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Biology Lectures – winter term 2008 1st year of Pharmacy study 3rd Lecture Chemical composition of living matter – chemical basis of life. Atoms, molecules, organic compounds – carbohydrates, lipids, proteins, nucleic acids Atoms -protons,neutrons,electrons electrons electrons Macroelements H,O,C,N,P,S,Na,K,Cl,Fe,Mg Microelements I,Mn,F,Zn,Cu,Co,Se,....... Bonds of atoms Molecules Bond – ionic, covalent, polar and non-polar metán Sodík Chlór NaCl H2O ATP - energy - Structure of Nucleic acides - signal molecule Macromolecules - sugars -saccharides - lipids - proteins - nucleic acids Sugars - saccharides Monosaccharides - pentose – ribose, deoxyribose - hexose – glucose, fructose, galactose Sugars - saccharides disascharides - saccharum, maltose, lactose Sugars - saccharides Polysaccharides - starch, glycogen, cellulose glucose glucogen Proteins Proteins Proteins biogenic amino acids, names a codes Aspartic Acid Phenylanine Alanine Histidine Lysine Methionine Proline Arginine Threonine Tryptophan Asp Phe Ala His Lys Met Pro Arg Thr Trp D F A H K M P R T W Glutamic Acid Glycine Cystine Isoleucine Leucine Asparagine Glutamine Serine Valine Tyrosine Glu Gly Cys Ile Leu Asn Gln Ser Val Tyr E G C I L N Q S V Y Amino acids Amino acids sequence 3-D structure Function of protein Genetic code Proteins Peptide bond Proteins Folding of proteins Amino Acid Sequence 3-D Structure Protein Function α, β−Helix pleadted sheet 3-D structure of proteins 1. Primary structure – amino acids sequence (determine by mRNA) 2. secondary – α-or β-helix; pleated sheet (H-bonds) 3. Tertiary – 3-D protein structure (S-S bonds) 4. Quaternary – the final structure of proteins (subunits, prostetic units and etc.) 3-D Structure of proteins Three ways of proteins bonds Proteins are hungry Amino Acid Sequence 3-D Structure Protein Function Nucleic acids DNA-RNA Nucleic acids DNA Chromosome Nucleus consists one or more molecules DNA organized into chromosomes Human: – 22 pars autozomes – 1 par sex chromosome Human karyotypes Human and mouse chromosomes: DNA chemical structure Double helix of DNA Double helix • Two complementary DNA strains • Spring will be 52th anniversary of its discovery Detection of DNA Detection of DNA Red – increase of sample transcripts Green – increase of sample transcripts Yellow – equal abundance Limit of Detection: 1 in 30,000 transcripts ~ 20 transcripts/cell Affymetrix GeneChip® Limits: 1: 100,000 transcripts ~ 5 transcripts/cell Affymetrix GeneChip® 3-D Structure of DNA in nucleus Nuclear membrane Chromatin fiber Chromatin fiber (30 nm dia.) H1 Nucleosomes H1 } Nuclear pore Nuclear matrix DNA Other Chromatin factors DNA-protein complex DNA folding Chromatin structure Chromatin structure DNA is wrapped around histone proteins as chromatin The Obstacles are Regulated: Histone Modifications A Histone Code? Bromo Domain Chromo Domain • regulation of transcription • complex of genes to the DNA locus • protection of specific genes All cells – the same DNA - different reading of DNA - differentiation of cells Histones play Key role in Regulation of gene expression Transcription and Processing DNA in blue PolyA+RNA in red PolyA+RNA in red (a spliceosomal component) in green Overlap (red + green) = yellow RNA • Ribonucleic • Similar as DNA • Tymine (T) is substituted by uracile (U) • RNA can be: – One-strain helix – Double – strains helix – Hybridisated with DNA RNA • RNA is usually one strain • It forms the 3-D secondary and tertiary structure • The most important is extreme variability of the RNA molecules sequence tRNA: sequence, 3-D structure mRNA • Messenger RNA • Linear molecule coded genetic information – copy from DNA • Transcription: process of copy mRNA from DNA mRNA modification • Eukaryotic genes are built: • Exons: coding regions • Introns: non-coding regions • splicing: cut of introns from molecule of mRNA and link the exons • After this modification of mRNA is translated to sequence of protein mRNA modification Image source: http://departments.oxy.edu/biology/Stillman/bi221/111300/processing_of_hnrnas.htm tRNA • Transfer RNA • Precise 3-D structure • The translation process of protein tRNA structure tRNA • Specific tRNA for each amino acid • Determine by 3 nucleotide - anticodone (complementary with mRNA) • Translation: process of prescription of codons of mRNA to sequence of amino acids to protein tRNA tRNA: sequence, 3-D structure tRNA structure rRNA secondary structure 16S ribosomal RNA T. thermophilus - Ramakrishnan et al., Cell, 2002 Lipids Schematic Diagram of a phospholipid molecule (phosphatidylcholine) Phospholipids • Membranes of mammalian cells contain 3 major phospholipids – Classified according to the polar headgroup Choline head-group Polar Phosphatidylcholine Nonpolar Saturated fatty acid Unsaturated fatty acid Differences in the length and degree of saturation of fatty acids affect their ability to pack & hence the fluidity of the bilayer Amphipathic A, formula B, schematic drawing C, space-filling model Cholesterol is oriented in the membrane between phospholipid molecules with its polar end towards the outside surface of the monolayer and its hydrophobic end projecting into the interior of the membrane Lodish et al, Fig 5-30