Amino Acid catabolism and urea production Flashcards
when does amino acids catabolism occur?
- Normal protein degradation and synthesis inside the cell
2.Carnivore animals - Excess of amino acids in diet
- Starvation and uncontrolled diabetes
Main steps of digestion of proteins
Enzymes
Gastrin stimulates secretion of ___ by parietal cells and secretion of ___ by chief cells
HCl, pepsinogen (zymogen)
pepsinogen self-cleaves at __ pH to generate active pepsin
low
___ cuts protein into peptides in the stomach
pepsin
___ and ___ cut proteins and larger peptides into smaller peptides in the small intestine
trypsin, chymotrypsin
____ and ________ in the small intestine degrade peptides into amino acids which are absorbed
aminopeptidase, carboxypeptidases A and B
1st step of amino acid catabolism
amino acid is converted to NH4+ and a-keto acids
Glutamate (Glu) and Glutamine(Gln) is converted to
a-ketoglutarate
Alanine (Ala) is converted to
pyruvate
Aspartate (Asp) is converted to
oxaloacetate
nitrogen metabolism is played by what amino acids?
Alanine,Aspartate,Glutamate,Glutamine
T/F Many aquatic vertebrates release ammonia to their environment through passive diffusion from epithelial cells and active transport via gills
T
Plants conserve ___
nitrogen
Many terrestrial vertebrates and sharks excrete nitrogen in the form of __
urea
why many terrestrial vertebrates and sharks excrete nitrogen in the form of Urea?
- it is less toxic than ammonia
- it has a high solubility in water
Birds and reptiles excrete nitrogen as _____
uric acid
why birds and reptiles excrete uric acid?
it is insoluble (excretion as “paste” allows the animals to conserve water
Humans and great apes excrete both __ (from amino acids) and __ (purines)
urea, uric acid
step 1: removal of the amino group
free ammonia is captured by a series of transamination reactions and transamination allow transfer of an amine to a metabolite (e.g. a-ketoglutarate) and generate glutamate
enzymatic transamination is catalyzed by ____
aminotransferases
what cofactor enzymatic transamination uses ?
pyridoxal phosphate cofactor (PLP, vitamin B6)
what molecule accepts amino groups, generating L- glutamate?
a-ketoglutarate
what molecule acts as a temporary storage of nitrogen?
L-glutamate
___ can donate back the amino group when needed for amino acid biosynthesis
L-glutamate
elevated levels of ALT and AST indicate ….
liver dysfunctions (cirrhosis, hepatitis)
what enzymes are measured in the serum to assess liver function?
Alanine transaminase (ALT) and aspartate transaminase (AST)
excess ammonia is transported to the liver and even lower extent of the kidneys via ___ to be transformed into urea
glutamine
Oxidative deamination occurs when ….
ammonia collected in glutamate is further removed by glutamate dehydrogenase in mitochondria matrix
Oxidative deamination use __ as electron acceptor
NAD+ and NADP+
Ammonia is processed into __ for excretion
urea
pathway for ammonia excretion is called …
transdemamination
transdemamination consists of
transamination and oxidative deamination
BUN
blood urea nitrogen
BUN measures ___
total nitrogen
Azotemia
Excess of nitrogenous
waste products in the
blood (high BUN); uremia usually due
to kidney failure
If NH4+ can’t permeate through the membrane, what molecule can?
NH3 (since it is neutral)
Brain is very sensitive to what molecule?
NH3
what makes the brain sensitive to NH3?
excess NH3 is converted to glutamate (excitatory neurotransmitter) via glutamate dehydrogenase
In the case of liver failure, excess glutamate builds up in neurons and some it is converted to GABA (inhibitory neurotransmitter, modulates muscle tone) and can cause Asterixis (flapping tremor, liver flap) and coma
Asterixis (liver flap) is directly related to high concentrations of ___ in the brain
glutamate
treatment of asterixis
administration of lactulose
Urea cycle (mnemonic: come on sally lets act)
- ammonium is converted to carbamoyl via CPS1
- carbamoyl PO4 and Ornithine is converted to citrulline via OTC
- aspartate and citrulline is converted to argininosuccinate via synthetase
- argininosuccinate is converted to arginine and fumarate via lyase
- arginine is converted to urea and ornithine via arginase
Essential or non essential: amino acids must be obtained as dietary protein
essential
Essential or non essential: amino acids easily made from central metabolites
non essential
9 essential amino acids ( harry is loving lauren miller pink thong that vibrate)
histidine
isoleucine
leucine
lysine
methionine
phenylalanine
threonine
tryptophan
valine
5 non essential AA (mnemonic: triple A Sexy Girl)
alanine
asparagine
aspartate
glutamate
serine
5 essential AA that are both glucogenic and ketogenic (mnemonic: triple T P.I)
isoleucine
phenylalanine
tryptophan
threonine
tyrosine
2 essential AA that are ketogenic ONLY (2 Ls)
leucine
lysine
which substance is NOT involved in the production of urea from NH4+ via the urea cycle?
Acetyl CoA
In AA catabolism, the 1st rxn for many AA is:
transamination requiring PLP
which enzyme can access liver function
alanine transaminase
in muscles, pyruvate is combined with glutamate to yield alpha ketoglutarate and ____
alanine
how many ATP are used to generate one molecule of urea within urea cycle?
4
urea contains 2 nitrogen atoms. one nitrogen comes from ammonia while the other comes from _________
aspartate
N-acetylglutamate acts as an allosteric activator of _____
CPS1
in the urea cycle, arginase catalyzes …
formation of urea from arginine
cofactors in AA catabolism
biotin
SAM
folic acid
plp or vitamin b6
sulfonamide antibiotics are PABA analogs and acts as competitive inhibitors of ….
dihydropteroate synthase and bacterial folic acid synthesis
folate is a vitamin …
B9
Bactrim consists
sulfamethoxazole and trimethoprim
sulfamethoxazole does what?
inhibit folate synthesis
trimethoprim does what?
inhibit bacterial dihydrofolate reductase 50,000x more than human enzyme
symptoms of PKU
Heart problems, microcephaly, low birth weight, intellectual
disabilities, mental disorders, seizures, newborns genotyped at birth for PAH mutations
treatment of PKU
- reduce Phe in diet
- synthetic BH4 ( Sapropterin)
