CH 105 - Chemistry and Society

Ethanol: Biochemistry

03/10/2007

Science, Atoms, and Molecules

• Ethanol is a molecule (the smallest particle of a compound that possesses the chemical properties of the compound; a definite, distinct, electrically neutral group of bonded atoms) that consists of carbon, oxygen and hydrogen atoms. These atoms are nonmetals. 
• Our experience from the alcohol industry tells us that ethanol is soluble in water, since two distinct phases are not seen when ethanol is mixed with water as is observed when oil and water are mixed.  A quick demonstration shows that it evaporates more readily than water.  A solution (homogeneous mixture) of water and ethanol can be separated by distillation, in which the mixture is heated.  The ethanol evaporates more readily and can then be collected in the liquid form by condensation on a cold surface (such as a glass tube with cold water running through it).

Bonding

• It is held together by covalent bonds involving the sharing of electrons between the bonded atoms.  (insert Lewis structure). 

• In the Lewis structure, the carbon and oxygen atoms are surrounded by eight electrons (an octet of electrons, or four pairs), leading to the stability of these atoms in comparison to atomic C and O which have 4 and 6 outer shell electrons respectively.  (C is in group 4 and oxygen in group 6 of the periodic table.)  H has a duet of electrons.  Since these atoms are nonmetals, they achieved filled outer shell through the sharing of electrons.
• There are two types of bonds in ethanol. The C-H bonds are nonpolar covalent, since these atoms are of similar electronegativity  (the ability of an atom to attract electrons to itself when it is bonded to another atom in a compound.)  The C-O and O-H bonds are polar covalent since O is significantly more electronegative than either C or H.  Hence there is a slight + charge (d+) on the C and H attached to the O and a slight - charge (d-) on the O.
• The formal charge on each atom in ethanol is zero.  This is calculated by assigning electrons to each atom in ethanol and comparing the number assigned each atom to the number found in the outer shell of the lone atom unbonded.  Lone pairs are assigned to the atom they are placed around in the Lewis structure.  Bonded electrons are divided equally between the two atoms in the bond.  If atom in a molecule are assigned more electrons than the lone atoms has in its outer shell, it would have negative charge equal to the excess number of electrons.  Positive charges develop when they are assigned fewer.
• With 8 electrons (4 pairs) surrounding the C and O of ethanol, the geometry of the electrons clouds around the C and O  are tetrahedral, with bond angles of approximately 109^o.  In this arrangement, the electrons clouds, which repel each other, are as far apart as possible.  Since 4 atom are attached to each carbon, the geometry of the atoms around the C is also tetrahedral.  However, only two atoms (C and H) are attached to the O, so the geometry of the atoms around the O is bent or angular.  This geometry shows that their is a separation of the center of slight positive and slight negative in the molecule, which makes this molecule polar.

Intermolecular Forces and Solutions

• Ethanol is a liquid at room temperature, implying that ethanol molecules can attract other ethanol molecules with strong enough intermolecular forces that the substance remains a liquid at room temperature. Part of ethanol (CH₃CH₂- is nonpolar and might be thought to make ethanol insoluble in water.  However, the C and H directly bonded to O are slightly charged, making this end of the molecule polar.  As mentioned above, the molecule, given its small size, is polar.  This property makes water soluble in water.  Its nonpolar part does also contribute to its solubility in nonpolar substances such as gasoline (in gasohol).  I'm not certain if additive are required to increase it solubility in nonpolar gasoline.
• ethanol molecules can attract other ethanol molecule and water through H bonds.  The nonpolar ends of ethanol would attract nonpolar molecules such as those found in gasoline through induced dipole - induced dipole interactions (London forces).  

Chemical reactions

• Ethanol can participate in redox reaction with a variety of oxidizing agents.  It can be burned (combustion reaction) with O₂ (g) in a redox reaction which produces CO₂(g) and H₂O(g).  In this case oxygen gas serves as the oxidizing agent (causes ethanol to lose electrons).  O₂ (g) is then reduced.   This loss (oxidation) and gain (reduction) of electrons can be mostly readily determined by calculating the oxidation number for each atom in the molecules.  Oxidation number represent another way to count the electrons around atoms in molecules and ions (sort of another kind of charge).  The are calculated in the same way as formal charge (described above) only bonded electrons (shared pairs) are given entirely to the more electronegative atom (usually F, O, or N) in the bonded pair.  If two identical atoms are bonded together, the electrons in bond between them are divided equally between the two identical atoms.  Oxidation of ethanol with O₂ can be used to produce energy to drive vehicles or to power our muscles when we drink it.
• Ethanol can participate in acid/base reactions under some conditions.  The H attached to O in ethanol is slightly positive and could be attacked by a strong base which abstracts the proton from the OH group on ethanol, leaving a negative on the electronegative O.  Since the O is electronegative, and tends to pull electrons toward it, this negative on O makes this product somewhat stable.  However, compare the acidity of ethanol to another two carbon molecule, acetic acid.  It can give up a proton on the OH to form acetate.  In this case, the negative on the O can be "diluted" through a process called resonance so that it is distributed over both Os on the acetate ion.  This results in a lower negative charge density in the acetate, making it more stable than the negative ion resulting for ethanol acting as an acid.  Hence acetic acid (which is a weak acid, and weak electrolyte) is a much stronger acid than ethanol and we don't consider ethanol as an acid.

Cells and Signal Transduction

• Ethanol potentiates Cl- in flow through GABA A channels, making the neuron more refractory to activation (i.e the neuron is hyperpolarized by making the transmembrane potential more negative). Hence it inhibits neuron firing.
• Ethanol inhibits one type of glutamate excitatory neurotransmitter channels, the N-methyl-D-aspartate channel.  It binds to a different site on the channel than does glutamate. (JBC, 49, pp 48815, 2003)
• Ethanol appears to activate cAMP pathways in neurons. as well. 
• In addition, it activates K+ channels, promoting efflux of K+ ions and making the transmembrane potential more negative, inhibiting neural firing. (Cell, 115, pg 655, 2003)

Organic Chemistry

• Ethanol is an example of an organic molecule containing the alcohol functional group, ROH.  Other common functional groups include aldehydes, ketones, amines, carboxylic acids, and carboxylic acid derivatives including anhydrides, esters, and amides.
• Direct oxidation (burning) of ethanol by oxygen to produce carbon dioxide and water is a fairly uncontrolled reaction that produces much energy.  The oxidation process can be controlled more readily and produced smaller increments of energy loss when other oxidizing agents are used.  In the lab, CrO₃ can be used to oxidize alcohols like ethanol acetaldehyde, which can be further oxidized to acetic acid.

Biochemical Structures

• Ethanol is metabolized in the body using a different oxidizing agent, NAD⁺, to produce acetaldehyde.  This reaction is catalyzed by the enzyme alcohol dehydrogenase (ADH). There are 5 different versions of ADH in the body.  Two of these, which convert ethanol very quickly to acetaldehyde, are found often in Asians.  The quick generation of the toxic acetaldehyde produce unpleasant symptoms which probably contribute to the decreased use of ethanol in Asian cultures.

• acetaldehyde is further oxidized to acetic acid in a reaction catalyzed by another enzyme, acetaldehyde dehydrogenase found in the liver.  There are two different forms of the enzyme, one found in the cytoplasm of the cell and the other in the mitochondria.  Half of all Asian people do not have a function form of the liver enzyme, which leads to increased cellular levels of the toxic acetaldehyde and a noticeable flushing in the skin.    .

Central Dogma Biology

• Ethanol alters gene expression in target cells, similar to other addicting drugs.  We saw that such drugs affect the reward centers of the brain, mediated by the ventral tegmental area (VTA) and the nuclear accumbens (NA).  VTA activation causes dopamine release at the NA neuron.  One effect of this is activation of cellular adenylate cyclase which increases intracellular levels of the second messenger molecule cAMP.  Hence the dopamine receptor, of which there are at least five types, are not neurotransmitter-gated ion channels.  Rather on binding to dopamine and subsequent shape changes, the receptor binds to and activates adenylate cyclase, which makes cyclic AMP (cAMP).  The interaction between the receptor and adenylate cyclase is mediated by a G protein (so named since it binds GTP).  The cAMP second messenger activates Protein Kinase A which transfers a phosphate from ATP to many proteins, including the cAMP Response Element Binding Protein (CREB), a transcription factor.  When phosphorylated this protein is activated binds to the cAMP response element (CRE) upstream from certain genes, which are then transcribed.  One is dynorphin, a morphine-like molecule, which acts to inhibit firing (and hence release of dopamine) from VTA cells at the vTA-NA synapse.  This reduction in dopamine elicits a response (tolerance, craving, dependence) that causes increased drug use to get the same psychological effects. 
• Another protein transcription factor in the NA neuron, delta-fosB, is activated by phosphorylation through the same pathway.  This protein is more stable and stays active in neurons weeks after drug use has stopped.  It can alter gene transcription in a long term sense, and may account for sensitization responses for drug use, when lower amounts of drugs and a variety of social and environmental cues can lead to "falling off the wagon".   
• http://www.jneurosci.org/cgi/content/full/19/9/3277?ck=nck

Stoichiometry