Identify three major nitrogen containing compounds
- Amino acids
- Purines + Pyrimidines (DNA / RNA)
Identify three minor nitrogen containing compounds
- Neurotransmitters e.g. dopamine
- Some hormones e.g. adrenaline
What is creatinine?
Creatinine is a breakdown product of creatine & creatine phosphate in muscle
Explain how creatinine can be used a clinical marker for renal function
- Produced at constant rate and filtered via kidneys into urine
- Creatinine urine excretion over 24h is 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
Which three concepts revolve around nitrogen balance?
- Nitrogen equilibrium
- Positive nitrogen balance
- Negative nitrogen balance
What are the clinical features of nitrogen equilibrium?
- Intake = output
- No change in total body protein
- Normal state in adult
What are the clinical features of a positive nitrogen balance?
- Intake > output
- Increase in total body protein
- Normal state in growth, pregnancy or adult recovering from malnutrition
What are the clinical features of a negative nitrogen balance?
- 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
Illustrate the pathways involved in protein turnover
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?
Occurs under extreme stress (starvation)
Describe the hormonal control over the mobilisation of protein reserves
In de novo amino acid synthesis, where do the carbon atoms come from?
- 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 or from ammonia
Which compounds are synthesised from tyrosine?
- Thyroid hormones
Which compound is synthesised from histidine?
Which compound is synthesised from arginine?
Which compound is synthesised from cysteine?
Which compounds are synthesised from tryptophan?
- Serotonin (5HT)
Which molecules are synthesised from glycine?
Why does nitrogen have to be removed from amino acids in protein metabolism?
- Essential to allow carbon skeleton of amino acids to be utilised in oxidative metabolism
- 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?
Explain the process of transamination
- Most aminotransferase enzymes use a-ketoglutarate to funnel the amino group to glutamate
- Exception to rule is aspartate aminotransferase which uses oxaloacetate to funnel amino group to aspartate
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?
- Viral hepatitis
- Autoimmune liver diseases
- Toxic injury
Explain the process of deamination
- Liberates amino group as free ammonia
- Mainly occurs in liver & kidney
- Keto acids can be utilised for energy
Several enzymes can deaminate amino acids.
- Amino acid oxidases
- Glutamate dehydrogenase
What happens to ammonia at physiological pH?
At physiological pH, ammonia (NH3) is rapidly converted to ammonium ion (NH4+)