Nitrogen Metabolism Flashcards
Nitrogen Metabolism-Amino Acids, Purines, Pyrimidines and Products Derived from Amino Acids. Pyrimidine and Purine Synthesis and Metabolism
The first committed and regulated step of purine biosynthesis
synthesis of phosphoribosylamine
Transports the bases and nucleosides to other tissue from liver
RBC
starting materials for purine breakdown
AMP and GMPAMP–> Adenosine –> inosine –> hypoxanthine –> xanthineAMP–> IMP–> inosine –>hypoxanthine –> xanthineGMP –> Guanosine –> Guanine –> xanthine
5 different precursors for purine synthesis
AspartateGlutamine (amide N) X2N10-Formyl-FH4 X2GlycineCo2
the amino group of adenine is from
Asp
dihydropyrimidine dehydrogenase
T+NADPH –> dihydroT + NADP
The two end product of the last steps of pyrimidine breakdown, Which can be used in TCA cycle
succinyl Co-A and Acetyl Co-AFormer from B-aminoisobutyrate and latter from B-alanine
The byproduct of IMP dehydrogenase
NADH + H+
the first reaction of pyrimidine breakdown starting from U
C —-> NH4+ + U (deamination)
the precursor for acetyl-coa and succinyl coa in pyrimidine breakdown
(U)B-alanine –>Acetyl Co-A
(T) B-aminoisobutyrate –> succinyl Co-A
The enzyme that catalyzes the following reaction:Adenylosuccinate –> fumarate + AMP
Adenylosuccinase
XMP
xanthosine monophosphate
adenylosuccinate synthetase catalyzes this reaction
Asp + IMP –> adenylosuccinate
Asp + IMP –> adenylosuccinate
is catalyzed by …….
Hint: the first step of AMP synthesis and requires GTP
adenylosuccinate synthetase
Most of the de novo synthesis of purine takes place in
liver
Are the sources of metabolic energy and precursors for RNA synthesis
ATP and GTP
Starting materials for pyrimidine breakdown
C, T
The products of purine breakdown
uric acid with low plasma solubility
Name all the four enzymes for the formation of AMP and GMP from IMP
adenylosuccinate synthetase
adenylosuccinase
IMP dehydrogenase
GMP synthase
The purpose and the requirements of reciprocal regulation
requires GTP and ATP
The purpose is to maintain balance between the synthesis of AMP and GMP:
1- AMP neg. feed back on adenylosuccinate synthetase AND
2- GMP neg. feedback on IMP dehydrogenase
The main source of ribose-5-phosphate
pentose phosphate pathway
The last step common for purine breakdown regardless of starting material
xanthine –> uric acid (Catalyzed by xanthine oxidase)
the first purine nucleotide
IMP- inosine monophosphate
Formation of dihydrothymine and dihydrouracil
rate determining steprequires NADPHEnzyme : dihydropyrimidine dehydrogenase
The enzyme, reactant, products and starting reactions of purine salvage pathway
startting- Guanine / hypoxanthineGuanine + PRPP –> GMPHypoxanthine +PRPP–> IMPThe enzyme that catalyzes both reactions is HGPRT
an inhibitor of xanthine oxidase
allopurinol
Due to the high energy expense, this pathway converts free bases and nucleosides to nucleotides
Salvage pathway
the enzyme that catalyzes the first committed step of purine biosynthesis
GPAglutamine phosphoribosyl amidotransferase
HGPRT defeciency
HGPRT converts Hypoxanthine and guanine to IMP and GMP respectively.It also requires PRPP. Therefore, deficiency leads toinc uric acid as a result of dec in HGPRTand dec in PRPP and ultimately inc uric acid productionoften seen in lesch-Nyhan syndrome
The energy requirement for one purine synthesis
~ 6ATP
The first step of GMP production from IMP
E: IMP dehydrogenasehypoxanthine base is oxidized by IMPdehydrogenase to xanthine- Specifically XMP
Three steps for regulation of purine synthesis
1- committed step - GPA inhib by end products2- second level- PRPP synthetase (also used in salvage pathway)3- reciprocal regulation- maintains balance between the synthesis of AMP and GMP
donates nitrogen to XMP to form GMP
glutaminesecond step of GMP production from IMP
Two step production of AMPindicate the step that requires energy
1- Asp + IMP –> adenylosuccinate* It requires energy from GTP2- adenylosuccinate –> fumarate + AMP
Purine synthesis begins with
Attachment of amino group from Gln to ribose moiety.
HGPRT
hypoxanthine-guanine Phosphoribosyl transferase
Fumarate is released from this molecule to form AMP- Adenosine MonoPhosphate.
Adenylsuccinate
The amino group of guanine is from
Gln
The by products of Acetyl-CoA and Succinyl CoA synthesis in pyrimidine breakdown
Ammonia (used in urea cycle) and Co2
The enzyme that catalyzes Guanine –> Xanthine +NH4+
Guanase.GMP–> Guanosine –> guanine –> xzanthine —> uric acid
phsophorylate AMP and GMP
nucleoside monophosphate kinase
Adenosine –?-? inosine –> hypoxanthinepurine breakdown- starting from AMP
ADAAdenosine deaminaseNH4+ forms
The two enzymes for the production of GMP from IMP
1- IMP dehydrogenase 2-GMP synthetase
The rate limiting step of pyrimidine breakdown
formation of dihydroT and dihydroU
pathway for uric acid conversion to urine (general-schematic)
uric acid –> blood –> sodium urate –> kidney –> urine
The enzyme(s) for the following reactions:
hypoxanthine —> xanthine —> uric acid
(Both release H2O2)
Xanthine oxidase
the step of GMP production that requires energy and the associated enxyme
GMP synthaseRequires energy from ATP
phosphorylates and forms ATP and GTP
nucleoside diphosphate kinase
The base of the first purine nucleotide
the base of IMP is hypoxanthine
the result of allopurinol
allopurinol is xanthine oxidase inhibitor.Xanthine oxidase catalyzes the following reactions:hypoxanthine –> xanthine –> uric acid(a series of oxidation reaction and H2O2 formation)Thus allopurinol decreases the uric acid level
Synthesis of inosine monophosphate
Requires 10 steps4 enzymes use ATPTwo N10-formyl-FH4 are used to donate carbons.Requires adequate dietary folate.
AMP–?-> IMP
AMP deaminaseNH4+ forms
Converts ribose-5-phosphate to PRPP
PRPP synthetase
megaloblastic anemia
cell division impaired due to inadequate folate
The product of adenine degradation
hypoxanthine
IMP
inosine monophosphate
its synthesis is catalyzed by GPA
5-phosphoribosylamine
the precursor for both AMP and GMP
IMP
NAME?
Vitamine B12 or cobalamin
If intracellular [PRPP] and [Gln] are usually below GPA’s Km, then an increase in their concentration leads to …
an increase in de novo purine synthesis
Source of carbon for purine synthesis
two N10-formyl-FH4’s
The product of guanine degradation
xanthine
GPA
glutamine phosphoribosyl amidotransferase
Impaired cell division as a result of inadequate folate
megaloblastic anemia
PRPP reaction with glutamine to form
phosphoribosylamine
ribose moiety
purine base is synthesized on it
C8 and C2 are added by —— to the growing purine precursor.
Formyl-FH4
committed step in purine synthesis
PRPP + Gln —> 5-phospshoribosylaminecatalyzed by GPA-glutamine phosphoribosyl amidotransferase
xanthine oxidase requires —– to oxidize hypoxanthine.
molybdenum
The base of the first purine nucleotide
Hypoxanthine
PRPP synthetase
converts ribose-5-phosphate to PRPP, a ribose moiety on which purine is synthesized
The degradation of adenine produces hypoxanthine, which is oxidized to xanthine by ———.
xanthine oxidase
The reason that the first step of purine synthesis is regulated on the level of substrate
bc intracellular [PRPP] and [Gln] are usually below GPA’s Km.
It can result in high turnover tissues damage, producing megaloblastic anemia, diarrhea and glossitis.
Vit. B12 deficiency in which folate gets sequestered as 5-methyltetrahydrofolate and can’t be used in purine synthesis.
PRPP
5’-phosphoribosyl 1’-pyrophosphate
AMP
Adenosine monophosphate
Synthesis of phosphoribosylamine is catalyzed by
GPA- glutamine phosphoribosyl amidotransferase
The condition in which folate gets sequestered as 5-methyltetrahydrofolate and cannot be used in purine synthesis.
B12 deficiency
the reduction of the ribose moiety to deoxyribose occurs at ——— level, and is catalyzed by ——– which requires thioredoxin.
at diphosphate level and catalyzed by ribonucleotide reductase (RR)
the base of inosine monophosphate (IMP)
hypoxanthine
B12 deficiency and its impact on tetrahydrofolate
tetrahydrofolate can not be generated from 5- methyltetrahydrofolate
the sequence of degradation of purine nucleotides
phosphate and ribose are removed first, then the nitrogenous base is oxidized.
The first step in purine biosynthesis produces N9 of the purine ring and is inhibited by ——- and ——-.
AMP and GMP
The first purine nucleotide
inosine monophosphate