvate which forms phenylacetate and phenyllactate ( accumulation of phenylketones)
What are symptoms of phenylketonuria ?
- severe intellectual disability
- developmental delay
- seizures
- hypopigmentation
- microcephaly ( small head)
- inhibits brain development
What is the cause of Homocystinuria?
Autosomal recessive disorder which results in a defect in the cystathione b-synthase most commonly
Explain the biochemical basis of Homocystinuria
Homocysteine is usually converted into cystathionine by cystathione-b-synthase (CBS)
- cystathionine is usually then converted into cysteine.
- homocysteine is converted into methionine - this process is promoted by b12, folate and betaine
- this causes homocysteine to acculmate in the body and methionine to accumulate too.
What are the consequences of Homocystinuria?
- an increase in homocysteine causes damage to collagen and elastic fibres in connective tissue by binding to lysine residues in proteins
- methionine accumulation is toxic to neurones and causes neurological dysfunction
- elevated homocysteine shows to be associated with CV diseases ( pro-thrombotic , atheroma)
How to treat Homocystinuria?
- low methionine diet
- avoid milk , meat , fish , cheese and eggs
- nuts and peanut butter too
- use cysteine , vit B6 , B12 , Folate and betaine as supplements
Aminotransferase enzyme : aspartate aminotransferase
Converts glutamate into aspartate
How can we intervene to limit the effects of phenylketonuria?
Low phenylalanine diet , for example meat , milk , protein
- avoid artificial sweeteners
How can phenylketonuria effect brain development ?
Phenylalanine is a large neutral amino acid , it competes for transport across the blood brain barrier via large neutral amino acid transporter
- excess phenylalanine can saturate this transporter
- levels of other large neutral amino acids would decrease
- this inhibits protein /neurotransmitter synthesis
- brain development affected
What amino acid is likely to have been found at a high concentration in urine in someone who has Homocystinuria ?
Homocystine NOT HOMOCYSTEINE
Why is Marfans syndrome and Homocystinuria similar ?
- Marfan syndrome is a genetic disorder of connective tissue , whereas Homocystinuria results in damage to connective tissue
- have similar symptoms for example lens dislocation , skeletal deformities and elastic tissue problems in the heart.
Will a patient with PKU require a dietary source of tyrosine ?
Yes ,
For example cheese , red wine and seeds eg pumpkin seeds are dietary sources of tyrosine.
