MAPUD Flashcards
maple syrup urine disease is a
rare autosomal recessive disease
MSUD categorized as
metabolic and catabolic disorder
two parts of metabolism
anabolism
catabolism
anabolism
building molecules
catabolism
breaking apart molecules
in mos cases, symtoms of MAPUD begin
a few days after birth.
the primary diagnostic symptom of MAPUD
urine with a distinct sweet aroma , like maple syrup
MSUD affects how many births
1 in 150,000 births
because MSUD is recessive
both copes of a gene must be faulty
MSUD is a
trimer
three genes that could be faulty in MSUD
one on chromosome 19
one one chromosome 6
one on chromosome 1
msud gene on chromosome 19
BCKDHA
BCKDHA makes what
E1-a protein
msud gene on chromosome 6
BCKDHB
BCKDHB makes what
E1-B protein
msud gene on chromosome 1
DBT- makes E2 proteins
E1-α, E1-β, and E2 come together to form
a trimeric enzyme
what trimeric enzyme does
E1-α, E1-β, and E2 form
branched-chain alpha-keto acid dehydrogenase
important note for MSUD
does not follow dominant-negative gene action
it has been proposed that BCKD has
4 subunits, not 3
BCKD
branched-chain alpha-keto acid dehydrogenase
TO GET MSUD YOU MUST
inherit two faulty versions of the same chromosome
_______ catalyzes an irreversible step of the breakdown of three “branched chain” amino acids
Branched-chain α-keto acid dehydrogenase
what branched amino acids are catalyzed by Branched-chain α-keto acid dehydrogenase
valine, leucine, isoleucine
the breakdown of the thee “branched chain” amino acids is a
3 step of 4 step process
failure of BCKD leads to
excess amount of the three amino acids
failure of BCKD leads to byproduct…
alpha-keto acids
keto-acids have
a before the name
mostly, what are valine, leucine, isoleucine used
they are usually used to build the body’s own amino acids
valine, leucine, isoleucine are brok en..
apart for energy in certain instances
what instances are valine, leucine, isoleucine broken down
- starvation/fasting
- fighting illness
- body consumed too much protein
almost all pieces of the breakdown of valine, leucine, isoleucine
end of falling into the Krebs cycle
what is the Krebs cycle
the complex process in which a cell produces energy from glucose
since pieces of breakdown of valine, leucine, isoleucine join…
join cycle late, means they dont generate as much energy as the sugar
Krebs cycle is responsible for
for energy production of cells
what are the krebs cycle pieces that come from the keto acids
Acetyl-CoA, Succinyl-CoA
when valine, isoleucine and their alpha-keto acids accrue in the bloodstream…
they move into cells
when valine, isoleucine and their alpha-keto acids accrue in the bloodstream and move into cells
it is toxic for cells, ecspecially nerve cells `
when the amino acids and their alpha-keto acids move into cells, why is it toxic?
three amino acids and keto acids block entry of other amino acids into the brain (much like in PKU)
having too much of the three amino acids and not enough of the rest leads to
temporary mental retardation, impaired motor control, seizures `
the extra byproducts (keto acids) are someties broken down to
to form sotolon
what is sotolon
a small chemical that smells strongly of maple syrupor fenugreek
how is sotolon excreted
through urine
amino acid breakdown is almost completely carried out where
in the mitochondria of liver cells
1 of the cures for MSUD
complete liver transplant `
why can a complete liver transplant cure MSUD
the new transplant cells do not carry the mutation, and can produce E1-a, E1-b, and E2 correctly
before a liver transplant, people w/ MSUD must
closely monitor their diets to avoid protein
why must ppl w/ MSUD closely monitor their diets to avoid protein before a liver transplant
they should have just enough valine, leucine, and isoleucine to produce their proteins
ppl w/ MSUD undergoing a liver transplant must also
avoid going into starvation mode, usually eat MSUD diet powder
why avoid going into starvation mode (MSUD transplant)
so the body dosen’t break down protein for energy, it must stay in first gear and break down carbohydrates constantly
classifications of MSUD
Acute MSUD, Intermediate MSUD, Intermittent MSUD
Acute MSUD
two amorphic or severe hypomorphic mutations inherited for any one of the pieces f the trimer
In acute MSUD symptoms are
present almost immediately after birth and results in death within the first few months of life unless treated immediately
severe hypomorphic
less than 8% function
intermediate MSUD
one piece of the trimer receives two hypomorphic (8-15% function) mutations.
in intermediate MSUD, function of the trimer
is slow, but still work `
in intermediate MSUD, symptoms begin
in childhood, but when depends on how hypomorphic and patients diet
phosphorylation
adding a phosphate group to the R-chain
phosphorylations generally turn proteins
on or off
phosphorylations are almost always
reversible
kinase
an enzyme that adds a phosphate group
phosphatase
enzyme that removes a phosphate group
kinase and phosphate can both be
on or off switch
less extreme forms of MSUD exist
in mutations of 2 other genes BCKDK and BCKDP `
BCKDK does what
codes for BCKD kinase
what does BCKD kinase do
adds a PO4 to the -3 to BCKD
BCKDP does what
codes for BCKD phosphatase
what does BCKD phosphatase do
removes a PO4 to the -3 from BCKD
in the liver,
BCKDK gene is expressed in cells at very low rates compared to other cells
Why does BCKDK code for the off switch (remember it is expressed at low rates)
the liver is the main site of branched-chain amino acid breakdown» we want this enzyme ON in the liver - so the OFF switch will be expressed at low rates here» its the off switch`
BCKDP – when it suffers a hypomrphic mutation
- similar symptoms to intermittent MSUD
- when the liver needs to turn on all of its inactive copies of BCDK, it can’t
what happens when inactive copies of BCDK can’t be turned on
leucine, isoleucine, valine and their keto-acids build up in the body, leading to a short period of MSUD symptoms
after a period of time with inactive BCKD
liver cells produce completely new BCDK trimers that aren’t off yet, patient returns to normal
BCKD phosphatase turns
BCKD on
BCKD kinase turns
BCKD on
when BCKDK suffers a hypomorphic mutation
opposite of MSUD
opposite of MSUD
instead of BCDK not working it works too much
result of opposite of MSUD
branched chain amino acids are broken down instead of being used to build proteins
big symptom of opposite of MSUD
cachexia
what is cachexia
“wasting away”
the loss of muscle mass and/or the failure to add new muscle mass
Intermittent MSUD
Like intermediate, trainer functions at 8-15% efficiency
Intermittent MSUD symptoms
Episodes rare, life can be normal w a proper diet. Episodes often accompany infections
