Unit 7 Flashcards
DNA and RNA purines
Adenine
Guanine
RNA pyrimidines
Cytosine
Uracil
DNA pyrimidines
Thymine
Cytosine
Difference between purines and pyrimidines
Purines have 2 rings
Pyrimidines have only 1
Nucleosides end will end in
-one
Nucleotides will end in:
-late
What can synthesize nucleotides in the de novo pathway?
Amino acids
Ribose-5-phosphate,
CO2
NH3
In the salvage pathway, nucleotides can be salvages from _______ released from the breakdown of:
Nucleobases
Nucleic acids
Compounds that inhibit ______ pathways are promising anti-parasite drugs
Salvage
In purine de novo biosynthesis, bases are synthesized while attached to:
Ribose
In pyrimidine de novo biosynthesis, only (BEFORE/AFTER) complete synthesis of bases, they are attached to what?
Before
Activated sugar 5-phosphoribosyl-1-pyrophosphate (PRPP)
Site of purine synthesis
Liver
Amino acids in purine ring
Glycine
Aspartate
Glutamine
Major contributors of purine ring
Amino acids
CO2
N10- formyl THFf
End products of de novo purine biosynthesis
Ribonucleotides
Activator or PRPP synthetase
Pi
Inhibitors of PRPP synthetase
Purine
Ribonucleotides
De novo biosynthesis of purines begins with:
PRPP with glutamine
During de novo biosynthesis of purines, what are synthesized as AMP and GMP?
Adenine and guanine
In de novo biosynthesis of purines, the ring builds up following the addition of:
3 atoms from glycine
What is the first intermediate with a full purine ring?
Inosin monophosphate (IMP) or inosinate
Intermediate needed for Inosinate to adenylosuccinate
Adenylosuccinate synthetase
What enzymes are needed for IMP - adenylosuccinate
Aspartate and GTP
Intermediate for IMP to XMP (xanthylate)
IMP dehydrogenase
Enzymes needed for IMP- XMP
H2O,
NAD+
To make GMP, inosinate is deoxidized to _______,
This then takes on intermediate ________, with enzymes ___ and ______ to GMP
Xanthylate
XMP-glutamamine aminotransferase
Glen
ATP
Site of nucleic acid degradation
Gut
In the stomach, what denatures nucleic acid?
Low pH
What hydrolysis nucleic acids to nucleotides?
Pancreatic nucleases
Intestinal mucosal cells derived nucleotides ________ nucleotides to nucleosides
Dephosphorylate
______ nucleosidases generate nitrogenous bases
Intestinal
Review slide 10 picture
Slide 10
Autosomal recessive deficiency that causes a type o f severe combined immunodeficiency (SCID), involving T cell, B cell and natural killer-cell depletion (lymphocytopenia)
Adenosine Deaminase (ADA) deficiency
In catabolism of purine, adenosine is deaminated to _______
Then hydrolysis to:
Inosine
Hypoxanthine and xanthine
In catabolism of purine, guanosine yields ______ via:
Xanthine
Hydrolysis and deamination
In catabolism of purine, xanthine is oxidized into ______ by:
Uric acid
Xanthine oxidase
What is a cofactor for xanthine oxidase?
Molybdenum
Rare autosomal recessive deficiency that only affects T cells .
Purine nucleoside phosphorylase (PNP) deficiency
Problems PNP deficient people have
Recurrent infections and neurodevelopment delay
Disorder characterized by uricemia with recurrent attacks of acute arthritic joint inflammation, caused by deposition of mono-sodium irate crystals
Gout
In gout, the hyperuricemia results primarily from :
The underexcretion of uric acid
Treatment with ______ inhibits xanthine oxidase, resulting in an accumulation of:
Allopurinol
Hypoxanthine and xanthine (compounds more soluble that uric acid)
What is important for both salvage and de novo synthesis
PRPP
What is reused in salvage pathways for purines?
Free bases released in metabolism
Adenine reacts with PRPP to form:
It is catalyzed by:
Adenine nucleotide AMP
Adenine phosphoribosyltransferase
Organ especially dependent on salvage pathway
Brain
Lack of hypoxanthine-guanine phosphoribosyltransferase leads to:
Lesch-Nyhan syndrome
Syndrome that causes neurological impairment, and finger and toe biting behavior
Lesch-Nyhan syndrome
Catalyst for hypoxanthine -> IMP
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Catalyst for guanine to GMP
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
CPS I
Cellular location:
Pathway involved:
Source of nitrogen:
Regulators:
Mitochondria
Urea cycle
Ammonia
Activator: N-acetyl-glutamate
CPS II
Cellular location:
Pathway involved:
Source of nitrogen:
Regulators:
Cytosol
Pyrimidine synthesis (de novo)
Gamma-amide group of glutamine
Activator: PRPP
Inhibitor: UTP
What is the first full ring synthesized in de novo biosynthesis of pyrimidines?
Dihydroorotate
Intermediate for Orotate -> Crotidine 5’monophosphate
Orotate phosphotibosyl transferase
Also takes in PRPP here
Intermediate for Crotidine 5’-monophosphate ->.Uridine 5’-monophosphate
OMP decorboxylase
First Nucleotide formed in de novo biosynthesis of pyrimidines
Uridine 5’-monophosphate
Low activity of Orotate phosphoribosyltransferase and/or OMP decarboxylase could result in:
Poor growth,
Megoblastic anemia
Excretion of large amounts of Orotate in the urine
What helps improve anemia and decreased excretion of Orotate?
Administration of uridine
Ribonucleotides are precursors to:
Deoxyribonucleotides
Activated state of ribonucleotide reductase is:
Deoxidized, with sulfa-hydro containing enzymes
What enzymes are needed to oxidize ribonucleotide reductase?
What do they do?
Glutaredoxin or thioredoxin
Two H atoms are donated by NADPH and Carried by these two.
Activator at primary regulatory sites for regulation of ribonucleotides
Inhibitor:
ATP
dATP
Activator of substrate specificity for regulation of ribonucleotides
DATP,
Binding of substrates will activate one another
Deamniation of ___ or phosphorylation of ____ yields dUTP
DCTP
dUDP
Dephosphorylation of _____ by _____ yields dUMP
DUPT
DUTPase
Methylation of dUMP by ______ ______ yields ___
Thymidylate synthase
DTMP
What is a target for anti cancer drugs?
Thymidylate synthase
DTMP is found exclusively found where?
In DNA
DUDP -> dUTP needs what ?
Nucleoside diphosphate kinase
DUMP -> DTMP need what?
Thymidylate synthase
Cancer drugs will block ________ and/or ______
N5,N10-methylene-tetrahydrofolate
7,8 dihydrofolate
_______ and _______ are important chemotherapeutic agents
Fluorouracil
Methotrexate
In cells, fleorouracil is converted to _____, which inhibits _____ ____
FDUMP
Thymidylate synthase
Methotrexate, a structural analog of ______, inhibits _____ ____
Tetrahydrofolate
Dihydrofolate reductase
Widespread deficiency in nutritionally poor populations
Folic acid deficiency
Folic acid deficiency leads to:
Reduced Thymidylate synthesis
Reduced Thymidylate synthesis causes:
Uracil to be incorporated into DNA
In catabolism and salvage of pyrimidines, the ring is:
Open
Catabolism and salvage of pyrimidines-
CMP and UMP degrade to:
TMP degrades to:
Final end products:
Beta-alanine
Beta-aminosobutyrate
NH3/Urea and CO2
Painful joints (often in toes) due to deposits of sodium urate crystals
Gout
Does gout primarily effect males or females?
Males
Gout may involve genetic under-excretion of ______, and/or over-consumption of _____
Urate
Fructose
How is gout treated?
With avoidance of purine-rich foods (seafood, liver)
Or avoidance of fructose
Or with xanthine oxidase inhibitor allopurinol
Allopurinal can also be used to treat:
Why?
Sleeping sickness (trypanosomiasis)
Trypanosomes lack enzymes for de novo nucleotide synthesis
Trimethoprim can inhibit _____ ____ ____, but binds:
Bacterial Dihydrofolate
Human enzyme several orders of magnitude less strongly
Principle electron reduction for ribonucleotide reductase
NADPH