Biochemistry-II - Purines and Pyrimidines

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Study GuideBiochemistry-IIPurines and Pyrimidines1.Purine and Pyrimidine StructuresIntroduction to Nitrogenous BasesDNA and RNA are made from small building blocks callednitrogenous bases. These bases aredivided into two main groups:pyrimidinesandpurines.Even though they are both essential for nucleic acids, their structures and metabolic pathways aredifferent.Pyrimidine BasesPyrimidineshave asingle, six-membered ring.This ring containsfour carbon atomsandtwo nitrogen atoms.The three main pyrimidine bases are:CytosineThymineUracilEach of these bases has a slightly different arrangement of atoms, but all share the same basic ringstructure.

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Study GuidePurine BasesPurinesare larger than pyrimidines.They have adouble-ring structuremade up of:Onesix-membered ringOnefive-membered ringTogether, purines containnine atoms, includingfive carbonsandfour nitrogens.

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Study GuideThe two main purine bases are:AdenineGuanineThese bases are essential components of DNA and RNA.Key Differences Between Purines and PyrimidinesAlthough both purines and pyrimidines include a six-membered ring with nitrogen atoms, they arenotmetabolically related.This means:Purine biosynthesis and degradationfollow separate pathwaysPyrimidine biosynthesis and degradationfollow different pathwaysThese distinct pathways are found inall living organisms.

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Study GuideNucleosides and NucleotidesWhat Is a Nucleoside?When afive-membered sugar (carbohydrate) ringcombines with apurine or pyrimidine base,the molecule is called anucleoside.Important points:The atoms in the base are numbered normally.The sugar carbons are numbered using aprime (′) symbol(for example, 1′, 2′, 3′).This helps distinguish sugar atoms from base atoms.Examples of nucleosides include:Deoxyguanosine2′-O-methyladenosineWhat Is a Nucleotide?Ifone or more phosphate groupsare added to a nucleoside, the molecule becomes anucleotide.For example:3′-cytidine monophosphateis a nucleotideATP (adenosine triphosphate)is also a nucleotide and plays a major role in energy transferin cells

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Study GuideKey TakeawaysPyrimidines: single six-membered ring (Cytosine, Thymine, Uracil)Purines: double-ring structure (Adenine, Guanine)Nucleoside= base + sugarNucleotide= nucleoside + phosphatePurines and pyrimidines haveseparate metabolic pathways2.Salvage and Biosynthetic Pathways of NucleotidesOverview: How Cells Get NucleotidesCells need a constant supply ofnucleotides and nucleosides. These molecules are essential for:MakingDNA and RNAActing asenergy carriers(like ATP)Serving assignalingmoleculesForming parts of important cellular compoundsCells can obtain nucleotides inthree main ways:1.Salvage pathwaysrecycling existing bases2.Biosynthesis (de novo synthesis)building nucleotides from small precursors

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Study Guide3.Degradation pathwaysbreaking down excess nucleotidesThese three pathways are closely connected and work together to maintain balance in the cell.Why Balance Is So ImportantNucleotide balance is critical for normal cell function.DNA requiresequal amounts of A and T, andequal amounts of C and GRNA also needs balanced nucleotide levelsToo few nucleotides → DNA and RNA synthesis slows or stopsToo many nucleotides → toxic effects, especially from purinesBecause purines and purine nucleosides can be toxic to humans,excess purines must be safelyremoved.Salvage Pathways: Recycling NucleotidesConstant Turnover in the CellInside cells, DNA and RNA are constantly being:SynthesizedRepairedBroken downDuring DNA repair, parts of DNA are temporarily broken into:Free basesNucleosidesNucleotidesInstead of wasting these components, cellsrecycle them using salvage pathways.Role of PRPP in SalvageA key molecule in salvage pathways isphosphoribosyl pyrophosphate (PRPP).

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Study GuidePRPP is made fromribose-5-phosphateRibose-5-phosphate comes from thepentose phosphate pathwayPRPP acts as anactivated ribose donorPRPP is not only important for nucleotide metabolism but also activates other nitrogen-containingbiosynthetic pathways.Figure 1

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Study GuideSalvage EnzymesDifferent enzymes recycle different bases:One enzyme salvagesguanine or hypoxanthineA second enzyme salvagesadenineA third enzyme is specific foruracil and thymineAll these enzymes perform the same basic reaction:They transfer afree baseto PRPPThe product is anucleoside-5′-monophosphate (NMP)Purine Biosynthesis (De Novo Pathway)General StrategyIn purine biosynthesis:Theribose-phosphate backbone (from PRPP)is formed firstThepurine ring is built step by step on this backboneThe final product of this pathway isinosine monophosphate (IMP).

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Study GuideFirst Step: Formation of PRAThe first committed step is:Transfer of anamide group from glutamineto PRPPPyrophosphate is releasedThe product isphosphoribosylamine (PRA)Building the Purine Ring (Step-by-Step)1.Glycineis added to PRA→ forms glycinamide ribonucleotide2.The amino group of glycine isformylatedoFormyl group comes fromN¹⁰-formyltetrahydrofolate
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