BIOCHEMISTRY BIOCHM LEC BACHELOR OF MEDICAL LABORATORY SCIENCE | PRELIMS TOPIC 1: Basics of Biochemistry 1. Biochemistry speaks of Biodiversity variety of different lifeforms on earth, not only in humans DIVERSITY: genetic variation, ecosystem, species variation. INTERRELATED: due to the similarity in biomolecules that makes up their existence. All together, we use energy. H2O, CH4, CO2, NH3, N2, H2 2. Biochemistry speaks of diverse biochemical pathways Biochemistry is versatile and diverse. Attracts a multitude of disciplines in the scientific community. The understanding of the Molecular activities and pathways within the cells allowed medical practitioners to EFFECTIVELY TREAT DISEASES. Pathways occur simultaneously: some molecule have a single role while others have multiple roles. 5. Biochemistry and Biomolecules Biomolecules are composed of biologically important “Functional Groups”. Formation of ATP is one of the most important biochemical processes in species. Gases present in the atmosphere of the earth included: NH3, H2S, CO, CO2, CH4, N2, H2, and H2O. Formation of biomolecules happened ABIOTICALLY. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA Paroxysm: sweating, chills, fever Nocturnal: paroxysm occurs at night Hemoglobinuria: Hemoglobin (protein in RBC) is present in urine. If there is an early damage in RBC, hemoglobin will be released in the circulation. RBC will be destroyed, chills and fever at night, black urine at morning (occurs at night because compliment proteins are more active at acidic ph.) Small survival rate Deadly disease Caused by acquired membrane mutation ↑CO2 increase because of Hyperventilation during sleep Urine appears black because it is oxidized because it spends more time in the Urinary bladder. 3. 4. Biochemistry speaks about structure and organization Cascading formation from SIMPLE → COMPLEX. Biochemistry and ORGANIC CHEMISTRY They used to believe that life is held by a vital force (Vitalism) Molecules that are found in living organisms are exclusively found among living organisms and do not arise from non-living particles. (Old belief) ORGANIC CHEMISTRY: The study of compounds of carbon, especially of carbon and hydrogen and their derivatives. Side Note: It was previously thought that in the 19th century, vital forces (molecules unique to living things cannot be prepared/ made “in vitro”) Theory (above) was disproved by Friedrich Wohler in 1828 he was able to synthesize urea from ammonium cyanate in the laboratory. Padayon, fRMT! 1 MILLER- UREY EXPERIMENT The formation of polymerization of monomers have a sense of “Directionality” which comprises a cascade of events. ↓ all building blocks have a head and a tail. The effect of monomer sequence affects the properties of polymers Therefore, dictating its biological function. ENZYME: increases the rate of chemical reaction → Catalytic activity CATALYSIS: Depends on the sequence of amino acids. Miller-Urey Experiment: proved that biomolecules happened abiotically. Recent works suggest that RNA, not proteins, as the first genetic molecules. The possibility to synthesize nucleotides from simpler molecules using a Precursor that is not a sugar nor a nucleobase. Chemicals in earth befpre life (2aminooxazole) Arabinooxazoline (Phosphate) RNA nucleotide 2-aminooxazole: - A fragment consisting of a sugar and a part of a base. - Highly volatile molecules (Easily vaporized) - Condensed to give back pockets of pure materials ↓ produces Arabinooxazoline Nucleotides present before was destroyed because of excessive amount of UV Rays. Living cells consists of assembly of Very Large Molecules: WHAT DICTATES THESE SEQUENCE OF AMINO ACIDS? 1) Amino Acids → Peptides → Proteins 2) Nucleotides → Nucleic Acids 3) Monosaccharides → Polysaccharides 4) Glycerol and Three Fatty Acids → Lipids MONOMERS: small molecules that may bonds to form a polymer. POLYMERS: large molecules/macromolecules that are formed through bonding of smaller units. INFORMATIONAL MACROMOLECULES: sequence of monomeric units that contains information. Amino Acid Sequence is based on the Nucleotide sequence. The DNA serves as the storage of all information needed to synthesize protein in the body. Decoded by mRNA. mRNA is processed by ribosomes. Translation process happens in ribosomes, different sequences of amino acids are created using the different information found in the DNA. Ribosomes: Site of protein synthesis. From Molecules to Cells: If there is a mistake in the sequence of DNA, it will have a repercussion in the sequence of amino acid and it will alter the functionality of the protein. If the functionality of the protein is altered, it will have an impact to the entire system of the set. Impairing its general function. Past Theory: It was though that catalytic activity is limited with proteins. Recent Developments: RNA is capable of catalyzing its own reaction (RNA WORLD THEORY) Key point: Formation of membranes that separated the cells from their environment. Padayon, fRMT! 2 This membrane makes communication and internal pathway processes more efficient within the cell. WARM SIDE OF THE POND: - DOUBLE ORIGIN THEORY: 1. 2. - Rise of aggregates of molecules for catalysis Rise of nucleic acid based coding system Protocell moves to the warm side where the strand separates. The membrane incorporates more lipid molecule to the strand. The protocell divides with a single stranded RNA in each daughter cell and repeats the cycle. 6. 7. Biochemistry and Origin of Life We are the only life sustaining planet in the Universe. The Big Bang Theory: A tremendous explosion happened. A “primordial fireball” started to expand with great force. Composed of: Hydrogen. Helium, and Lithium Proposed formation of the other elements: (1) Thermonuclear reactions (2) In explosion of stars (3) Action of cosmic rays Evolution of Replication 8. Biomolecules to Single Cell Organisms CLAY PARTICLES Clay particles dictated the process of replication and the formation of protocells. Protocells exist in a pond with two sides: Cold and Warm side of Pond. COLD SIDE OF THE POND: - Double stranded polynucleotide on a single stranded template JOURNEY TO THE MODERN CELL After life got started, competition among lifeforms fueled the drive toward ever more complex organisms. We may never know the exact details of early evolution, but there is a plausible sequence of some of the major events that led from the first protocell to DNA-based cells such as bacteria. Padayon, fRMT! 3 1) EVOLUTION STARTS The first protocell is just a sac of water and RNA and requires an external stimulus (such as cycles of heat and cold) to reproduce. But it will soon acquire new traits. 2) RNA CATALYSTS Ribosomes – folded RNA molecules analogous to proteinbased enzymes- arise and take on such jobs as speeding up reproduction and strengthening the protocells membrane. Consequently, protocells begin to reproduce on their own. 3) METABOLISM BEGINS Other ribozymes catalyze metabolism – chains of chemical reactions that enable protocells to tap into nutrients from the environment. 4) PROTEIN APPEAR Complex systems of RNA catalysts begin to translate strings of RNA letters (gene) into chains of amino acids (proteins). Proteins later prove to be more efficient catalysts and able to carry out a variety of tasks. 5) 6) 7) A Comparison of Prokaryotes and Eukaryotes Organelle Prokaryotes Eukaryotes Nucleus No definite Present nucleus: DNA present but not separate from rest of cell Cell Membrane Present Present (Plasma Membrane) Mitochondria None; enzymes for Present oxidation reactions located on plasma membrane Endoplasmic None Present Reticulum Ribosomes Present Present Chloroplasts None; Present in Green photosynthesis (is plants present) is localized in chromatophores PROKARYOTES PROTEINS TAKE OVER Proteins take on a wide range of tasks within the cell. Protein-based catalysts, or enzymes, gradually replace most ribozymes. THE BIRTH OF DNA Other enzymes begin to make DNA. Thanks to its superior stability, DNA takes on the role of primary genetic molecule. RNA’s main role is now to act as a bridge between DNA and proteins. BACTERIAL WORLD Organisms resembling modern bacteria adapt to living virtually everywhere on earth and rule unopposed for billions of years, until some of them begin to evolve into more complex organisms. EUKARYOTES Prokaryotes and Eukaryotes Prokaryotes Closely linked to primitive cells are the “PROKARYOTES.” Greek derivation: “Karyon” = kernel. Nut. Literally means “Before the nucleus”. Comprises of two organisms: Bacteria and Cyanobacteria Eukaryotes Modern, complex, that can be multicellular or singlecelled (yeasts and paramecium). Means “true nucleus.” Eukaryotes has a nuclear membrane. Fact: eukaryotes evolved from eukaryotes about 1.5 billion years ago. Has a nuclear region contained genetic material and has the essentially the same function as the nucleus in a Eukaryotic Cell. Nuclear region: single, closed, circular molecule of DNA (Attached to the Cell Membrane) One Copy of the DNA is passed to the two daughter cells. Cytosol: has a slightly granular appearance due to the presence of ribosomes (also known as ribonucleoprotein particles) The only kingdom is MONERA. UNICELLULAR Has subcellular organelles; Important: nucleus, mitochondrion, *chloroplast (plants). Chloroplast: found in green plants and green algae, sites of photosynthesis. NOTE: Mitochondria and Chloroplasts contain DNA. Have their own transcription and ability to synthesize proteins. MULTICELLULAR ORGANELLES 1.) Nucleus MOST IMPORTANT ORGANELLE Surrounded by a “nuclear membrane.” Rich in RNA 2.) Mitochondrion SECOND most important organelle Outer Membrane: Smooth Inner Membrane: Cristae SPACE within these two membranes is called the Matrix. Powerhouse of the cell Processes of ATP Padayon, fRMT! 4 3.) Endoplasmic Reticulum Single membrane system throughout the cell Attached to both nuclear and cellular membrane. 4.) Golgi Apparatus Found close to the smooth endoplasmic reticulum. Secretion of proteins in the cell. Important for cellular content packaging. A better understanding in the mechanism of nucleic acids gives us further understanding of genetic diseases. Protein gives us understanding diseases of diseases which give rise to protein errors such as sickle cell anemia. Understanding the lipids gives us better understanding of atherosclerosis. Carbohydrates gives us better understanding of Diabetes Mellitus. CLASSIFICATION OF ORGANISMS Different organisms are classified into different kingdoms. BIOCHEMISTRY AND MEDICINE Knowledge of the biochemical topics has clarified our understanding of the diseases. Conversely, analyses of the diseases have casted light on many areas of biochemistry. Padayon, fRMT! 5