Purine and Pyrimidine Metabolism Flashcards
(39 cards)
Maybe know the structures of the amino acids
Actually yeah know them
Guanine and Adenine are purines. Adenine has an amine on carbon 6. Guanine has a ketone on carbon 6 (and an amine on carbon 2). The other ring is five carbons (three more).
Cytosine, Uracil, and Thymine are pyrimidines. Uracil has two ketones in the carbon 2 and 4 places. Cytosine has a ketone at carbon 2 and an amine at carbon 4. Thymine is basically uracil (ketone at carbons 2 and 4) with a methyl group at carbon 5.
Difference between deoxyribose and ribose
ribose has OH group at 2’ carbon
Starting material for purines
ribose-5-phosphate (build on the purine base)
Glycine, 2 Glutamine amides, and an aspartate amino combined with bicarbonate, and two C1-H4folate. Requires 6 ATP and 5-phosphoribosyl-1-pyrophosphate (PRPP)
Starting material for pyrimidine
synthesize pyrimidine ring and then attache the ribose-5-phosphate
Rate-limiting step of purine synthesis
Glutamine:phosphoribosyl amidotransferase (or amido phosphoribosyl transferase) Converts PRPP (5-phosphoribosyl-1-pyrophosphate), water, and glutamine into Glutamate, pyrophosphate, and 4-phosphoribosyl 1-amine
What is required for de novo synthesis of a purine?
Glutamine and PRPP become 5’-phosphoribosylamine
ATP and Glycine
Formyl-THF
ATP and Glutamine
ATP
CO2
ATP and Aspartate
Formyl-THF
(So 4 ATP, 2 Formyl-THF, Glycine, Glutamine, Aspartate, and CO2 forms IMP)
Then GTP and Aspartate is used to make AMP
and ATP and Glutamine is used to make GMP
What regulates purine nucleotide synthesis?
PRPP synthetase is inhibited by ADP and GDP
Glutamine phosphoribosyl amido transferase is inhibited by GMP and AMP
IMP dehydrogenase is inhibited by GMP
Adenylosuccinate synthetase is inhibited by AMP
True or false: De novo synthesis requires less ATP than the salvage pathway.
False
Describe the salvage pathway for purine synthesis
There are two pathways
There is a hypoxanthine-guanine phosphoribosyl transferase pathway (HGPRTase)
(It uses hypoxanthine or guanine and PRPP (5-phosphoribosyl-1-pyrophosphate)
(Makes GMP or IMP and pyrophosphate)
The other pathway uses adenine phosphoribosyltransferase (APRTase), which uses adenine and PRPP to make AMP and pyrophosphate
Defective protein in Lesch-Nyhan disease?
HGPRT (Hypoxanthine-guanine phosphoribosyl transferase) (Complete lack of protein)
Deficiency of adenosine deaminase can cause?
SCID (Severe combined immunodeficiency)
(No B or T cells)
Causes accumulation of dATP in lymphocytes, which inhibits ribonucleotide reductase
Deficiency of purine nucleoside causes?
Lack of T cells
(No degradation of inosines and guanosines to free bases)
(Nucleosides accumulate)
What would you see an increase of in those with Lesch-Nyhan disease?
Xanthine and Uric acid (the end product of hypoxanthine and guanine)
Regulation of Purine salvage pathway
HGRPTase inhibited by IMP and GMP. APRTase inhibited by AMP
AMP and GMP also inhibits de novo synthesis pathway. The use of PRPP also reduces de novo synthesis pathway.
What disease is related to lack of HGPRTase?
Lesch-Nyhan disease
Description of entirety of Lesch-Nyhan disease
Complete lack of HGPRT
X-linked (males affected)
No salvage pathway, increased uric acid, greater de novo purine synthesis
Severe neurological disease and urate nephrolithiasis (kidney damage)
Hyperuricemia
Left untreated, death in first decade. Treated with allopurinol (competitive inhibitor of xanthine oxidase) (allopurinol prevents nephropathy but does not affect neurological or behavior symptoms)
What does allopurinol do?
Inhibits xanthine oxidase, results in buildup up hypoxanthine and xanthine
In de novo pyrimidine synthesis, the carbons and nitrogens come from?
The carbons ( and one nitrogen) come from aspartate and the other nitrogen comes from glutamine amide. One other carbon comes from bicarbonate ion.
Pyrimidine synthesis process
nitrogenous base assembled, then sugar and phosphate added. Nitrogenous base comes from aspartate, glutamine, and bicarbonate ion
carbamoyl phosphate synthetase takes glutamine, carbon dioxide, and two ATP to create 2 ADP, glutamate, phosphate, and carbamoyl phosphate. That is converted to N-carbamoyl aspartate, then hihydroorotate, orotate, and then OMP (Orotidine 5’-mono-phosphate). Orotidine 5’-mono-phosphate decarboxylase converts it to UMP, which is converted to UTP and then CTP.
Stuff to know about carbamoyl phosphate synthetase
CPSII is cytoplasmic. It uses nitrogen from glutamine. It is activated by PRPP (5-phosphoribosyl-1-pyrophosphate). It is inhibited by UTP
(CPSI is in mitochondria and uses ammonia as a an amino acid source)
Hereditary orotic aciduria
results from deficiency in orotate phosphoribosyl transferase or OMP decarboxylase. Treated with uridine (nucleoside, because de novo synthesis not possible).
What makes NDPs?
nucleoside monophosphate kinases (adenylate kinase or guanylate kinase
What protein makes NTPs?
nucleoside diphosphate kinase
True or false: Ribonucleotides are precursors of deoxyribonucleotides.
True
