2 Protein & Amino Acid Metabolism Flashcards
Identify two major nitrogen containing compounds found in the body
- Amino acids (proteins)
- Purines + Pyrimidines (DNA / RNA)
Identify three minor nitrogen containing compounds found in the body
- Creatine
- Neurotransmitters e.g. dopamine
- Some hormones e.g. adrenaline
What is creatinine?
Creatinine is a breakdown product of creatine & creatine phosphate in muscle
What does measuring creatinine levels show us?
- -Indicator for renal function= raised is nephrons damaged
- Produced at constant rate and filtered via kidneys into urine
- Provides estimate of muscle mass:
- Creatinine urine excretion over 24h is directly proportional to muscle mass
- Provides estimate of muscle mass:
What is nitrogen balance?
Nitrogen balance is the measure of nitrogen input minus nitrogen output i.e. nitrogen input — nitrogen loss
What is the clinical feature of a positive nitrogen balance?
In what instances in a positive nitrogen balance normal? (3)
- Intake > output
Clinical feature:
- Increase in total body protein
Normal state in:
- Growth, pregnancy or adult recovering from malnutrition
What is the clinical feature of a negative nitrogen balance?
In what instances in a negative nitrogen balance normal?
What may cause a negative nitrogen balance? (3)
- Intake < output
- Net loss of body protein
- Never normal (trauma, infection, malnutrition)
What is protein turnover?
Protein turnover is the balance between protein synthesis and protein degradation
Where do amino acids found in the body come from? (3)
- De novo amino acid synthesis
- Dietary protein
- Cellular protein
Provide an example of the following:
- Glucogenic amino acid
- Ketogenic amino acid
- Both ketogenic and glucogenic amino acid
- Glucogenic amino acid: alanine
- Ketogenic amino acid: leucine
- Both ketogenic and glucogenic amino acid: isoleucine
When are protein stores mobilised? (ie used for energy)
Occurs under extreme stress (starvation)
Describe the hormonal control over the mobilisation of protein reserves
Glucocorticoids stimulate the breakdown of protein to be used for energy
In de novo amino acid synthesis, where do the carbon atoms come from?
(Amino acids that can be synthesised de novo are Non-essential amino acids)
- Intermediates of glycolysis (C3)
- Pentose phosphate pathway (C4 & C5)
- Krebs cycle (C4 & C5)
In the de novo amino acid synthesis, where does the amino group come from?
Amino group provided by:
- other amino acids by the process of transamination
- (transfers an amino group to a ketoacid to form new amino acids)*
- from ammonia
Which compounds are synthesised from tyrosine?
- Catecholamines
- Melanin
- Thyroid hormones
Which compound is synthesised from histidine?
Histamine
Which compound is synthesised from arginine?
Nitric oxide
Which compound is synthesised from cysteine?
Glutathione
Hydrogen sulphide (signalling molecule)
Which compounds are synthesised from tryptophan?
- Serotonin (5HT)
- Melatonin
Which molecules are synthesised from glycine?
- Purines
- Glutathione
- Haem
- Creatine
What has to happen to an amino acid to allow it to be used in oxidative metabolism?
- Removal of amine group
- carbon skeleton used
- Once removed nitrogen can be incorporated into other compounds or excreted from body as urea*
What are the two main pathways that facilitate removal of nitrogen from amino acids?
- Transamination
- Deamination
Explain the process of transamination
-
Aminotransferase enzymes
- use a-ketoglutarate
- funnel the amino group to glutamate
-
Aminotransferase enzymes
-
Exception to rule is Aspartate Aminotransferase
- uses oxaloacetate
- funnel amino group to aspartate
-
Exception to rule is Aspartate Aminotransferase
Which aminotransferase enzymes are measured routinely as part of liver function test?
- Alanine aminotransferase (ALT) which converts alanine to glutamate
- Aspartate aminotransferase (AST) which converts glutamate to aspartate
High plasma AST and ALT levels are associated with which conditions? (extensive cellular necrosis)
- Viral hepatitis
- Autoimmune liver diseases
- Toxic injury
Explain the process of deamination
- Liberates amino group as free ammonia (later converted to urea)
- Mainly occurs in liver & kidney
- Keto acids can be utilised for energy
Several enzymes can deaminate amino acids.
Identify three
- Amino acid oxidases
- Glutaminase
- Glutamate dehydrogenase
What happens to ammonia at physiological pH?
At physiological pH, ammonia (NH3) is rapidly converted to ammonium ion (NH4+)
Ammonia (and ammonium ions) are very toxic and must be removed.
How does this occur?
Ultimately converted to urea or excreted directly in urine
Describe 5 properties of urea
- High nitrogen content
- Non-toxic
- Extremely water soluble
- Chemically inert in humans
- has osmotic role in kidney tubules
What is the urea cycle?
- The urea cycle is a process:
- occurring in liver
- involves 5 enzymes
- It is used to dispose of ammonia
Cycle=inducible NOT regulated
Explain how a high/low protein diet affects the urea cycle enzyme levels
- High protein diet induces enzyme levels (up-regulation)
- Low protein diet or starvation represses enzyme levels (down-regulation)
What is refeeding syndrome?
- Refeeding syndrome is a condition:
- occurs when nutritional support given to severely malnourished patients
- Ammonia toxicity significant factor (urea cycle down regulated)
What are the risk factors for refeeding syndrome?
- BMI < 16
- Unintentional weight loss > 15% in 3-6 months
- 10/more days with little or no nutritional intake
What are the effects of autosomal recessive genetic disorders caused by deficiency of one of enzymes in the urea cycle? (1 in 30,000 live births)
- Hyperammonaemia
- Accumulation/excretion of urea cycle intermediates
What does the severity of defects in the urea cycle depend on? (2)
- Nature of defect
- Amount of protein eaten
What are the symptoms of genetic disorders due to defects in the urea cycle?
- Vomiting
- Lethargy
- Irritability
- Mental retardation
- Seizures
What is the management for autosomal recessive disorders due to defects in the urea cycle?
- Low protein diet
- Replace amino acids in diet with keto acids
Why do ammonia levels need to be kept (relatively) low? (BLOOD: 25-40 µmol/L)
- Ammonia is readily diffusible and extremely toxic to brain
Identify 5 toxic effects of ammonia
- Interference with amino acid transport and protein synthesis
- Disruption of cerebral blood flow
- pH effects (alkaline)
- Interference with metabolism of excitatory amino acid neurotransmitters e.g. glutamate and aspartate
- Alteration of the blood–brain barrier
Two mechanisms are utilised for the safe removal of ammonia from tissues for disposal.
In 4 steps, outline the use of glutamine
⇒ Ammonia combines with glutamate to form glutamine
⇒ Glutamine transported in blood to liver /kidneys
⇒ Cleavage by glutaminase to reform glutamate and ammonia
⇒ Ammonia fed into urea cycle (liver) / excreted directly in urine (kidneys)
Two mechanisms are utilised for the safe removal of ammonia from tissues for disposal.
In 5 steps, outline the use of alanine
⇒ Ammonia combines with pyruvate to form alanine
⇒ Alanine transported in blood to liver
⇒ Conversion to pyruvate by transamination
⇒ Amino group fed via glutamate into urea cycle for disposal as urea
⇒ Pyruvate is used to synthesise glucose
Identify 7 clinical conditions which can be detected by the heel prick test.
- Sickle cell disease
- Cystic fibrosis
- Congenital hypothyroidism
- Phenylketonuria (PKU)
- Homocystinuria
- Maple syrup urine disease
- Isovaleric acidaemia (IVA)
What is phenylketonuria? (PKU)
-
PKU:
- common inborn error of amino acid metabolism
- due to an autosomal recessive deficiency in phenylalanine hydroxylase
- Phenylalanine accumulates in the tissue, plasma & urine
- presents with phenylketones in urine (musty smell)
-
PKU:
Outline the treatment of phenylketonuria
- Strictly controlled low phenylalanine diet
- Avoid artificial sweeteners (contain phenylalanine)
- Avoid high protein foods such as meat, milk, and eggs
- Enrich diet w./ tyrosine
Identify 5 symptoms of PKU (if left untreated)
- Severe intellectual disability
- Developmental delay
- Microcephaly (small head)
- Seizures
- Hypopigmentation
Illustrate the affected pathways in PKU
What is homocystinuria?
-
Homocystinuria:
- Autosomal recessive disorder
- commonly due to a defect in cystathionine β-synthase leading to an inability in breaking down methionine
- Excess homocystine (oxidised form of homocysteine) is excreted in urine
-
Homocystinuria:
Which tissues/systems are affected in homocystinuria?
- Connective tissue
- Muscles
- CNS
- CVS
Outline the treatment of homocystinuria
- Low-methionine diet
- Avoid: milk, meat, fish, cheese, eggs and nuts
- Supplements: cysteine, Vit B6, Betaine, B12 & Folate
Illustrate the affected pathways in homocystinuria
Accumulation of methionine and homocysteine causes symptoms
What happens to free amino acids found in the body (what are they used for)?
- Synthesis- cellular proteins
- Energy (glucogenic/ketogenic)
- Excreted in urine (urea)
List the 9 essential amino acids (cannot be synthesised by the body):
(If Learnt This Huge List May Prove Truly Valuable)
- Isoleucine
- Leucine
- Threonine
- Histidine
- Lysine
- Methionine
- Phenylalanine
- Tryptophan
- Valine
Under what circumstances are certain amino acids conditionally essential?
Times- rapid protein synthesis
eg Pregnancy/children
Arginine,tyrosine,cysteine
What coenzyme do all aminotransferases require?
- Pyridoxal phosphate (Vitamin B6 derivative)
Where in the body are amino acids processed to be used for energy?
Liver
How do we treat a patient at risk of developing refeeding syndrome?
Re-feed @ 5-10kcal/kg/day
Raise gradually
Differentiate between Cysteine, Cystine, Homocysteine and Homocystine
What and why are some of the symptoms of homocystinuria and Marfan’s syndrome similar?
- Excess homocysteine- damages collagen and elastic fibres (binds to lysine residues in proteins)
- eg Lens dislocation and skeletal deformities
How do the symptoms of marfan’s and homocystinuria differ?
Metabolites of methione=toxic to neurones
NEUROLOGICAL DYSFUNCTION not seen in Marfan’s
