biochemistry

• The quaternary structure of a protein refers to the arrangement of multiple polypeptide chains in a protein complex.
• Biochemistry is the study of the structure, organization, and function of living matter in chemical terms
• Biochemistry aims to understand how lifeless molecules interact to create the complexity and efficiency of life phenomena
• Biochemistry explains the diverse forms of life in chemical terms
• Biochemistry brought about the molecular revolution of biology in the 20th century
• Topics addressed by Biochemists:

  • Chemical structures of the components of living matter
  • Interactions of these components that give rise to organized supramolecular structures, cells, multicellular tissues, and organisms
  • Extraction of energy by living matter from its surroundings to remain alive
  • Storage and transmission of information for living matter to grow and reproduce accurately
  • Chemical changes that accompany the reproduction, aging, and death of cells and organisms
  • Control of chemical reactions inside living cells
• Some major events in the history of Biochemistry:

  • 1828: Wohler synthesized urea from ammonium cyanate in the lab
  • 1897: Buchner demonstrated fermentation with cell extracts, in vitro study began
  • 1926: Sumner crystallized urease
  • 1944: Avery, MacLeod, and McCarty showed DNA to be the agent of genetic transformation
  • 1953: Watson and Crick proposed the double helix for DNA
  • 1959: Perutz determined 3-D structure of hemoglobin
  • 1937: Krebs elucidated the citric acid cycle
  • Biochemistry has been dynamic for only about 100 years
• Living Systems Require a Limited Variety of Atoms and Molecules:

  • Only three elements (oxygen, hydrogen, and carbon) make up 98% of the atoms in any organism
  • Hydrogen and oxygen are prevalent due to the ubiquity of water
  • Carbon is uniquely suited to be a key atom of biomolecules
• The major types of biomolecules found in all types of living organisms are proteins, carbohydrates, lipids, and nucleic acids
• Biochemistry is an interdisciplinary science incorporating:

  • Organic chemistry, which describes the properties of biomolecules
  • Biophysics, which applies physics techniques to study the structures of biomolecules
  • Medical research, seeking to understand disease states in molecular terms
  • Nutrition, which describes the dietary requirements for maintenance of health
• Biochemistry draws major themes from other fields:

  • Microbiology, showing single-celled organisms and viruses are suited for elucidating metabolic pathways
  • Physiology, investigating life processes at tissue and organism levels
  • Cell biology, describing the biochemical division of labor within a cell
  • Genetics, describing mechanisms that give a cell or organism its biochemical identity
• Chemical Bonds:

  • Biomolecules interact covalently and non-covalently
  • Covalent bonds are formed by sharing a pair of electrons between adjacent atoms
  • Biomolecules also interact reversibly via non-covalent interactions like electrostatic, hydrogen bonds, and van der Waals interactions
  • Enzyme-catalyzed chemical reactions in a living organism are collectively called metabolism
• Non-covalent interactions between biomolecules are essential to life:

  • Weak, accumulatively large interactions play essential roles in many life processes
  • Types of interactions (electrostatic, hydrogen bonding, van der Waals) differ in geometry, strength, and specificity
• Atom:

  • Basic unit of matter
  • Made up of subatomic particles: protons (+), neutrons (=), electrons (-)
• Chemical Bonds:

  • Atoms in compounds are held together by chemical bonds
  • Covalent bonds are formed when electrons are shared between atoms
  • Ionic bonds are formed when electrons are transferred between atoms
  • Van der Waals forces and hydrogen bonding are also important in biomolecular interactions
• pH:

  • pH is a measure of acidity or alkalinity of a solution
  • pH scale ranges from 0 to 14
  • pH = -log[H+], where [H+] represents hydrogen ion concentration
  • Acid/Base Definitions: Acids donate protons, bases accept protons
• The Henderson-Hasselbach Equation relates pH, pKa, and the concentrations of acid and conjugate base in a buffer solution
• Buffers:

  • Solutions that resist changes in pH
  • Consist of a weak acid and its conjugate base
  • Buffer systems in body fluids include protein buffer system, hemoglobin buffer system, and carbonic acid-bicarbonate system
• Carbohydrates:

  • General characteristics include being polyhydroxy aldehydes or ketones and their derivatives
  • Composed of C, H, and O
  • Functions include being sources of energy, intermediates in biosynthesis, and forming structural tissues
• Types of Carbohydrates:

  • Monosaccharides: simple sugars with multiple OH groups
  • Disaccharides: 2 monosaccharides covalently linked
  • Oligosaccharides: a few monosaccharides covalently linked
  • Polysaccharides: polymers consisting of chains of monosaccharide or disaccharide units
• Monosaccharides:

  • Empirical formula is Cn(H2O)n
  • Can exist in open chain or ring structures
  • Multiple structural and optical isomers are possible
  • Common monosaccharides include pentoses and hexoses
• End of key information
• Monosaccharides:

  • Generally have between 3 and 6 carbon atoms
  • Most common monosaccharides are pentoses (5 carbons) and hexoses (6 carbons)
  • Monosaccharide straight chains have at least one carbonyl group C=O
  • Aldose sugars have the carbonyl group at the end, while ketose sugars have it within the chain
• Stereoisomers:

  • D and L forms are based on the configuration about the single asymmetric C in glyceraldehyde
  • Dextrorotatory (D) and levorotatory (L) refer to optical isomers
  • Most naturally occurring sugars are D isomers
• Cyclization:

  • Glucose forms an intramolecular hemiacetal as C1 aldehyde and C5 OH react to form a 6-member pyranose ring
  • Haworth projections represent cyclic sugars with essentially planar rings and OH at the anomeric C1 as a (OH below the ring) or b (OH above the ring)
• Mutarotation:

  • Anomers a and b freely interconvert in solution via the open chain form of sugar
  • Equal concentrations of D- and L-isomers form a racemic mixture (DL mixture) that does not exhibit optical activity
• Reactions of Monosaccharides:

  • Action of base on sugars can form salts at high pH and interconvert D-mannose, D-fructose, and D-glucose
  • Sugars that react with oxidizing agents are reducing sugars, forming a red precipitate with copper sulfate
  • Aldoses may be oxidized to aldonic acids or uronic acids
  • Glucose oxidase converts glucose to gluconic acid and hydrogen peroxide
  • Glucose can react with hemoglobin to form glycosylated hemoglobin (HbA1c) for monitoring blood glucose levels
• Reduction:

  • Glucose forms sorbitol, mannose forms mannitol, fructose forms a mixture of mannitol and sorbitol
  • Mannitol is used as an osmotic diuretic, glycerol is used as a humectant
• Dehydration:

  • Monosaccharides are dehydrated by strong acids to yield furfurals like furfural and 5-hydroxymethyl furfural
  • Furfurals react with -naphthol to produce a purple product, basis for the Molisch test
• Disaccharides:

  • Maltose: 2 α-D-glucose molecules joined via α(1→4) linkage
  • Lactose: β-D-galactose joined to α-D-glucose via β(1→4) linkage
  • Sucrose: α-D-glucopyranosido-β-D-fructofuranoside with a(1→b2) glycosidic bond
• Polysaccharides:

  • Homoglycans (starch, cellulose, glycogen) and heteroglycans (gums, mucopolysaccharides)
  • Starch is composed of α-amylose and amylopectin, used as a storage polysaccharide
• Formation of Glycosidic Bonds:

  • Anomeric hydroxyl groups of two sugars can join to form a glycosidic bond
  • Two glucose molecules combine to form disaccharides like maltose
• Formation of Esters:

  • Alcoholic groups of monosaccharides can be esterified by non-enzymatic or enzymatic reactions
  • ATP donates the phosphate moiety in ester formation
• Fermentation:

  • Yeast can ferment glucose, fructose, maltose, and sucrose to ultimately produce pyruvate and ethanol
• Derivatives of Monosaccharides:

  • Include sugar acids (e.g., gluconic acid), sugar alcohols (e.g., sorbitol), aldoses, amino sugars, deoxysugars, and L-ascorbic acid (vitamin C)
• Formation of Osazones:

  • Reacting monosaccharides with phenylhydrazine in acetic acid to obtain crystalline compounds
• Formation of Hemiacetal and Hemiketal:

  • An aldehyde can react with an alcohol to form a hemiacetal, while a ketone can react with an alcohol to form a hemiketal
  • Pentoses and hexoses can cyclize as the ketone or aldehyde reacts with a distal OH
• Main sources of starch are rice, corn, wheat, potatoes, and cassava
• Starch is a storage polysaccharide
• Starch is used as an excipient in medications to aid the formation of tablets