Nucleotide Metabolism Flashcards
Nucleoside
Nitrogen-containing ring compounds linked to a 5-carbon sugar (ribose/deoxyribose)
Nucleotide
A nucleotide consists of a nitrogen-containing
base, a five-carbon sugar, and one or more
phosphate groups. (Nucleoside + P)
Purine base
five-membered ring fused to the six-membered ring
(Guanine & Adenine)
Pyrimidine Base
Six-membered ring
Cytosine (C), thymine (T), and uracil (U)
RNA
- Single stranded
- OH on 2’ position of the ribose carbon ring
- A,G,C,U
- more transient carrier of molecular instructions
DNA
- H on 2’ position of the ribose carbon ring
- A,G,C,T
- double stranded ( held together by H bonds)
- Long term repository for heredity information
Nucleotide Functions
- They carry chemical energy in their easily hydrolyzed phosphoanhydride bonds.
- They combine with other groups to form coenzymes.
- They are used as small intracellular signaling molecules in the cell.
What molecule is PRPP derived from, and what pathway generates this molecule?
- PRPP is derived from the ribose-5 phosphate that is generated by the pentose phosphate pathway.
What purine is made first by the de novo pathway for purine synthesis?
- The purine inosine monophosphate (IMP) is formed first, it is then converted to either adenosine monophosphate (AMP) or guanosine monophosphate (GMP)
What enzyme is needed for synthesis of GMP by the purine salvage pathway?
enzyme HGPRT is needed for GTP synthesis
What enzyme is required for de novo synthesis of purines?
amido PRT, this enzyme catalyzes the conversion of PRPP and glutamine to purine nucleotides.
What pyrimidine is formed first in the pyrimdine de novo synthesis pathway
orotate monophosphate (OMP) is the first pyrimidine based formed
Is PRPP needed for pyrimidine synthesis?
Yes
What are the 2 products of the first step of degradation of purines?
hypoxanthine and xanthine
What is the end product of purine degradation?
Uric Acid
What is the end product of uracil degradation?
acetyl CoA
What is the end product of thymidine degradation?
Succinyl CoA
Roles of ribonucleotides :
- building blocks for RNA
- ATP
- intracellular signaling molecules (cAMP)
Degradation of purine generates ____
Uric Acid
catalyzed by ribonucletide reductase ( this is a drug target)
UMP, AMP, GMP, CMP ribonuc. ——> Deoxyribonuc.
Thymidylate synthase
- catalyzed the conversion of TMP is generated from UMP
- This conversion requires THF
Dihydrofolate Reductase
- is a Drug Target
- Required for synthesis of THF
- inhibition will leat to dTMP cannot be made
Degradation of pyrimidine nucleotides generates ____
intermediates that can be further metabolized and enter the TCA cycle
Pyrimidine metabolism
De novo synthesis
- Orotate is the first base formed
- Orotate is then joined to PRPP to form orotate monophosphate (OMP)
- OMP is then used to synthesize all other pyrimidine nucleotides
Pyrimidine metabolism
Salvage;
- Uracil or orotate (pyrimidine bases) + PRPP = pyrimidine nucleoside monophosphate (i.e. UMP or CMP)
- catalyzed by UPRT and OPRT
- end product is acetyl coA and succinyl coA
Elimination of uric acid from the body
• Uric acid is eliminated by the kidney (65%)
and via the GI tract (35%)
• Approximately 90% of filtered uric acid is
reabsorbed via urate transporter 1 (URAT1)
• URAT1 polymorphisms may predispose
patients to gout (= increased uric acid
reabsorption = increased uric acid plasma
levels)
HGPRT
an enzyme that is associated with the purine salvage pathways – it is needed to generate GMP and IMP (guanine and hypoxanthine are substrates, respectively)
APRT
enzyme that is associated with the purine salvage pathway – it is needed to generate AMP (substrate is adenine)
Decreased activity of the salvage pathway leads to ____
increased activity of the de novo pathway
Genetic deficiencies of HGPRT (salvage pathway enzyme)
- eventually leads to increased in uric acid –> hyperucemia
- purine bases are not salvaged and are degraded to uric acid… = increased uric acid levels (also, decreased activity of the purine salvage pathway causes increased activity of the purine de novo pathway)
Excess of PRPP
increases purine de novo pathway
because PRPP activates amido PRT
Purine metabolism;
De novo synthesis
the first purine nucleotide made via de novo synthesis is IMP. IMP can then be converted to all other purine nucleotidesamido PRT is a regulated enzyme
Purine Salvage pathway;
Hypoxanthine + PRPP⇒ IMP + Ppi, catalyzed by HGPRT
Guanine + PRPP ⇒ GMP + Ppi, catalyzed by HGPRT
Adenine + PRPP ⇒ AMP + Ppi, catalyzed by APRT
Amido PRT
(amido phosphoribosyltransferase) is the regulated step for IMP synthesis; it is positively regulated by PRPP and negatively regulated by purine nucleotides
