WEEK 5: Amino acid metabolism Flashcards
what are amino acids?
Monomeric units for proteins
what is the main source of nitrogen in the body?
dietary protein
what compounds contain nitrogen?
haem, creatine, purines and pyrimidines
what happens to excess dietary amino acids?
not required for protein synthesis can’t be stored (in mammals) & aren’t excreted so are converted to energy metabolites
what are the major metabolic fuels?
glucose and fatty acids
what percentage of energy requirements come from amino acids (in humans)?
10-25%
what are 2 sources of amino acids in the amino acid pool?
dietary protein digestion and synthesis of non-essential amino acids
what are 2 utilisation factors of amino acid pool?
go over slide 5 yellow boxes
what are essential amino acids?
cannot be synthesized by the body; obtained via diet
what are non-essential amino acids?
can be synthesized by the body
what are glucogenic amino acids?
catabolism yields pyruvate or an intermediate of the citric acid cycle
what are ketogenic amino acids?
yields acetoacetate, acetyl CoA or acetoacetyl CoA
what do glucogenic amino acids produce when broken down?
carbon skeletons broken down to glucose precursors
what do ketogenic amino acids produce when broken down?
carbon skeletons broken down to ketone body or fatty acid precursors
where is the major site of aa catabolism?
liver
what is the first stage of aa catabolism?
Deamination/Transamination– removal and conversion of amino group to ammonia or amino group of aspartate
what is the second stage of aa catabolism?
Incorporation of nitrogen from ammonia/aspartate to urea
what is the third stage of aa catabolism?
Conversion of amino acid carbon skeletons (a-keto acids) to one of the 7 common metabolic intermediates
go over and understand slide 9 diagram
what is the name of the enzyme responsible for the removal of the amino group in the initial stages of catabolism?
aminotransferases - these are specific for each amino acid.
what does the aminotransferase require as a coenzyme?
pyridoxal phosphate (vitamin B6)
slide 11 - just learn the bullet points
slide 12 ???
what are the 2 isomeric forms that amino acids occur in?
L- or D-
which isomeric form of amino acids do animals utilise?
L-AA
why are D-AAs broken down?
D-AA’s can interfere with metabolism of L-AA’s
what enzyme breaks D-AAs down?
D-amino acid oxidase (D-AAO)
Catabolism of glucogenic amino acids
produces…(6)
pyruvate
oxaloacetate,
a-ketoglutarate
fumerate or
succinyl-CoA.
slide 15 - what happens and what enzyme? vit B6 is required )
what is aspartate converted to?
oxaloacetate via transamination
what enzyme is required to convert aspartate?
Aspartate aminotransferase (AST). requires B6
what is asparargine converted to? what enzyme? slide 17
how can asparagine be used in the treatment for leukaemia patients?
what is required for the urea cycle?
Glutamate and glutamine are required for the Urea Cycle.
why is glutamate a special amino acid?
can be formed or degraded by aminotransferases or by glutamate dehydrogenase (mitochondrial enzyme). both reactions are reversible
slide 18
what is oxidative deamination?
removal of amino group. Oxygen is being put where the ???what group is. also rpoduces NH4+.
slide 19 - is nad(p) h a product or needed for reaction?
what is glutamine?
Glutamine is a non-toxic, transport form of ammonia from the peripheral tissues (especially important in brain)
how is glutamine produced? what does it require?
In peripheral tissues glutamate is converted to glutamine – Glutamine synthetase enzyme. Requires ATP and free ammonia.
how is glutamine converted back to glutamate?
by enzyme glutaminase - water is needed and ammonia is released
how is a-ketoglutarate produced?
through catabolism of both glutamine and glutamate
methionine is cyclic - what does that mean?
what is methionine convertd into?
homocysteine
what are the 2 “fates” of homocysteine?
- can be converted back to methionine by methionine synthase.
- degraded further into cystiene
Catabolism of ketogenic amino acids produces…(3)
Acetyl-CoA
Acetoacetate
Acetoacetyl-CoA
what are the 2 ketogenic amino acids?
leucine and lysine. Both are essential
what is glucogenesis?
what is ketogenesis?
what is phenylanine converted to?
tyrosine
what is required in the conversion of phenylanine?
phenylalanine hydroxylase
what is tyrosine broken down into?
Hydroxyphenylpyruvate
what is Hydroxyphenylpyruvate broken down into?
homogentisate
what is Phenylketonuria (PKU)?
Autosomal recessive disorder,
high levels of Phenylalanine hydroxlase, low levels of tyrosine
what occurs if Phenylketonuria (PKU) is left untreated?
If untreated, leads to permanent intellectual disability, seizures, delayed development, behavioural problems, & psychiatric disorders
how is Phenylketonuria (PKU) treated?
amino acid restriction via low-protein diet, avoid aspartame, supplementation with Tyrosine, monitor blood
what are the branched chain amino acids?
Valine, Leucine, Isoleucine
how are Valine, Leucine, Isoleucine broken down first step
transamination
how are Valine, Leucine, Isoleucine broken down - second step
oxidative decarboxlyation
go over slide 36 third step!! need to know
maple syrup urine disease, go over
how is MSUD treated?
why is ammonia converted?
Ammonia is produced as a result of amino acid degradation and is potentially toxic – required to be converted into a non-toxic form
what are amino acids broken down into basically?
NH3 is TOXIC
Carbon skeleton
what is NH3 detoxified into?
urea in the urea cycle in the liver
slide 42
where does the breakdown of amino acids occur? double check
muscle, peripheral tissues
slide 44
what does alanine do?
main ammonia transporter produced in muscle due to the high levels of pyrvuate generated
chemical formula of urea contains 2 N atoms. How are they donated?
One of the N atoms of urea is donated by ammonia (GDH & Glutaminase)
the second N atom is donated by aspartate
What 2 roles does glutamate play in the formation of NH3 for urea cycle?
Transamination: the amino group of an amino acid is transferred to α-ketoglutarate to form glutamate
Oxidative deamination by Glutamate dehydrogenase forms free ammonia
learn the reaction of the urea cycle, write down steps - slide 48
how many enzymatic reactions of urea cycle?
5
what are the 5 enzymatic reactions of urea cycle?
2 mitochondria
3 cytosolic
what is a rate limiting step of the urea cycle?
the requirement of hydrolysis of 2 ATP
go up to slide 54
what indicates that the urea cycle needs to be regulated?
Increase in arginine indicates substrate availability i.e. NH3
