TOPIC A/2: Nitrogen metabolism Flashcards
Which bases are purines
adenine and guanine
What bases are pyrimidines
thymine, cytosine and uracil
What are the 2 pathways of nucleotide synthesis
De Novo pathway
Salvage pathway
Where does nucleotide synthesis occur
predominantly in the liver
outline the de novo pathway
Starts with a precursor such as
amino acids
ribose 5-phosphate
CO2 and NH3
Builds nucleotide form basic molecules
why are nucleotides important in a cell
make up DNA/RNA
energy carriers (e.g. ATP)
Components of cofactors and activated intermediates
Signalling molecules (e.g. cAMP)
Outline the salvage pathway
Starts with bases available through degradation of other nucleic acids
recycles bases
Outline purine build up
PRPP to IMP then GMP and AMP
GMP and AMP inhibit enzymes acting on IMP
Outline purine break down
produces uric acid
salvage pathway can produce GMP form guanine or iMP form hypoxanthine
Outline gout
Defective enzymes of purine degradation
high uric acid and arthritis
Outline severe combine immunodeficiency (SCID)
Adeonsine deaminase deficiency
dATP not converted to inosine. inhibits ribnucleotide reductase
no dNTP produced, DNA cannot be made
T and B cells with high DNA synthesis cannot replicate properly causing immune deficiency
treatment, repeated gene therapy
Outline Lesch-Nyan syndrome
HGPRT deficiency blocks salvage pathway
no recycling of bases, high uric acid waste
Only De Novo
malfunction of CNS
Outline pyrimidine build up
PRPP + orotate = UMP then to UTP and CTP
CTP inhibits first reaction
Outline pyrimidine break down
broken down to malonyl-CoA and nitrogen converted to urea
cytidine, uridine and deoxythymidine can all be converted back to nucleotide form
Outline hereditary orotic aciduria
enzyme deficiency in UMP synthesis
severe anaemia, growth retardation, high orotic acid excretion
treatment, feeding uridine
Explain why Drugs can target pyrimidine metabolism
ribonucleotide reductase converts ribose to deoxyribose forms
thymidylate synthase catalsyses dUMP to dTMP, folate is required
targeting this can help stop cells that replicate to quickly (cancer)
Name the drugs targeting thymidylate synthase reaction
(chemot)
Fluorouracil: inhibits thymidylate synthase
(chemot) Methotrexate and Aminopetrin: prevent folate regeneration
(antib)
Trimethoprim: prevent folate regeneration
Outline transamination
transfer of amino group from amino acid to a keto acid
catalysed by transaminase (aminotransferases)
ends with alpha keto acid
mostly occurring in liver
outline deamination
cleavage of amino group from glutamate
ends with alpha ketoglutarate and ammonium
catalysed by glutamate dehydrogenase
how do amino acids travel to the liver
glutamine-glutamate cycle
outline the glutamine-glutamate cycle
deamination forms glutamate
glutamine transports NH3 to liver for excretion
how do amino acids travel to the liver FROM MUSCLE
glucose-alanine cycle
outline the glucose-alanine cycle
muscles breakdown amino acids for energy during starvation
NH3 travels as alanine to liver from muscle
deaminated to pyruvate which can be converted to glucose for energy
Energy requirement of urea cycle
4 phosphates per urea
