Overview Notes (9) Related Modules

258 Molecular 44
Biology
METABOLISM OF NUCLEOTIDES

Purine metabolism 00:00:57

De NioVO Aurine suynthesis:

occurs in most of the tissues (cytoplasm) but mainiuy in the
iver.
De NOVO Sunthesis doesnt take place in : rain.
erytrocyte.
Leukocyte.
Bone narrow.
They purely depend on tthe Salvage pathuay
Cortributors to Purine rino The folie acid component in the
purine ring plaus an important role in cancer treatment and
its dehciency can cause defective DNA sunthesis.
Respiratory
Glycine

Rspartote

C SN N, metheny
THEA,

N
Feedback
tapubhuyan39332@gmait.c... Anide Nitrogen of
Glutamine

Steps of De Novo Purine synthesis

PRPP HO PPi
ehosphorib0sy
2ibose 5 synthetase Phosphor kosy ’ Amine
Phosphate ATe Ame pyroposphate elutamate

D (PRPP). Gjutamine

Inosine
ist Purine
Nucleotide monophosphate
(nnp).

Biocherrlstry v4.0 Marow 6.6 2023 Page 1/9

Overview Notes (9) Related Modules
44 Metaboism of 259
Nucleotides

Arnino aroup Aspartate Glutamine

Donor
Adenosine Guonosine
moophosphate nonophosphate
PRPP Sunthetase : Preliminary step
Reguiatory step
P8-SR370d693
Salvae pakAA
NAD' Sunthesis
Pyrimidine sunthesis
PReP GlutanuAninotransferase Committed stepof
purine synthesis
Regulatorystep
Rate limiting step
Salvage pathway 00:11:13

Purine nurieoside and Purine bases are recycled to Purine

nucieotides :

celil lysis

Purine nucleotide
GATP)
Lioose po,
Purine nuclecside

eiboseldesyibose
Purine base

uric acid

Features :
. Soves energy
a. etlectie recycing
3. important in orgors uwithout De nwo Purine sythesis,
Donor for Ribose od Po, : PRPe The reaction is caled
fhosphoribosyjaton.
Biochenistry v4,0 " Marow B.5 +2023
Page 2/9
Overview Notes (9) Related Modules

260 Molecutsr 44
Biology
Donor for o, ATR The reaction is called fhosphorlation.
Reactions :
HEPRTase, phosphor ibosus transferase
Phosphoribosylation
Pu >PuRp
HePRTase: Hypoxonthine Guanine PTase popp pp
a Hypoxanthine/ Guanin HGPRTase
y Inosine

monophosphatel quanosinemonoghosphate.
APRTase
b. Adenine Adenosine monophosphate
PRPP PPi

APRTase :Adenine Phosphoriboss| transferase.

a. Phosphorylation ATPADP hinase

Adenosine Kinase
Adenosine >Adenosine monophosphate

Purine catabolism 00:20:05

635975a7df22be2e5370d693
Ste:Dietary Purine degraded in :Intestine.
endogenous are degraded in Liver.
end product i uric acid. Organele Cytoplasm.
Steps of purine cotobolism :
Adenosine
Aderosine x scID
dearinase immunodeReiency disease
Feedback inosine
Purine nucleoside
X ELAanosine

ribosul translerase
Hypoxanthine auanine
Xanthine Equanine
X Oxidase deaminase
Xarthinu Xanthine
Xarthine
X oxickase
Uric aekd

Biochermístry v40 Marrow 6.5 2023

Overview Notes (9) Related Modules

44 Metabolism of
Nucleotides

SCID (Severe combined immunodetciency delect):

Adenosine deaminase deect.
Both &-oels $ T-cels are afected
ImmunodeAciency disease :
Purine nuACleoside riboss| transferase delect.
T-cells are affected -cells are normal.
" Xantthinuria:
Xarthine oxidase defect.
Xanthine crystals are seen with Hupouricemia.
Xanthine oxidase requires moybdenum.
Aliopurinol inhibits taRMbhuyan39332@gmail.comn
Disorders associated with Purine metabolism 00:25:46

HGPRTaSe deiciency?
L Lesch nyhan syndrome:

D
Feedback
Xlirvedrecessie dsorder.
eiochenical detect iHEPRTase completely delcient
Hypoxorthine/ Ime/
uanine
Purines accurulote irereased uric ackd Gyperuricemia)
Clinical features :
Computsive set-mutlotion.
Gout.

Biochemistry v4.0 Marow 65"2023

Overview Notes (9) Related Modules

262 Molecuiar 44
Biology
Dystonic movements.
megaloblastic anemia.
Neurological deRcit.
Treatment:
Allopurinol (inhibits xXanthine oxidose).
High tid diet.
Asalini2e urine.

a neleyseegmiller synrome
HaPRTAse is partialy defciert
>15-a% activity t
APRTase detcienCy
APRTase
Adenine -X’ Ame
Oxidotion PRPP PPi
a,8 dihydroxy adenine
tapabhujyan39332@gnaiteemria causin9
broun spots in the diaper.
Gout 00:31:36

Feedback uric acd erystals Ist metatar saythakas naqeai jont chronic qout

Topb onosodkafe
urate erystats in Neqativekybir et ingent
ur ic acd erystae.
Sahcautaneous tisue
(Seen in synoviai kuic)
 Overview Notes (9) Related Modules

44 Metabolism of
Nucleotides

Biochemical detect:
nprimary gout
Enzyme defect
‘Activity of PRAP Synthesis Purine furic
acid
Actvits of PRAP Glutamsl
asicdotransterase
Causes Lesch Nuhan sundrome.
Giuoose-phosphatase dehciency: Von Gijerke's
disease (Tupe iGsD)
" in secondary gout

Decreased excretion of
‘cell turnover
uric acid, Causes:
Lactic acidosis
maigraney Renal tailure
Aggrawating Ractors of gout Duretics (Thiazides)
Alcoholism
inereased Purine intoake (meat).
" Juk ood : Fructose
rich’Hyperuricemia
Symtoms of Gout:

Acute
Chronic
Acute ikiosmmatory Tophi
artr ts 635975a7df22be2e5370d693
uric acid nephroittiasis
Feedback
Dagoss of out Apration exarNaton of saynoval ucd
fro4 nonyaktects te rst tretatos sohalareai jont
kecouia the acd oykalzescyronly at th coki
TreatrBr:

" Prevent aggravatrg factors

Overview Notes (9) Related Modules
264 Molecular
Biology
SCID &Severe T-cell defect 00:40:25

sCID: Severe combinedimmunodeHciercy'

Defective enzyme :Adenosine deaminase.
most common cause :Defect in gamma chain of io
Non-homologous endjoining(NHED detective DhA repair)is
also a cause.
Both B-cells and T-cells are oaffected.
The Arst disorder to be treated loygene therapy oy or.
French Anderson Fatther of gene therapu).
Enzyme ReplacementTherapy (eRT):Polyethyjere gjycoi
modihedADA is aso atreatment modalty for sCiD.

Purinenucleoside phosphorylase defect

Severe T-cel detect and B-celsare apparenthy normal
Pyrimidine metabolism 00:45:27

Site Liver.
Organele : Cuytoplasn and mitochondria.
c835975a7df22be2e5370d693
Cytoplasm)Ces 1
CAO ENZume
carbamoy) fo, |(Singje polypephde)
Aspartate
Aspartate in Cytoplasm
Transcarbomouylase.
Feedback (ATC)
Carbanoy
Aspartate
Dihdroorotase
Dhydrocr ote acid
Didroorotate
NACH step
dehnydr ogenase
Orotic acd |rnttaset
OPRTase
PP
Orotate mropkosphate (on)
 verview Notes (9) Related Modules

44 Metabolisn of 265
Nucleotides
co, ome decarboxylase
uridine monophosphate áme):purimidine nucleotide
ATP Diribonuceotide
reductase
duDp
ATP
ADP
UTP dump
CTP Thumidjatemethyjene
sunthase ohydrofolate
THFA H Folatereductase
sunthetase
CTP TMP

SFAuorouracil inhibits Thumidujate synthase,

methotrexote inhibits Dihydrofolate reductase.
Orotic aciduria 00:56:22

Detect in the De NovO Suntthetic potthway of purimidines.

Autosoai recessve.
Tupe iOrotic aciduria:Defect in bifunctional enzume um
synthase.
Deereased ump surthase leods to decrease in cCTP TNP.
Resuitrg in decreosed pyramidines ’ decreased DNA
syntress macroaytc anemia.
Tupe norotic ociduria:Delect in omp decarboxulase onls

end products o Pymidine catabolem :

cytone
Feedback Thynne

TrerekorG35975atdf22bezè6370d693
e trey do not ystalize ard os t o s Seen

Cartaroy o, sntochorxd a)
Jerview Notes (9) Related Modules

66 Molecular 44
Biology
Qeye's sundrome:
Delect in mitochondrialen2ues (urea cycie enzunes).
nereased CP leads to orotic acidurio.
Pseudöuridine:
#is found in the pseudouridine arm of tRNA,
uidne üract +Ribose Sugar
Pseudouridne C,Aur t cPentosesugar.
Purimidine Salvane pathuay
Primidine nucleotide

Purimidine nucleoside

Pyrmidine base

Case
Aimonth oid chid presented with faikure to thrive, macrocutic
exomination shouwed
huypochromic anemio. Bone marrow
Acid or iron
megaiobiast. No response to Vitamin B1a or Folic
what is your diagnoss?
Ars. orotic Aciduria

tapubhuyan39332@gmail.com