Week 1

  • Atomic Structure
    • Atoms start off with the same number of protons and electrons
    • In this way, atoms start off with a neutral charge
    • But once they start forming new bonds with other atoms, things change
  • Chemical Bonding
    • Bonds between atoms are formed by sharing electrons
    • But this sharing isn't always equal
    • Some atoms pull the electrons closer to their own nucleus meaning they get more (or all) of the electron, and its associated charge.
  • Electronegativity
    • Upper right of the periodic table has high electronegativity.
    • Highly electronegative elements are highly reactive because of their strong tendency to capture electrons.
    • Low electronegative elements are highly reactive because they yield electrons easily.
    • Carbon
    • Is special
    • It is like a scaffold
      • Carbon can make 4 bonds
      • Carbon isn't very electronegative, so the bonds are usually covalent and stable
  • What does the type of bond mean for some common molecules
    • Non polar covalent bonds are hydrophobic-avoid water
    • Polar covalent bonds are hydrophilic- likes water
  • Hydrogen bonding
    • Hydrogen bonding in water is an example of polar molecules forming a weak bond with each other based on their polar charges.
    • This attraction can be so strong that it forces nonpolar molecules together.
    • Hydrogen bonding is critical when we start to think about physiology and biochemistry.
  • Major classes of molecules in Biochemistry?
    • Proteins
    • Are made up of amino acids
    • Amino acids all have a similar structure, with different side chains
    • Proteins contain nitrogen in addition to carbon, hydrogen and oxygen
    • Carbohydrates
    • Consist of carbon, hydrogen, and oxygen molecules
    • There are simple sugars such as sucrose and lactose (these are disaccharides), and starch, which is a polysaccharide
    • Lipids
    • Lipids or fats are composed of fatty acids and glycerol
    • They contain less oxygen than carbohydrates or proteins
    • Nucleic Acids
    • Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) are polymers made up f nucleotides
    • Nucleotides consist of a sugar (carbohydrate) with a base (nitrogen-containing molecule) and phosphate molecule attached
    • These structures are important for understanding how genetic information is passed from one cell to another.

Water, Acids, Bases, and Buffers

  • Water

    • Water is a solvent of life
    • It performs many functions including
    • Dissolves and transports molecules
    • It is a component of many chemical reactions
    • It helps dissipate heat and control of body temperature
    • Body water remains relatively constant at about 60% of our weight
    • Adipose tissue contains little water, so individuals who have more adipose tissue may have relatively less body water

  • Fluid compartments

    • Compartmentalization helps our body's control the relative concentration of molecules
    • This increases the probability that certain reactions will occur and helps maintain homeostasis
    • Water can move between compartments and because it is the solvent in the body, it can impact concentrations.

  • Why is water a solvent

    • The shared electrons of H-O bond are not shared equally, they spend more time near the oxygen nucleus
    • This gives the hydrogen atoms a partial positive charge
    • It also gives the oxygen atom partial negative charge
    • The polarity of water allows polar molecules to dissolve
    • Hydrogen bonds formed with polar compounds and 'hydration shells' surround ions
    • Hydrogen bonds are weak, constantly breaking and reforming, so that solutes can move in solution and water can move through pores in cell membranes.

  • Electrolytes and Osmolarity

    • Water dissolves many anions (Cl-, HCO3, P04^2-) and cations (K+, Na+)- these are collectively termed electrolytes
    • Osmolarity is the concentration of all dissolved solutes in the blood (electrolytes, proteins, etc.)
    • Because Water is small, dissolves solutes and is to move between compartments water will keep the osmolarity the same (remember osmosis)
    • Water will move to the higher concentration of solutes to equalize it.

  • Water and pH

    • Water itself is in equilibrium
    • pH is a measure of the acidity or alkalinity of a solution
    • In other words, how many hydrogen ions are in the solution.
    • Blood has many electrolytes, acids, bases, and many other molecules dissolved in it, therefore the pH of blood doesn’t match water,
    • Blood pH is normally between 7.35-7.45
    • >7.45 = basic/alkaline

  • Acids and Bases

    • Acids are molecules which can release or donate H+ to a solution
    • Bases are molecules which can accept an H- (e.g., OH-)
    • Strong acids are much more electronegative and are therefore much more pull the electron completely away from hydrogen, releasing it.
    • Weak acids are less electronegative and less likely to completely dissociate.
    • Weak acids(HA) dissociate into H+ and conjugate base (A-)
    • The tendency to dissociate is defined by the equilibrium constant, Ka
    • Ha
    • Ka = [H+] [A-] / [HA]
    • The larger the Ka, the greater the tendency to dissociate
    • Henderson-Hasselbalch Equation
    • pH = pKa + log [A-] / [HA]
    • When the pH = pKa, 50% of the acid is dissociated
    • For buffers, this is when a buffer is most effective, although it is still useful at +1 pH unit of the pKa.

  • Buffers

    • Buffers are combinations of weak acids and their conjugate base
    • Buffers resist changes in pH, they are most effective when pH=pKa, because equal amounts of both acid and base are present
    • Because both acid and base are present, protons can be accepted and donated to maintain pH.
    • Buffering is critical to how our body maintains pH in the blood, cell, fluids, tissues, everywhere.
    • Biologically important buffers
    • Metabolism produces large quantities of acid each day
    • There are several buffering systems in the body to deal with the metabolic acids produced
    • The dihydrogen phosphate-hydrogen phosphate (H2P04-
    • Hemoglobin has an amino acid chain that can accept H+, there are other proteins in cells that can do this as well.
    • Carbonic Acid- Bicarbonate buffer system
      • The carbonic acid- bicarbonate equilibrium is the major buffering system in the blood
      • The Ph of blood would drop dramatically if not for this system
      • Th carbon dioxide (CO2) produced from fuel metabolism is the major source of acid, and its buffer.

  • Red blood cells play a critical role in regulating blood pH

  • Questions

    • Acidic because the pH is less than 7.35. .
    • They indicate that there is more respirations to get the CO2 out, as a result of the reaction going to the reverse direction.
    • Basic

  • Respiratory vs Metabolic causes of pH imbalance.

Biologic Functional Groups

  • Carbon molecules

    • Carbon can make 4 bonds
    • Single or double bonds between C's form the backbone of many molecules
    • The "ane" suffix denotes single bonds, while "ene" denotes double
    • The "yl" implies that it is a group attached to a compound.
    • "iso" is a prefix when 2 carbons are bonded to another carbon, forming a branch which is an isomer of the straight chain compound.
    • If the compound is a straight chain, it is called aliphatic
    • If the compound is a ring, it is called cyclic and usually has the prefix "cyclo", however.
    • Compounds containing the 6 carbon benzene ring are special
    • The compounds are referred to as aromatic
    • The electrons are shared equally in these hydrocarbon structures, so they are non-polar(and not very reactive)

  • Labeling Carbons

    • Carbons in a molecule can be numbered, with carbon-1 being the carbon in the molecule that
    • Another other method uses Greek letters to count starting from the carbon next to the most oxidized Carbon
    • This molecule can be called 3-hydroxybutyrate of (beta)β-hydroxybutyrate

  • Functional Groups

    • Carbon and Hydrogen share electrons equally, forming a covalent bonds
    • This means that Carbon-Hydrogen bonds are very stable, great form making a structure, not so great for reacting with other compounds.
    • Functional groups are bonded to the carbon chain
    • They are usually between carbon and oxygen, nitrogen, sulfur, or phosphate groups
    • They tend to be polar (most of those groups are more electronegative than C) and more reactive.

  • Electronegativity

    • Oxygen, Nitrogen and sulfur are all electronegative than Carbon
    • Like water, they form polar bonds, where the electrons spend more time around the O, N, or S.
    • Because of the polarity of the binds, substance with groups containing these elements are more hydrophilic (water-liking)
    • Partial positive charges on carbon molecules attract negatively charged groups and make reactions likely.

  • Oxidized vs Reduced Groups

    • C-C groups and C-O groups are 'oxidized' or 'reduced' depending on the electrons around the carbon atom
    • Loss of electrons (loss of H or gain of O) is oxidation
    • Gain of electrons (gain of H or loss of O) is reduction
    • Mnemonic to remember : LEO the Lion says GER

  • Charged Groups- Acids

    • Acidic groups, such as those shown to the right dissociate at physiological pH and exist as anions
    • Carboxylic acids are weak acids, they have a conjugate base that exists in equilibrium with the acid.
    • Phosphoric acid is H3PO4, on proton is lost at low pH, but:
    • This equilibrium has a pKa of 6.8
    • What does that mean physiologically.

  • Charged Groups- phosphate

    • Phosphate is a very important and common functional group
    • It is so common that it is usually just abbreviated by P. For example, glucose 6-P
    • Does a phosphate group make a molecule more or less water soluble (and hydrophilic or hydrophobic)

  • Charged groups- Amines

    • Compounds with nitrogen are usually basic at physiological pH and can have a positive charge
    • If nitrogen has 3 bonds there is no charge on the molecule (e.g. NH3)
    • There are 2 remaining electrons in nitrogen's valence shell, if they form a bond with a carbon atom or hydrogen ion, the N has a positive charge.

  • Esters and Amides

    • Esters and amides are formed through condensation reactions
    • If a water molecule is lost, it is a condensation reaction
    • They can be broken down using water as well (hydrolysis reactions)
    • CO2 is the anhydride form of carbonic acid H2CO3(so a molecule of water has been removed)

  • Carbohydrates

    • Monosaccharides have 3 or more carbon atoms, with a ketone or aldehyde group and hydroxyl groups
    • General structure of :
    • For example- fructose and glucose which are both C6H12O6
    • Fructose is a ketose and glucose is an aldose, notice that both end in "ose", the suffix for a sugar.

  • D- and L- Sugars

    • Sugars with chiral centre (4 different groups attached to the carbon) are designated either D- or L-
    • They are non-superimposable mirror images of each other, named for whether the 0H farthest from the carbonyl group is the same as D- or L- glyceraldehyde
    • Most sugars in human tissues are D- sugars, as opposed to amino acids proteins are only composed of L- amino acids.

  • Ring structures

    • The ring structures at bottom are the most common form of monosaccharides in solution
    • The carbonyl carbon (the one with the C=O bond) reacts with a hydroxyl group in the same molecule
    • The oxygen from the hydroxyl group becomes part of the 5 or 6 C-ring and the carbonyl carbon then has an OH group attached and is 'anomeric'.

  • Anomers of Cyclic Glucose

    • These exist in equilibrium with the straight chain form in solution
    • The OH group on the anomeric carbon can react with an -OH or an -NH group on another molecule.
    • These are glycosidic binds and can be alpha(Aa) or beta(B)

  • Amino Acids

    • Molecules that contain an amino group and a carboxylic acid group
    • Major building block of proteins
    • L-amino acids are used in proteins in living organisms
    • Do you think they are polar or non-polar?

  • Nucleic Acids

    • Nitrogen- containing ring structures
    • Can readily form hydrogen-bonds and accept or donate electrons as part of a ring
    • Form the bases of DNA, RNA and energy storage

  • Lipids- Fatty Acids

    • Lipids are made up of long chains of hydrogen and carbon with an acidic head
    • They can be saturated, meaning the maximum number of hydrogens, or unsaturated, meaning they contain one or more C=C bonds
    • They are labeled like other carbon containing molecules starting with most oxidized carbon
    • The position of the last double bond helps categorize the fatty acid.

  • Lipids-Triglycerides

    • Triglycerides, also known as triglycerols consist of glycerol and 3 fatty acids
    • The fatty acids attached to glycerol are usually different
    • The fatty acids are joined to glycerol through ester linkages and preference is shown for unsaturated fatty acids in position 2

  • Lipids-Cholesterol

    • Cholesterol is the precursor to steroid hormones in humans
    • Is it hydrophilic or hydrophobic?

  • Free Radicals

    • Free radicals, have a single electron and exist in a solution (or lipid environment) independently.
    • Many compounds in the body can be turned into free radicals when one of their electrons is removed
    • Radiation can also create free radicals
    • Oxygen free radicals, ROS, discussed in future lectures.