BMB 462 Lecture 17 Outline of Last Lecture I Continuation of Hormone Classification a Mode of Action b Release point Target tissue II Hormone Signaling III Specialized metabolic function of tissues a The liver b The pancreas IV Insulin a Control of Secretion b Effects function of insulin V Effects of Glucagon VI Metabolism under starvation conditions VII Effects of Epinephrine VIII Effects of Cortisol Outline of Current Lecture I Nucleotide structure and nomenclature a i e dAMP II Nucleotide properties III Nucleotide Function IV Nucleotide Metabolism a Regulation of metabolism Current Lecture Concepts to remembers from previous courses lectures I Nucleotide structure and nomenclature a Nucleotides are carriers of information in the cell i They store information in the DNA and that is transmitted and translated into RNA from which proteins are made b They also serve as energy carriers in the cell These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute c Nucleosides have a pentose sugar and a base attached If there is also a phosphate on the 5 atom they re called nucleotides can have up to 3 phosphates d 5 nitrogenous bases in cells they are either pyrimidines or purines e Mnemonic that may help you remember purines vs pyrimidines i Purine Purina dog chow which is from an agricultural company AG adenine and guanine You should always buy 2 bags 2 rings ii Pyrimidines Cut a single pyramid CUT Cytosine thymine uracil f i e dAMP i In Purines the bases are attached via Nitrogen 9 to the sugar Base atoms are labeled 1 9 sugar atoms are labeled 1 5 to distinguish them from base atoms ii Base is attached to sugar by N glycosidic bond The bond can rotate so have syn orientation both the base and the sugar are on the face of bond Anti conformation is base and sugar on opposite sides Most NMPs in DNA are in the anti conformation iii The bond forms on the C1 anomeric carbon of the sugar The anomeric carbon is in the beta configuration which means that the OH that originally helped form the bond is pointing upwards so you can also call it an N beta glycosidic bond iv An adenosine has an OH at the 2 position v Deoxyadenosine does not have that hydroxyl group vi When you add the phosphate group to the 5 of deoxyadenosine you get deoxyadenosine 5 monophosphate aka deoxyadenylate or dAMP g The base is flat while the sugar is not The flatness allows the bases to stack in the core of the DNA helix and that makes the DNA very strong h The faces of the base are hydrophobic making hydrophobic stacking structure The edges are polar which is what allows you to make hydrogen bonds and make base pairing to other bases Depending on what base you have you can make different hydrogen bonds i As each component of the nucleotide is added to the base the nomenclature changes i See table 8 1 page 3 of the lecture notes II Nucleotide properties a Absorption Spectra i All bases absorb light at 260nm this is due to the conjugated double bond in the bases which absorb light ii Use the absorption at 260nm to determine the concentration of bases iii This is useful in the lab b c you know that in double stranded DNA when the Absorption at 260 1 that s about 50ng uL You can use the absorption and that standard to calculate the concentration of DNA in a solution The concentrations for ssDNA and RNA are different iv Proteins absorb at wavelengths of 280 nm Compare absorption at 260 vs 280 to see how pure sample is b pH and tautomerization i An H bond donor is when an electronegative atom is bonded to the hydrogen and pulls away the e from the bond O H are very electronegative ii If it has a free electron pair it can become an H bond acceptor iii CH is none b c C has similar electronegativity to H iv pH can change the form of uracil When pH is low uracil switches from lactam to lactim formation The Hydrogen moves from the N to the O on atom 2 This changes the hydrogen bonding In lactam N is the donor and O is the acceptor in lactim N becomes the acceptor c H bonding and base pairing in DNA i Because information is stored in the hydrogen bonding of DNA it is important to have the right pH b c changing pH changes H bonding and you will lose the information ii AT has 2 H bonds and GC has 3 so GC is slightly more stable Otherwise they are almost identical structurally iii The H bonding neutralizes the charge inside the DNA so the inside of the DNA becomes hydrophobic Then bases stack on each other and create a hydrophobic core that is very stable iv The outside of the DNA the phosphodiester bonds between the sugar and the phosphate are hydrophilic III Nucleotide Function a Building Blocks i One of the most important roles of nucleotides is that they build DNA and RNA ii Central Dogma of biology is that DNA is replicated to make other copies of DNA and transmits information to a dividing cell so both daughter cells get the same DNA and the DNA is transcribed into RNA and RNA is translated into protein iii DNA and RNA are central to biology b Information storage and transfer i Information is stored in DNA and that is replicated and transferred through transcription into RNA RNA is then translated into proteins c Energy Carriers i Ribo nucleotides can also be used as energy carriers Mostly true for ATP and GTP So they can be building blocks or energy carriers ii deoxynucleotides are mostly just building blocks iii They are energy carriers b c the phosphoanhydride bonds are very high in energy so they are used by the cell to drive a lot of reactions d Coenzyme handles i The coenzymes often come from ATP ii CoA NAD and FAD all have nucleotides included in them e Signaling Molecules i Nucleotides can also be used in signaling molecules ii I e cAMP The 5 phosphate forms a cyclic bond w the 3 OH iii It s a signaling molecule inside the cell that acts as a secondary messenger Primary signals i e hormones are usually outside of the cell iv ppGpp is a secondary molecule used in bacteria IV Nucleotide Metabolism a Overview of Metabolism i Purines and pyrimidines are constructed differently de novo but both rely on the central molecule PRPP it s a central molecule in nucleotide metabolism and comes from the pentose phosphate pathway ii Bases are built attached to the ribose SO you start with PRPP and then add various atoms are to it the sources of the atoms are amino acid CO2 and THF iii It s important that in purines the bases are built
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