Chapter 2 - The Cell: Structure and Function|

Polar Molecules and Hydrogen Bonds
Covalent bonds result from sharing electrons. However, some atoms (O, N, S) attract electrons more and have a slight negative charge around them.
Hydrogen attracts electrons more weakly when bonded to O, N and S and has a slight positive charge.
Nonpolar bonds are covalent bonds with equal sharing of electrons. e.g. C-H.
Polar bonds are covalent bonds with unequal sharing of electrons (In other words, there are two poles in the bond, one negative and one positive). e.g. O-H, N-H, and S-H.
Hydrogen bonds result from the fact that the slight positive charge around the hydrogen atom in a polar covalent bond attracts the slight negative charge around atoms in other covalent bonds. (Remember that opposite charges attract and like charges repel one another. This is an important rule to keep in mind.)
      Water molecules form hydrogen bonds with other water molecules and with other polar covalent bonds on other molecules. This is because the oxygen atom has a stronger attraction for the electrons then the two covalently bonded H atoms. Because the hydrogen atoms are asymmetrically bonded to the oxygen atom the region around the hydrogen atoms is slightly positive and the side of the oxygen atom furthest from the hydrogen atoms has a slight negative charge. Hydrogen bonds form between the oxygen atoms and the hydrogen atoms of the water molecules. This accounts for the surface tension of water (An important concept to understand when we look at the mechanics of lung ventilation)
     This property of water is important to understand because water is the most important solvent in living systems. Molecules that are polar or that possess an electrical charge (ions) can more readily dissolve in water. These molecules are hydrophilic (water loving). Nonpolar molecules do not as readily dissolve in water and are hydrophobic (water fearing).

Ions and Ionic Bonds
Ions are atoms that gain or lose electrons completely and acquire a positive or negative charge. Positive ions are cations; negative ions are anions.
Anions and cations strongly attract one another and from crystals (e.g. NaCl table salt)
When ions are dissolved in water they are also called electrolytes because they conduct electric currents.
Body fluid contain a number of electrolytes including Na+, K+, Ca++, H+, Mg++, Cl -, SO22-, HCO- 
Molecules containing ionized groups are hydrophilic.

 

Biomolecules

Definition: Molecules synthesized by living organisms and containing carbon atoms.
Carbon is capable of forming four covalent bonds with other atoms including itself. This enables it to form complex molecules.
Oxygen, hydrogen and nitrogen are other atoms common to biomolecules.
Polymers are molecules that consist of repeated subunits. e.g. proteins (amino acids), polysaccharides (sugar)

 

Four Basic Types of Biomolecules

1.

Carbohydrates - Molecules with carbon, hydrogen and oxygen in the ratio of 1:2:1.
Presence of hydroxy groups (-OH) make carbohydrates polar and readily dissolvable in water.
             Subcategories of Carbohydrates:
Monosaccharides - Simple sugar molecules composed of only one unit. Examples:
Glucose (C6H12O6) Important source of energy in the body.
Fructose (C6H12O6)
Galactose (C6H12O6)
Ribose (C5H10O5) Important components of nucleotides
Deoxyribose (C5H10O4)
Disaccharides - Two monosaccharides joined by a covalent bond.
Sucrose Glucose and Fructose (table sugar)
Lactose Glucose and Galactose. Sugar found in milk (remember terms such as lactation and the hormone prolactin.
Polysaccarides - Two monosaccharides joined by a covalent bond.
Glycogen Polymer of glucose subunits. Storage form of carbohydrates in animal cells.
Starch Polymer of glucose subunits. Storage form of carbohydrates found in plants.
Cellulose Polymer of glucose subunits  Indigestible polysaccharide that forms dietary fiber..

 

2.

Lipids - Contain primarily carbon and hydrogen atoms linked by nonpolar bonds.
However, lipid molecules may also contain oxygen and phosphate groups (HPO4-) that create polar regions. When a molecule contains both polar and nonpolar regions it is described as amphipathic (amphi (both) pathos (feeling)).
     Four Classes of Lipids:
Triglycerides (Fat)
Composed of two components:
     One glycerol (3 carbon alcohol)
     Three fatty acids (long chain of hydrocarbons with -COOH at one end. Most have an even number of carbons, commonly 16 or 18.
Saturated fatty acids - contain carbon atoms linked only by single bonds.
Unsaturated fatty acids - have one or more carbons linked by double bonds.
     monounsaturated - fatty acid contains one double-bonded pair of carbons.
     polyunsaturated - fatty acid contains more than one double-bonded pair of carbons.
Phospholipids
     Lipids that contain a phosphate group. Similar in structure to a triglyceride except that the third carbon of the glycerol is bonded to a phosphate group. Phospholipids are amphipathic because two fatty acids (tails) are nonpolar while the phosphate group that is invariably attached to another chemical group (head) is polar.
Phospholipids give rise to two structures when placed in water:
Phospholipid bilayer - forms the core of cell membranes
Micelles - spheres whose inner nonpolar region can function to transport nonpolar substances in water.
Eicosanoids
    Derived from a 20 carbon fatty acid that folds upon itself and forms a 5 carbon ring in the middle. Examples include prostaglandins, thromboxanes and leukotrienes.
Steriods
     Molecules with a unique three 6 carbon rings and one five carbon ring structure
     Cholesterol is an important lipid component of the cell membrane. Slightly amphipathic because of -OH attached at one end. Cholesterol is a precursor to a number of steroid hormones including testosterone, estradiol, cortisol and calcitriol.

 

3.

Proteins - Proteins are polymers (poly (many) meres (parts)) of amino acids.
Amino acids consist of a central C atom attached to an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom and a residual group. Residual refers to what "resides" in the molecule after the key identifying groups are accounted.
Twenty different residual groups, or 20 different amino acids, are important in humans. These amino acids function as components of proteins and in intercellular communication.
Amino acids become covalently bonded to one another when the amino group of one reacts with the carboxyl group of another in a reaction that releases a water molecule. The reaction is called a condensation reaction and the bond is called a peptide bond. The resulting polymer is a polypeptide.
Generally speaking, peptides consist of a chain of less than 50 amino acids while proteins are chains of more than 50 amino acids.
The essence of protein function resides in its complex three dimensional structure or conformation. The complexity of protein structure is separated into four levels, primary, secondary, tertiary and quaternary. (In other words, 1st, 2nd, 3rd and 4th levels).
Primary protein structure simply refers to the sequence of amino acids.
Secondary protein structure results from the hydrogen bonds that form between the amino and carboxyl groups of the amino acids in the chain. As a result of these hydrogen bonds the polypeptides may form shapes such as  alpha helices and beta pleated sheets.
Tertiary protein structure results from the interactions between the R-groups of different amino acids in the same polypeptide. The interactions that result in this tertiary structure include:
a. hydrogen bonds
b. ionic bonds
c. van der Waals forces
d. covalent bonds (e.g. disulfide bonds between cysteine amino acids)
Quaternary protein structure is found only in proteins with more than one polypeptide chain, e.g. hemoglobin consists of four separate polypeptide chains.
Proteins can be classified as either fibrous or globular based on their three dimensional conformation.
     Fibrous proteins form elongated strands that serve a structural or motile function, e.g. collagen.
     Globular proteins are coiled, folded and more compact. These function as chemical messengers, receptors, carrier proteins and enzymes.
Proteins are also classified as glycoproteins when carbohydrates are attached and lipoproteins when lipids are attached.

 

4.

Nucleotides and Nucleic Acids
Nucleotides contain:
   1. One or more phosphate groups
   2. Five carbon carbohydrate (ribose or deoxyribose)
   3. Nitrogenous base:

a.

pyrimidine - cytosine, thymine or uracil

b.

purine - adenine, guanine
Cyclic nucleotides result from a covalent bond that forms between the O of a phosphate group and the third carbon (C3) of the carbohydrate group. Notable examples are cyclic AMP and cyclic GMP.
Nucleic Acids are polymers of nucleotides
   deoxyribonucleic acid (DNA)
   ribonucleic acid (RNA)
Both are involved in the storage and expression of genetic information.
DNA has deoxyribose as its carbohydrate and four base:
   adenine  (A)
   thymine  (T)
   cytosine  (C)
   guanine  (G)
DNA consists of two strands of nucleotides held together in a double helix by hydrogen bonds by complementary base pairing.
Law of complementary base pairing:
   G of one strand pairs with the C of other strand (G-C).
   A is always paired with T (in RNA A is paired with U)
RNA has ribose as a carbohydrate and four bases:
   adenine (A)
   uracil  (U) instead of thymine
   cytosine (C)
   guanine  (G)
RNA is synthesized from DNA by complementary base pairing with
  A - U,  T - A,  G - C,  C - G

 

Protein Synthesis
Genetic Code
   A gene consists of a sequence of bases in DNA that codes for a particular protein or RNA molecule. The code consists of a sequence of triplets of three bases. Four bases can be arranged in 64 permutations (43 = 64) of 64 different codes. These triplets are converted to sequences of three base pairs on messenger RNA called codons. The codons are converted to polypeptides consisting of 20 different amino acids.
Transcription
   The information contained in a strand of DNA is transcribed onto a strand of RNA. Complementary base pairing results in the G on the DNA becoming an C on RNA; the A becomes a U; the T becomes an A; the C becomes a G. (Fig. 2.28)
   Transcription begins when the enzyme RNA polymerase identifies a sequence on the DNA called the promoter sequence. RNA polymerase causes the two strands of DNA to separate and initiates the transcription of the base sequence. Free ribonucleotides ATP, UTP, GTP and CTP pair up on the bases of DNA according to complementary base pairing. RNA polymerase catalyzes the bonding of the RNA nucleotides to from a polynucleotide. (Fig. 2.29)
   Transcription of DNA results in three kinds of RNA

1.

Messenger RNA (mRNA)

2.

Ribosomal RNA (rRNA)

3.

Transfer RNA (tRNA)
   mRNA undergoes post-transcription processing. Regions of excess bases called introns are removed from the transcribed mRNA and the remaining bases called exons are spliced together. A chemical group called a "cap" is added to the 5' end and adenine nucleotides are added to the 3' end to from a poly A tail. The processed mRNA is then transported through the nuclear pore into the cytoplasm. (Fig. 2.30)
Translation
   Occurs in association with ribosomes in the cytoplasm. Ribosomes are where mRNA and tRNA align. tRNA binds a specific amino acid at its 3' end and has a region in it's cloverleaf shape that contains an anticodon. The anticodon binds to the appropriate codon on the mRNA.(Fig. 2.31)
   Translation begins when initiation factors, the small subunit of rRNA, and a charged tRNA with an anticodon complementary to the initiation codon AUG (methionine) are alligned correctly on the initiation codon of mRNA. The large subunit then displaces the initiation factors and the initiation tRNA is correctly alligned in the P site of the ribosome. (Fig. 2.32)
   A second charged tRNA with an anticodon for the next codon enters the A site of the ribosome. An enzyme in the ribosome catalyzes the formation of a peptide bond between the amino acids. The first amino acid (always methionine) is released and the tRNA is released from the ribosome. The ribosome then moves to the next codon moving the second tRNA into the P site while the appropriate tRNA with its amino acid moves into the A site.(Fig. 2.33)
   The process of peptide bond formation; release of free tRNA from the P site; movement of rRNA to the next codon on mRNA is repeated until the termination codon is reached. The polypeptide is released and the ribosome and mRNA disassociate.
Destination of Proteins
   The destination of proteins is determined when a leader sequence is translated. The leader sequence interacts with other proteins in the cell to determine its ultimate destination. Possible destinations include the nucleus, mitochondrion and peroxisome. (Fig. 2.34)
   If the protein is destined for the endoplasmic reticulum the leader sequence binds to the signal recognition protein in the membrane of the endoplasmic reticulum and and the protein undergoes post-translational processing. 
 Post-translational Processing
   This includes cleavage of amino acids (e.g. leader sequence) and addition of molecules including lipids and carbohydrates (glycosylation). Post-translational processing may occur in the rough endoplasmic reticulum, Golgi apparatus and after packaging by the Golgi apparatus.
   If the protein is to undergo further processing in the Golgi apparatus it is packaged into a transport vescicle that detaches from the smooth endoplasmic reticulum and travels to the cis- (side closest to the er) cisterna of the Golgi apparatus. The protein is processed as it travels from the cis-cisterna to the trans-cisterna (side furthest away from the er). The Golgi apparatus sorts and packages proteins into vesicles that determine their ultimate destination. (Fig. 2.35)

 

Regulation of Protein Synthesis
Regulation of Transcription
   Transcription typically is regulated at the point when RNA polymerase binds to the promoter sequence of DNA. Transcription can be induced (turned on) or repressed (turned off) depending upon the cells' need for the protein.
Regulation of Translation
   Translation can be regulated at the initiation phase by mechanisms that remain poorly understood.
Protein Degradation
        Proteins are degraded by proteins called proteases. Proteins can be tagged for destruction by a polypeptide called ubiquitin that directs the protein to a protein complex with proteases called proteosome..