Amino Acid Metabolism Flashcards
Definition of turnover
Continual renewal/replacement of protein
Definition of amino acid pool
Mixing and exchange with other free AA distributed throughout the body
Definition of oxidative deamination
Generates a ketoacids and other oxidized products from amine containing compounds in the liver
Definition of transamination
Transfer of an amino group from 1 molecule to another, especially from an amino acid to a ketoacid
Definition of glucogenic
Amino acids that can be converted into glucose through gluconeogenesis
Definition of ketogenic
Production of ketone bodies from amino acids through ketogenesis
Definition of ornithine
Cyle of biochemical reactions that produce urea from ammonia
Definition of hyperammonaemia
Excess of ammonia in the blood, can lead to brain injury and death
Function of amino acids
Build
- protein
- NT synth
- creatine
- carnitine
- haem
- purine, pyramidine
Source of blood glucose
Protein turnover 300-400g/day
Difference in half lives of structural proteins and enzymes
Variable
- Structural; proteins => HL of years
- Enzymes, hormones => HL of minutes
Describe the amino acid pool
Mixture of AA in the cell, blood, extracellular fluid Consists of -turnover of body protein -intake of dietary protein -synthesis of non essential AA
Protein requirements (50-70g/day)
Cannot be stored so excess removed as urea
Name the 10 essential AA
Valine Methionine Histidine Lysine Phenylalanine Leucine Isoleucine Threonine Tryptophan Arginine
Describe the nitrogen balance
N intake = N excretion
Rate of body protein synthesis = rate of protein degredation
Positive nitrogen balance
When would this occur
During normal growth in children
In convalescence after serious illness
After immobilization after an accident
In pregnancy
Negative nitrogen balance
When would this occur
Why is this bad?
In starvation
During serious illness
Late stages of some cancers
In injury and trauma
Must be corrected and not be prolonged, otherwise there will be irreversible loss of body tissue and death
Pathways of amino acid degredation in most cellular proteins
Ubiquitin system => 20 AA
Pathways of amino acid degradation in foreign or exogenous proteins
Old/damaged sub cellular organelles
Taken into vesicles by endocytosis/autophagocytosis, vesicles fuse with lysosomes
Proteolytic enzymes degrade proteins => AA
Starvation and hormones, cortisol increases rates of protein breakdown in muscle
Oxidative deamination general formula
Where does this occur
What is the most important AA in deamination
AA + NAD+ + H2O <=AADH=> ketoacid + NH4+ + NADH
Only occurs in the liver mitochondria
Glutamate is the only AA with an active DH
Glutamate + NAD+ + H2O <=GDH=> Oxoglutarate + NADH + NH4+
Transamination general formula
Where does this occur
What can happen after transamination
Amino acid 1 + Ketoacid 2 <=amino transaminase=> Amino acid 2 + Ketoacid 1
Takes place in cytoplasm of all tissues
AA transported to liver as glutamate => deamination
AA + oxoglutarate <=> keto acid + glutamate
What are the 2 types of oxoacid that can arise
Why are there 2 outcomes
Metabolised by TCA
- if from a glucogenic AA => glucose in the liver via pyruvate/oxaloacetate
- if from a ketogenic AA => fat/KB from ACoA
Reaction of pyruvate => ACoA is irreversible
What are the 2 ketogenic AA
What are the 4 ketogenic/glucogenic AA
Ketogenic
- Leucine
- Lysine
Keto and glucogenic
- Threonine
- Phenylalanine
- Tryptophan
- Isoleucine
What are the 4 most important amino acids in nitrogen transport
Alanine
Aspartate
Glutamine
Glutamate
Why is alanine important in nitrogen transport
Alanine + a ketoglutarate <=ALT=> Pyruvate + Glutamate
Glutamate can take part in oxidative deamination
Alanine transported via blood => liver in gluconeogenesis
Why is aspartate important in nitrogen transport
Aspartate + a ketoglutarate <=AST=> Oxaloacetate + Glutamate
Glutamate can take part in oxidative deamination
Involved in urea cycle
Why is glutamine important in nitrogen transport
Carry 2NH3 => liver => urea
Deliver NH4+ => kidney for pH regulation
Formed from glutamate
Why is glutamate important in nitrogen transport
To liver => deamination
Converted to glutamine for safe NH3 excretion
Glutamine metabolism
Glutamine => Glutamate
Glutamate => Glutamine
Glutamine =glutaminase + H2O=> glutamic acid + NH3
Glutamic acid =glutamine synthase + ATP + NH3=> Glutamine + ADP + Pi
The urea cycle
Location?
Location of each reaction?
IN THE LIVER
MITOCHONDRIA NH4+ + CO2 + 2ATP =Carbomoyl phosphate synthase=> carbomoyl phosphate + 2 ADP + Pi
MITOCHONDRIA Carbonyl phosphate + Ornithine =Ornithine transcarbomoylase=> Citrulline
CYTOSOL Citrulline + Aspartate =Argininosuccinic acid synthase=> Arginosuccinate
CYTOSOL Arginosuccinate =Argininosuccinase=> Arginine + Fumarate (lost)
CYTOSOL Arginine =Arginase=> Ornithine + urea (lost)
End products of nitrogen metabolism Protein Creatine phosphate DNA, RNA pH control
Protein => urea
Creatine phosphate => creatinine
DNA, RNA => uric acid
pH control => ammonia
What happens in the impaired conversion of NH3 => urea
Causes?
Symptoms
Prognosis
Hyperammonaemia
Due to
- reduction in catalytic activity of urea cycle enzymes
- liver failure (viral hepatitis, ischaemia, cirrhosis)
Neurotoxic, involves cell death
Leads to cerebral oedema, coma, death
