Biochemistry and Cellular Foundations

Key Milestones in Biochemistry and Cellular Foundations

• 1896: Eduard Buchner demonstrates alcoholic fermentation in yeast cell extracts, marking the first complex biochemical process outside of a cell.
• 1953: James Watson and Francis Crick discover the double helical structure of DNA.
• 1953: Hans Adolf Krebs discovers the biochemical steps of the Krebs cycle in carbohydrate metabolism.
• 1957: Daniel Bovet receives Nobel Prize for developing antihistamines.
• 1959: Severo Ochoa and Arthur Kornberg receive Nobel Prize for discoveries on DNA and RNA synthesis.
• 1970: Hamilton Smith reports the discovery of the first restriction enzyme.
• 1975: Cesar Milstein, Georges Kohler, and Niels Kai Jerne develop the technique for making monoclonal antibodies.
• 1995: FDA approves the first protease inhibitor for AIDS treatment.
• 1997: First complete nucleotide sequence of a eukaryote's chromosomes (yeast) reported.
• 2001: NIH-funded human fetal ventral mesencephalic transplant clinical trials yield negative results.
• Principles 1 and 2: Cells are the fundamental unit of life and use a small set of metabolites to create structures and information repositories.
• Principle 3 and 4: Living organisms are in a dynamic steady state, not at equilibrium, and extract energy from their surroundings to maintain homeostasis.

Key Concepts in Biochemistry

• Trace elements, essential to life, are vital for the function of specific proteins and enzymes.
• Carbon is the central element in biomolecules, forming stable single bonds with up to four other carbon atoms.
• Carbon can form covalent single, double, and triple bonds, with the ability for free rotation around single bonds and limited rotation around double bonds.
• Biomolecules are derivatives of hydrocarbons with functional groups such as alcohols, amines, aldehydes, ketones, and carboxylic acids, each conferring specific chemical properties.
• Many biomolecules are polyfunctional, containing multiple types of functional groups, determining the compound's chemical characteristics and reactions.
• Cells contain a universal set of small molecules, including amino acids, nucleotides, sugars, and carboxylic acids, with secondary metabolites being specific to the organism.
• Macromolecules, such as proteins, nucleic acids, and polysaccharides, are the major constituents of cells, with proteins also functioning as enzymes, structural elements, and more.
• Proteins, nucleic acids, and some oligosaccharides serve as informational macromolecules, with the proteome representing the sum of all proteins in a cell.
• Nucleic acids, including DNA and RNA, store and transmit genetic information, while some RNA molecules have structural and catalytic roles in supramolecular complexes.
• Polysaccharides serve as energy-rich fuel stores, rigid structural components, and extracellular recognition elements, while lipids function as structural components of membranes and energy-rich fuel stores.
• Three-dimensional structure in biochemistry is described by configuration and conformation, with stereochemistry playing a crucial role in the interaction between biomolecules.
• Geometric isomers, or cis-trans isomers, have distinct biological roles despite their similar chemical makeup, exemplified by the visual pigment in the vertebrate eye, rhodopsin, containing retinal, a vitamin A–derived lipid.

Cellular Diversity and Organization

• Organisms are distinguished by their habitats and sources of energy, such as aerobic, anaerobic, obligate anaerobes, and facultative anaerobes.
• Bacteria and Archaea share common features but differ in their cell envelopes, with Gram-positive bacteria having a thick peptidoglycan layer and Gram-negative bacteria having an outer membrane composed of a lipid bilayer.
• Eukaryotic cells contain various membranous organelles, including mitochondria, endoplasmic reticulum, golgi complexes, peroxisomes, lysosomes, vacuoles, and chloroplasts.
• Subcellular fractionation involves disrupting cells and centrifuging the homogenate to isolate organelles enriched in specific enzymes, aiding in enzyme purification.
• The cytoplasm is organized by the dynamic cytoskeleton, consisting of actin filaments, microtubules, and intermediate filaments, which provide structure and organization to the cell.
• The endomembrane system segregates metabolic processes and facilitates transport mechanisms like exocytosis and endocytosis.
• Supramolecular complexes are held together by noncovalent interactions, such as hydrogen bonds, ionic interactions, van der Waals interactions, and the hydrophobic effect, producing unique structures.
• Studying isolated cellular components in vitro may overlook important interactions that occur in living cells, as molecules may behave differently in vivo and in vitro.
• Cells use a relatively small set of carbon-based metabolites to create polymeric machines, supramolecular structures, and information repositories.
• The observed universality of chemical intermediates and transformations supports the understanding that all organisms share a common evolutionary origin.
• The four most abundant elements in living organisms are hydrogen, oxygen, nitrogen, and carbon, which make up more than 99% of the mass of most cells, due to their ability to efficiently form strong bonds.
• The lightest elements form the strongest bonds, and the biochemical unity is based on the shared evolutionary origin of organisms.