Purine and Pyramidines Flashcards
Immunodeficiency disorders is led by a mutation on which enzymes?
Deficiencies in purine nucleoside phosphorylase and adenosine deaminase lead to immunodeficiency disorders..
What leads to Lesch-Nyhan syndrome?
A deficiency in HGPRT (Hypoxanthine-guanine phosphoribosyltransferase). HGPRT mediates the conversion of Hypozanthine to IMP.
In this condition, purine bases cannot be salvaged. Instead, they are degraded, forming excessive amounts of uric acid.
What is the end product of purine ring degradation?
What happens when this accumulates?
The end product of purine degradation is Uric Acid, which is excreted in the urine.
Uric acid has limited solubility, and if it were to accumulate, uric acid crystals would precipitate in tissues of the body that have a reduced temperature (such as big toe / joints).
What drug reduces uric acid synthesis?
Allopurinol. This drug inhibits Xanthine oxidase (enzyme) therefore inhibiting the production of Xanthine which is a precursor of Uric acid.
What happens on the first committed step of purine synthesis and what enzyme catalyzes it?
PRPP reacts with glutamine to form 5-phosphoribosyl 1-amine. This rx produces nitrogen 9 of the purine ring, and its catalyze by Glutamine Phosphoribosyl amidotransferase.
How many ATP are needed to get to Inosine Monophosphate (IMP)
6 - ATP
Four key enzymes are regulated in Purine synthesis. Which enzymes are these, and what role do they play?
PRPP synthetase, amidophosphoribosyl transferase, adenylosuccinate synthetase, and IMP dehydrogenase. The first two enzymes regulate IMP synthesis; the last two regulate production of AMP and GMP respectively.
What inhibits the enzyme Glutamine Phosphoribosyl amidotransferase?
The end products of purine biosynthesis: GMP and AMP.
The enzyme is also inhibitted by the corresponding nucleoside diphosphates (ADP/GDP)) and triphosphates (GTP/ATP), but under cellular conditions, these compounds probably do not play a central role in regulation.
Where does most of the de novo synthesis of the bases of nucleotides occurs?
It occurs in the liver and to some extent in the brain, neutrophils, and other cells of the immune system.
What is the regulated step of pyrimidine synthesis?
What inhibits the enzyme?
The transformation of glutamine + CO2 + 2ATP to Carbamoyl Phosphate. The enzyme that catalyzed the rx CPS-II.
CPS-II is inhibited by UTP, hence low levels in cell will activate this, and it is activated by MAP kinase, which will phosphorylate the enzyme at a specific site.
What happens in Orotic Aciduria?
Which enzyme is affected?
In hereditary orotic aciduria, orotic acis is excreted in the urine because the enzymes that convert it to uridine monophosphate, ORATE PHOSPHORIBOSYLTRANSFERASE, are defective.
Pyrimidines cannot be synthesized and, therefore, normal growth does not occur. Oral administration of uridine is used to treat this condition.
What can happen if we have a deficiency of ornithine transcarbamoylase (enzyme)?
When orthinine transcarbamoylase is deficient (urea-cycle disorder), excess carbamoyl phosphate from the mitochondria leaks into the cytoplasm.
The elevated levels of cytoplasmic carboyl phosphate lead to pyrimidine production, as the regulated step of the pathway, the reaction catalyzed by carbamoyl phosphate synthetase II, is being bypassed. Thus, orotic aciduria results.
