المساعد الشخصي الرقمي

مشاهدة النسخة كاملة : Biosynthesis of Nucleotides


yaak
02-09-2007, 11:17 PM
Biosynthesis of Nucleotides

Nucleotides play important roles in many biochemical processes, including:

They are the activated precursors of DNA and RNA.
They help form activated intermediates such as UDP-glucose and CDP-diacylglycerol, used in the biosynthesis of glycogen and phosphoglycerides, respectively.
ATP is used as the universal currency of energy.
Adenine is a component of coenzymes such as NAD+, FAD, and coenzyme A.
cAMP serves as a metabolic regulator. The activity of enzymes can be modified by phosphorylation and adenylylation.
Nucleotides can be synthesized from scratch or built from salvaged components. Purine and pyrimidine rings are formed from amino acids, tetrahydrofolate derivatives, ammonium and carbon dioxide. Ribose sugars are generated from the pentose phosphate pathway. The purine rings are assembled on the ribose sugar moiety to generate the ribonucleotides. Deoxyribonucleotides are then made by a dehydroxylation reaction. Pyrimidine rings are assembled first, and then attached to the ribose moiety. As with purine nucleottides, the deoxyribonucleotides are produced from ribonucleotide precursors.

purine

The purine ring is made from amino acids, tetrahydrofolate derivatives, and carbon dioxide:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/PurineOrigins.gif

The ring is assembled while being attached to ribose phosphate. The first step is the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP), an activated form of ribose:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/PRPPSynthetase.gif

The committed step in purine biosynthesis is the formation of 5-phophoribosyl-1-amine from PRPP and glutamine:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/PhosphoribosylAmine.gif

The basic purine ring which is formed is hypoxanthine, attached to the ribose-P unit it is called inosinate (IMP). The biosynthesis of this compound is carried out in several steps. In the first step, glycine forms an amide bond with 5-phosphoribosyl-1-amine in a reaction which consumes ATP. A formyl group from formyltetrahydrofolate is added, and an amidine group originating from glutamine replaces the keto group from glycine. Dehydration of this molecule forms a five-membered ring:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/InosinateBiosynthesis1.gif

A carboxylation reaction with this five-membered ring (using a non-biotin containing enzyme) is followed by the formation of another amide bond, this time with aspartate. The carbon atoms of aspartate are removed as fumarate, leaving only the nitrogen atom as an amino group. Another formyl group from formyltetrahydrofolate is added, and a six-membered ring is formed through another dehydration reaction, resulting in an inosinate molecule:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/InosinateBiosynthesis2.gif

Inosinate is the precursor of AMP (adenylate) and GMP (guanylate):

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/AMPandGMP.gif

The synthesis of the purine nucleotides is regulated by cumulative feedback inhibition:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/PurineFeedback.gif

Note also that ATP is used in the biosynthesis of GMP and GTP is used in the biosynthesis of ATP, a feature which helps to balance the synthesis of these compounds.

In addition to de novo synthesis, purine rings can be scavenged, regenerating nucleotides by the addition of the free base to 5-phosphoribosyl-1-pyrophosphate (PRPP) in a reaction which releases pyrophosphate:

Adenine + PRPP adenylate + PPi
Hypoxanthine + PRPP inosinate + PPi
Guanine + PRPP guanylate + PPi



pyrimidine

Unlike the purine nucleotides, pyrimidine rings are not synthesized while attached to ribose. Instead, the biosynthetic pathway produces orotate, a pyrimidine ring which is then attached to ribose in the form of PRPP, in a reaction analogous to the scavenging reaction of purine rings. Orotidylate produced in this manner is then converted to the pyrimidine analogs used in DNA and RNA.

The first step in pyrimidine synthesis is the production of carbamoyl phosphate, a component of the urea cycle. In prokaryotes, free ammonium can be used, but in eukaryotes the reaction to produce carbamoyl phosphate is carried out in the cytosol by a different mechanism which uses glutamine as the nitrogen donor and consumes 2 ATP:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/EukaryoticCarbamoylSynth.gif

The committed step in pyrimidine biosynthesis is the production of N-carbamoylaspartate through the formation of an amide bond between carbamoyl phosphate and aspartate. A dehydration reaction forms the six-membered ring of dihydroorotate which is oxidized to orotate:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/OrotateSynthesis.gif

A ribose-phosphate group is added to orotate to produce orotidylate, and this compound is decarboxylated to produce uridylate:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/UridylateSynthesis.gif

The mono-, di-, and triphosphate forms of nucleotides are interconvertible. The monophosphates can be converted to diphosphates in a reaction which uses ATP as the phosphate donor, producing two diphospates:

NMP + ATP http://138.192.68.68/bio/Courses/biochem2/MainPageResources/DoubleArrow.gif NDP + ADP

Diphosphates are converted to triphosphates by phosphorylation from another triphosphate, swapping the phosporyl group:

XDP + YTP http://138.192.68.68/bio/Courses/biochem2/MainPageResources/DoubleArrow.gif XTP + YDP

where X and Y are any of the ribo- or deoxyribonucleotides.

The reaction to producing cytidine nucleotides uses UTP as a precursor and glutamine as the nitrogen donor:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/CTPSynthesis.gif


The precursors of all the deoxyribonucleotides are the ribonucleotides described above. Ribonucleotide reductase converts the ribonucleoside di- and triphosphates to deoxyribonucleotides. The ultimate electron donor in this reaction is NADPH, but the electrons are passed through a complex series of carriers, including a flavin, sulfhydryl groups, an iron component, a tyrosyl radical, and another pair of sulfhydryl groups:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/RibonucleotideReductase.gif

Thymine, used as a base in DNA but not RNA, is made by a methylation of deoxyuridylate (dUMP) to produce deoxythymidylate in a reaction which uses N5, N10-methylenetetrahydrofolate as the carbon donor:

http://138.192.68.68/bio/Courses/biochem2/GeneIntro/GeneIntroResources/TMPSynthesis.gif

اتمنى اني غطيت الموضوع بشكل كامل . . . شكرا لمتابعتكم

روووح
02-10-2007, 08:31 AM
ممتااااااااااااااز
عملت لنا مراجعه
هذا الموضوع من اكثر المواضيع اعاده وتكرارفي كذا ماده في قسم الكيمياء الحيويه
بالتوفيق

yaak
02-10-2007, 02:47 PM
شكرا الهـwhidahـويد على ردك ... والحقيقه هذا الموضوع قد يدخل في مقررات البيولوجيه وقد يدخل في مقررات الايض بس مهم هذا الموضوع في علاج السرطانات اثناء تثبيط انزيم
thymidylate synthase بواسطه 5-FU وبذلك يرتبط الفلور في مكان مجموعه الميثيل على مركب Thymine ويوقف تصنيع Thymine

شكرا اختي على مرورك :friends:

نسايم
02-20-2007, 03:11 PM
تثبيط سرطان معين اكيد مش كل السرطانات
صح ؟؟

وشكرا للموضوع الحلو

yaak
02-20-2007, 06:31 PM
مشكوره اختي نسايم على هذا الرد الجميل

اضيف لك معلومه

يثبط جميع السرطانات لانه يثبط في المسار الرئيسي لتصمينع Thymine
وهو نفس العلاج عن طريق الكيماوي

وراح تتوقف تصنيع جميع البروتينات من شعر وغيرها

شكرا اختي على مرورك :rabbi:

ملكــة الصــمت
02-22-2007, 01:20 AM
تشكرات للموضوع المهم ...

yaak
02-22-2007, 01:43 AM
العفو ملكة الصمت
واشكرك على المرور والتعليق :rabbi: