Nitrogen Metabolism I and II Flashcards
nitrogen balance
in a normal human adult N(in) = N(out)
in a growing child, adolescent, pregnancy N(in) > N(out)
eating too little protein or lacking essential amino acids N(in) < N(out)
three sources for the amino acid pool
degradation of body proteins
dietary proteins
synthesis of non-essential amino acids
three fates of amino acids in the amino acid pool
synthesis of body proteins
precursors for essential nitrogen-containing small molecules
conversion to clucose, glycogen, fatty acids, or CO2
two main routes for amin removal
alanine aminotransferase transfers amino group from alanine to a-KG to make glutamate
aspartate aminotransferase transfers amino groups from glutamate to oxaloacetate to form aspartate
What coenzyme is required for aminotransferase reactions?
pyridoxal phosphate, a derivative of vitamin B6
What are the main sources for the nitrogen cycle?
What amino acid undergoes rapid oxidative deamination, and what is the enzyme that catalyzes this?
glutamate, glutamate dehydrogenase
uses NAD+ or NADP+ as the coenzyme
GTP is an allosteric inhibitor and ADP is an allosteric activator
What happens to D-amino acids from plants?
metabolized by D-amino acid oxidase in a FAD-dependent reaction in peroxisomes
Which amino acids do not undergo transamination reactions?
lysine, threonine, proline, and HO-proline
alanine aminotransferase reaction
aspartate aminotransferase reaction
glutamate dehydrogenase reaction
Describe the glucose/alanine cycle.
transfers nitrogen to the liver, ammonia in the blood is toxic so adds it onto alanine for transport
done primarily in muscle tissue
Describe the process of transporting nitrogen through blood as glutamine.
primarily used by peripheral tissues, but if there is a lot of tissue breakdown, muscle will use this process as well
Describe the oxidative deamination process by amino acid oxidases in peroxisomes.
Flavoprotein and FAD are the same
Describe the urea cycle.
Ornithine is an amino acid not used in proteins and is recycled
fumarate is a byproduct, connecting this with the TCA cycle
three mechanisms that regulate the urea cycle
substrate availability in a feed-forward mechanism
allosteric activation of carbamoyl phosphate synthease I (CPSI) by N-acetylglutamate (NAG)
induction/repression of urea cycle enzyme synthesis during high protein diet or during starvation
regulation of CPSI
main method of regulation, senses how much amine is coming in
How are the urea and TCA cycles linked?
Name and describe how the glucogenic amino aicds contribute to the TCA cycle.
carbons of these amino acids can be used in gluconeogenesis:
Thr, Gly, Trp, Ala, Ser, Cys, Asp, Asn, Tyr, Phe, Val, Ile, Met, Arg, His, Gln, Pro
Identify and describe how the ketogenic amino acids feed into the TCA.
ketogenic amino acids made acetyl CoA or acetoacetate:
Trp, Thr, Lys, Ile, Leu, Tyr, Phe
asparagine to oxaloacetate
a-KG from glutamine
a-KG from proline
type I hyperprolinemia - defect in proline dehydrogenase
typw II hyperprolinemia - defect in glutamate semialdehyde dehydrogenase
a-KG from arginine
hyperarginemia - defect in arginase
gyrate atrophy of the choroid and retina - mutations in ornithine-aminotransferase
a-KG from histidine
glutamate formimino transferase uses folate, so deficiency will cause high levels of Figlu
pyruvate from alanine
pyruvate from serine
pyruvate from cystine and cysteine
cystine is a dimer of cysteine
PAPS is used as a sulfate donor for the synthesis of sulfated proteoglycans
propionyl CoA from methionine and threonine
propionyl CoA can feed into the TCA cycle through conversion to succinyl CoA
S-adenosyl-L-methionine is important in single carbon transfer reactions
propionyl CoA by valine and isoleucine
oxidative decarboxylation by branched-chain alpha-keto acid dehydrogenase complex
deficincies in this enzyme result in maple syrup urine disease caused by accumulatiuon of branched-chain alpha-keto acids in theurine, giving it a sweet odor
occurs primarily in peripheral tissues and not liver
acetyl-CoA and acetoacetate from leucine
blockage of enzyme also causes maple syrup uring disease
also occurs primarily in peripheral tissues instead of liver
acetyl-CoA from tryptophan
first step of the process requires vitamin B6
fumarate, acetyl CoA and acetate from tyrosine
type II tyrosinemia, neonatal tyrosinemia, alkaptonuria, type I tyrosinemia
lysine degradation
produces a dicarboxylic acid which can undergo beta-oxidation
synthesis of non-essential amino acids
asparagine, aspartate, glycine, serine, cysteine, alanine, glutamate, glutamine, proline, arginine
serine from glycolysis intermediates
glycine from serine
folate as cofactor
major reaction is serine to glycine
cysteine from serine and methionine
proline from glutamate
glutamate semialdehyde dehydrogense is important
synthesis and degradation of spartate and asparagine
tyrosine from phenylalanine
phenylketonuria is a disease due to deficiency in phenylalanine hydroxylase
leads to alternative pathways which give urine particular odor
nucleoside
base with sugar
nucleotide
phosphorylated nucleoside
purine biosynthesis frome ribose 5-phosphate
requires folic acid
first reaction is important
R5P comes from PPP
end result is inosine monophosphate
AMP and GMP from IMP
Describe the regulation of de novo purine nucleotide biosynthesis.
AMP, GMP, ADP, and GDP all regulate the intial steps of purine biosynthesis
Describe the regulation involved in balancing ATP and GTP levels
salvage of purine bases
Lesch-Nyhan syndrome - complete deficiency of HGPRT, unable to salvage hypoxanthine or guanine leads to productio of excess uric acid
HGPRT = hypoxanthine-guanine phosphoribosyl transferase
biosynthesis of pyrimidines
starts from glutamine and CO2, ends up as UDP, which can be converted into TMP or CTP
folate is a carbon donor
interregulation of nucleotides
synthesis of deoxyribonucleotides
maintains a blance of deoxyribonucleotides for DNA synthesis
high ATP levels can cause problems if not regulated such as in immunodeficiency disease as the result of an adenine deaminase deficiency
degradation of purines
occurs in cells of intestinal mucosal cells of the small intestine with uric acid as the final product
gout - caused by high levels of uric acid in the blood, resulting in the deposition of monosodium urate in the joints
allopurinol can be used to treat by decreasing rate of degradation
degradation of pyrimidines
eventually converted to succinyl CoA
tetrahydrofolate (FH4)
the main coenzyme in accepting one carbon groups, once one-carbon groups reduced to methyl, carbon cannot be re-oxidized
have to get folate from diet
sources of one-carbon groups
serine, glycine, formaldehyde, histidine, formate
dTMP from dUMP
transfer of a one-carbon unit, uses TH4
cancer treatment dugs 5-fluorocuracil and methotrexate interfere with this pathway to kill dividing cells
viatmin B12 (cobalamin
involved in transfer of methyl group to homocysteine to form methionine
also involved in rearrangement of L-methylmalonyl CoA to form succinyl CoA
S-adenosylmethionine (SAM) from methionine
SAM is a major methyl donor for formation of methylated histones
methionine obtained from diet or produced from homocysteine
The Methyl-Trap Hypothesis
vitamin B12 is required to take methyl group from FH4, if deficient for vitamin B12 or if methionine synthase is defective, the N5-methyl-Fh4 will accumulate and most of the folate in the body becomes trapped there, creating a functional folate deficiency
