Nucleotides & Nucleic Acids
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1 Nucleotides & Nucleic Acids Nucleic Acids are complex, high-molecular-weight macromolecules composed of building units called nucleotides. Nucleic acids are found in all living cells and viruses. The most common nucleic acids are DNA (deoxyribonucleic acid) and RNA(ribonucleic acid. Differences between DNA & RNA's DNA RNA Location In the Nucleus In Nucleus & Cytoplasm Structure Double-stranded Single-stranded Bases A, T, C, G A, U, C, G Sugar Deoxyribose Ribose Function Carries the genetic material and is transcribed to give mrna. 3 types of RNAs: 1) mrna: carries genetic code from the nucleus to ribosomes in the cytoplasm. 2) rrna: forms 50% of the ribosome structure + 50% protein (histone). 3) trna: carries and directs amino acids to ribosomes (in translation process to give proteins). 1
2 Nucleotides: Each nucleotide consists of three components: 1) A nitrogenous heterocyclic base (either a purine or a pyrimidine). Purine bases include: Adenine (A) & Guanine (G) Purimidine bases: Guanine (G), Cytosine (C) & Thymine (T). Adenine Guanine Cytosine Uracil Thymine 2
3 2) A pentose sugar a) ribose b) deoxyribose. 3) A phosphate group. Nucleotide = Base + Sugar + Phosphate Nucleoside = Base + Sugar 3
4 Adenosine (Nucleoside) Adenosine monophosphate (AMP) 4
5 Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) 5
6 NAD + 6
7 FAD Biological Function of Nucleotides: 1. Nucleotides are the building units of nucleic acids (RNA & DNA). 2. Adenosine triphosphate (ATP) act as the energy carrier in the body. 3. Cyclic nucleotides, e.g. cyclic adenosine monophosphate (camp) act as second messengers to mediate hormone action. 4. Many nucleotides act as coenzymes that assist catalytic function of enzymes, e.g. nicotinamide-adenine dinucleotide (NAD), and flavinadenine dinucleotide (FAD). These coenzymes act as hydrogen carriers. N.B. Gout and hyperuricemia are related to defect in the metabolism of purine bases of nucleotides. Gout results from the accumulation of large amounts of uricacid in joints and perhaps in the kidney. 7
8 The Structure of DNA: In the DNA molecule the 2 strands are attached together by hydrogen bonds between bases: 2 hydrogen bonds between Adenine (A) and Thymine (T); 3 hydrogen bonds between Guanine (G) and Cytosine (C). The bases that form hydrogen bonds with each other are called complementary bases. 8
9 The Structure of RNAs: The 3 major types of RNA incells are: a) Messenger RNA (mrna). b) Ribosomal RNA (rrna). c) Transfer RNA (trna). 1. Messenger RNA (mrna): a) Is formed in the nucleus in a process called transcription. The process of transcription means the formation of mrna complementary to the gene sequence on DNA (in the nucleus) b) It carries the genetic code from the nucleus to the ribosomes in the cytoplasm. c) The nucleotides on mrna are read as 3 nucleotides during protein synthesis and these 3 nucleotides specify one amino acid. The 3 nucleotides are known as triplet codon (genetic code). 2. Ribosomal RNA (rrna): Ribosomal RNA (rrna) comprises about 50% of the mass of a ribosome, and the other 50% is composed of basic proteins, i.e. histones. The ribosomes are he site of protein synthesis. 3. Transfer RNA (trna): Transfer RNA (trna) molecules serve as carriers of activated amino acids during the process of translation. The process of translation means the formation of an amino acid sequence according the sequence of genetic code on mrna (in the cytoplasm) The Genetic Code, Protein Synthesis & Mutation Definitions: 1. The Genetic Code: a) Is composed of the 3 adjacent bases (triplets) in the mrna molecule that correlates with amino acids. b) Most amino acids are expressed by more than one codon, phenylalanine (Phe) for example, has 2 genetic codes: UUU and UUC; alanine is coded by 4 codes: GCU, GCC, GCA, GCG. c) Only 2 amino acids go with single codons: tryptophan (Trp) and methionine (Met) 9
10 First The Genetic Code Second Base Third Base U C A G Base Phe Ser Tyr Cys U U Phe Ser Tyr Cys C Leu Ser T.C T.C A Leu Ser T.C Trp G Leu Pro His Arg U C Leu Pro His Arg C Leu Pro Gln Arg A Leu Pro Gln Arg G Ile Thr Asn Ser U A Ile Thr Asn Ser C Iie Thr Lys Arg A Met Thr Lys Arg G Val Ala Asp Gly U G Val Ala Asp Gly C Val Ala Glu Gly A Val Ala Glu Gly G The genetic code shown in the above table is universal for all plants and animals. The triplet codons have the following characteristics: a) Each amino acid is expressed by a sequence of bases. b) Sometimes, there is more than one triplet to determine a single amino acid. Thecode in this case is described as "degenerate". c) The genetic code is not "punctuated", i.e. the code is read off from a given point, triplet by triplet, without the intervention of spacers like:, ;. -?! and so on. 10
11 Protein Synthesis In order to start protein synthesis the follwing components should be available: 1. Amino acids (the building units of proteins). 2. Transfer RNA (trna) which act as amino acid carriers. 3. The ribosomes, which act as the site of protein synthesis. 4. Messenger RNA (mrna), which directs the whole process by the codons it carries. 5. ATP and GTP, which act as energy sources. 6. Codons for initiation (start) and termination (stop) of the process of protein synthesis. Stages of Protein Synthesis: There are 3 stages in the synthesis of proteins: 1. Initiation: starts as the initiation codon (AUG) comes into play. 2. Elongation: means the formation of the poly[eptide chain by adding one amino acid after he other in a sequence dictated by he geneticcode sequence. 3. Termination: means the stop of protein synthesis when one of the 3 possible termination codons appear (AUA, AUG & GUA). Mutations Mutations are permanent alteration in the sequence of bases in chromosomal DNA. If mutations occur in germ cells, the subsequent generations are affected, whereas if mutations occur in dividing somatic cells, the relevant mature tissues are affected. 11
12 The 2 most striking modes of mutation are "point" and "frame shift" mutattions. 1. Point Mutations: These result from the replacement of one base by another; e.g. sickle cell anemia, where in the B chain of hemoglobin glutamic acid is replaced by valine at position number 6. This change results in sickling of red blood ells. Normal adult hemoglobin (HbA): HbA : Val His Leu Thr Pro Glu Glu Lys Sickled hemoglobin (HbS): HbS : Val His Leu Thr Pro Val Glu Lys - 2. Frame Shift Mutations: In this type of mutation deletion or insertion of a base anywhere along the sequence results in the misreading of the codes. A frameshift mutation causes the reading of codons to be different, so all codons after the mutation will code for different amino acids. Furthermore, the stop codon "UAA, UGA, or UAG" will not be read, or a stop codon could be created at an earlier site. The protein being created could be abnormally short, abnormally long, and/or contain the wrong amino acids. Examples are thalassemias. 12
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