Nitrogen Flashcards
what is the glucose-alanine cycle for
a process by which amino acids are transported to the liver from muscle
what is going on at the same time as the glucose-alanine cycle? and therefore what all is being formed?
glycolysis
amino acids and pyruvate
what happens in the muscles with amino acids during exercise?
Proteins are broken down into amino acids due to muscle damage
what is pyruvate converted into in muscles
alanine
how is N2 carried safely around the body
mainly glutamine but alanine if coming from muscle
where is alanine (or glutamine) transported in the blood to?
the liver
once in the liver what is Alanine converted to?
back to pyruvate and then in turn glutamate is produced as alpha ketoglutarate donates amino group to alanine
N2 from glutamate feeds into urea cycle as ammonia and binds with carbomoyl phosphate
once glutamate is produced in liver what happens to it
it can be excreted and feed into the urea cycle
it is excreted as NH4+ ammonia (N2 within it)
this later forms urea in the urea cycle
carbon skeleton is left- pyruvate
what 3 places can N2 come from in the body that feed centrally back to glutamante
alanine from muscles
amino acids from diet
other tissues in the body in form of glutamine
what molecule re-captures ammonia in the urea cycle? what does this produce? and what does the recapturing of ammonia prevent in the body?
carbamoyl phosphate and it produces citrulline
build of ammonia in the blood which can cause toxicity and result in brain damage
what is the second nitrogen acquiring reaction in the urea cycle? ie the second entry of N2
aspartate entering the urea cycle
what is the first nitrogen acquiring reaction in the urea cycle?
nitrogen coming from glucose alanine cycle as ammonia. Binds with carbomyl phosphate and it produces citrulline.
what happens to carbon skeletons (ie left over molecule once nitrogen has been removed)
they become major metabolic intermediates
can be glucogenic (gluconeogenesis) or ketogenic (C.A.C)
glucogenic intermediates
amino acids that feed into gluconeogenesis
ie produce glucose or glycogen in the liver (C.A.C)
ketogenic intermediates
amino acids that feed into acetoacetate (a principle ketone body) or acetyl CoA
ie they produce ketone bodies, acetyl CoA doesn’t enter the C.A.C as no NET synthesis of oxaloacetate
can amino acid carbon skeletons be ketogenic and glucogenic? if so examples
yes
isoleucine, tyrosine and phenylaline
Nitrogen in the atmosphere
N2- ammonia- nitrite- nitrate which can then be taken up by plants and microbes
Humans cannot fix nitrogen
how do humans conserve the N2 they have as they cannot fix nitrogen?
a process called transamination
the movement of amino groups between molecules (recycle it)
transamination principles
no loss or gain of N2 just movement
if you put an amino group on a ketone you get an amino acid
readily reversible
what is needed to enable transamination to be readily reversible?
enzymes- transaminases
these participate in synthesis and degradation of amino acids
what do transaminases rely on
Pyridoxal phosphate cofactor (PLP)
need this bound to them to assist catalysis
which vitamin is PLP made from
Vitamin B6
what is L-glutamine’s purpose
temporary storage of nitrogen
can donate an amino group when needed for biosynthesis
diagnosis: how does the presence of aminotransferases in the plasma help?
indicates cell damage - breakdown of proteins/amino acids
which enzymes are particularly useful in diagnosis
AST and ALT- especially liver disease
when does Amino acid oxidation occur- in which 3 circumstances?
to degrade leftover amino acids from normal protein turnover
to degrade dietry amino acids that exceed body’s protein synthesis needs
to break down and supply precursors for carb production during period of starvation etc
what are inherited metabolic disorders?
Group of genetic diseases involving metabolic defects
typically result in deficiencies of key enzymes
what is an example of a urea cycle disorder
OTC- sex linked inheritence
characterised by hyperammonaemia
what are examples of amino acid disorders
PKU
MSUD
cystinuria
what are examples of carbohydrate disorders
galactosemia
what are 3 effects of enzyme defects
Decreased formation of the product
Accumulation of the substrate
Increased formation of other metabolites
Metabolic disorders and inheritence
most IEMs show autosomal recessive inheritance
what are some common clinical features of inherited metabolic disorders presenting in childhood
Acidosis Failure to thrive Vomiting, refusal of feeds, irritability Central nervous system dysfunction Hypoglycaemia
Phenylketonuria (PKU)
increased Phenylalanine levels due to lacking a key enzyme- this gets converted into toxic side product which can pass through bbb
treatable
build up of metabolite before enzyme
diagnosis of PKU
screening
quantitative amino acid analysis
blood tests
