Nucleotide Metabolism Flashcards
What are the 3 basic principle components of nucleotides?
Nitrogenous base
Pentose Sugar
One or more phosphate groups
What are nitrogenous bases?
Heterocyclic ring compounds of nitrogen and carbon
What are the two types of nitrogenous bases?
Pyrimidines (1 ring) and Purines (2 rings)
What are the Pyrimidines?
Pyramids are CUT
Cytosine
Uracil
Thymine
What are the Purines?
Pure As Gold
Adenine
Guanine
What are the types of pentose sugars used in nucleotides?
Ribose and Deoxyribose
Where do nucleosides attach?
C-1 on sugar
N-9 on purine
N-1 on pyrimidine
What are nucleotides formed by?
Attachment of phosphate to sugar in nucleoside
Are phosphates ever attached to the base?
No never
How many phosphates are attached to sugars and at which sites on the sugar?
At least one phosphate is attached to C-2, C-3 or C-5 of the sugar
Can phosphates be added together?
Yes they can!
What are the deoxyribonucleotides?
Adenine
Guanine
Thymine
Cytosine
Name the two pathways for biosynthesis of nucleotides?
1) de novo (from new)
2) salvage
What is de novo biosynthesis?
Synthesis from metabolic precursors (Energy expensive)
What is salvage biosynthesis?
Recycle free bases and nucleosides released from nucleic acid breakdown (Energy economical)
What compound is a key substrate in both purine and pyrimidine de novo synthesis?
PRPP
What can IMP convert?
AMP or GMP
In purine synthesis what is the five membered ring built on first?
PRPP
What is the committed step of de novo purine biosynthesis?
Step 1: formation of 5-phosphoribosyl-1-amine
What inhibits the first step of de novo purine biosynthesis?
Asaserine, acivicin
What is required to make one molecule of insinuate from ribose-5-phosphate?
1 ATP for PRPP
2 ATP for 2N10-THF
4 ATP for 4 steps
SOOOOOO 7 ATP total
What do you watch for in the “wobble rules”?
Inosinate
What are the four mechanisms of de novo purine biosynthesis
1) Feedback inhibition of PRPP synthetase by end products
2) Feedback inhibition of committed step by end products
3) Feedback inhibition of branches by each end product
4) Reciprocal use of GTP & ATP in AMP, GMP pathways
What does the first step of pyrimidine biosynthesis and where does it occur?
This is the formation of carbamoyl phosphate which occurs in the cytoplasm (urea cycle in mitochondria)
What is the committed step of de novo pyrimidine biosynthesis?
Step 2: N-carbamoylaspartate which is catalyzed by aspartate transcarbamoylase
In humans are purine salvaged or do they go through de novo synthesis?
Purines are salvaged
What are XO inhibitors used for?
Treatment of gout
What is ADA (Adenosine deaminase deficiency) called?
SCID (Severe combined immunodeficiency)
What is SCID also known as?
Boy-in-the-bubble disease
Is there a cure for SCID?
No
What is ADA?
Rare heritable disease leading to one form of SCID (20% of all SCID cases)
What happens in SCID?
T and B lymphocytes do not develop properly
What is gout?
A probably heritable disease (mostly males) leading to elevated [uric acid] in blood and tissues.
What does excess urate lead to?
Precipitation of sodium rate in tissues which can become inflamed, painful and arthritic. Deposition in kidney tubules leads to damage.
What two mechanisms lead to elevated serum urate?
Hyperactive PRPP
Partial lack of HGPRT
What do you use to treat gout?
Allopurinol
Probenecid (up urate excretion)
Febuxostat (Uloric)
What is the first FDA approved medication to lower gout in over 40 years?
Febuxostat (Uloric)
For what individuals is Uloric good for?
Allergy to allopurinol
Kidney damage
What is Lesch-Nyhan Syndrome?
A very rare X-linked recessive disorder whose symptoms manifest by 2 years of age
What are the symptoms of Lesch-Nyhan Syndrome?
Mental retardation
Poor coordination
Extreme hostility and compulsive self-destructive tendencies (must be protected from themselves)
Gout
What is Lesch-Nyhan Syndrome caused by?
A complete lack of HGPRT which leads to brain damage.
