Class 3 Chemical Components of Cells

Chemical Components of Cells

Molecules in Cells

Cells are composed of various molecules.
The primary elements found in cells.
The process of molecular construction within cells.
Interactions within and between macromolecules.

Composition of a Bacterial Cell

Approximate composition:
- Water: 70%
- Chemicals: 30%
  - Inorganic ions, small molecules: 4%
  - Phospholipid: 2%
  - DNA: 1%
  - RNA: 6%
  - Protein: 15%
  - Polysaccharide: 2%
The composition of an animal cell is similar.
Nucleic acids make up about 6%.

Abundance of Elements

Four elements (highlighted in red) make up 99% of the total number of atoms in the human body and ~96% of our total weight.
Seven elements (highlighted in blue) represent ~0.9% of our total number of atoms.
Elements shown in green are required in trace amounts.
Molecules in cells are dominated by lighter elements.

Prevalence of Specific Atoms

Cells are made of relatively few types of atoms.
Hydrogen and oxygen are prevalent because cells are ~70% water.
Carbon is uniquely suited as a key atom of biomolecules.
Nitrogen is abundant in proteins and nucleic acids.

Electron Configuration

Elements in living organisms often have incomplete outermost shells.
Electrons in these incomplete shells can participate in chemical reactions.

Importance of Carbon

Carbon-carbon bonds form a stable backbone for molecules with strong bonds, enabling the construction of large molecules.
More energy is released when C-C bonds are combusted compared to silicon reacting with $O_2$ .
While silicon (Si) is more abundant in the Earth’s crust and can form 4 covalent bonds, C-C bonds are significantly stronger than Si-Si bonds.

Properties of Carbon Molecules

Carbon molecules are soluble in $H2O$ (cells are ~70% $H2O$ ).
They can exist as a gas and in circulation.
They are exchanged between organisms through respiration and photosynthesis.
Combustion byproduct: $CO_2$ .
Silicon, unlike carbon, is essentially insoluble after reacting with $O_2$ and remains permanently out of circulation.
Quartz is a common form of $SiO_2$ .

Essential Elements

Nitrogen (N), phosphorus (P), and sulfur (S) are also essential.
Trace elements like iron (Fe), zinc (Zn), and manganese (Mn) are vital for many life processes.
Example: Iron (Fe) is present in hemoglobin in red blood cells.

Chemistry of Cells

Based overwhelmingly on carbon compounds.
Reactions take place almost exclusively in an aqueous environment.

Water as a Solvent

$H_2O$ molecules are attracted to positive or negative charges of ions.
They dissolve in the aqueous environment of the cell (hydrophilic).
Small polar molecules also dissolve in the aqueous environment of the cell.

Macromolecule Formation

Small molecules:
- Sugars
- Fatty acids
- Amino acids
- Nucleotides
Macromolecules:
- Polysaccharides, glycogen, and starch (in plants)
- Fats and membrane lipids
- Proteins
- Nucleic acids
Macromolecules are built from subunits through the removal of water ( $H_2O$ ).
Example:
- Sugar to polysaccharide
- Amino acid to protein
- Nucleotide to nucleic acid

Major Organic Molecules

Cells contain four major families of organic molecules.
Small organic building blocks of the cell:
1. Sugars
2. Fatty acids
3. Amino acids
4. Nucleotides
Larger organic molecules of the cell:
- Polysaccharides, glycogen, and starch (in plants)
- Fats and membrane lipids
- Proteins
- Nucleic acids

Sugars

Sugars are both energy sources and subunits of polysaccharides.
In aqueous solutions, sugars are usually in cyclic form.
Examples: glycogen with branch points

Fatty Acids

Fatty acid chains are components of cell membranes.
One fatty acid tail.
Two fatty acid tails in phospholipid molecule.
Kink in chain from double bond.

Triacylglycerol Molecules

Fatty acid chains are also components of triacylglycerol molecules.
Electron micrograph of an adipocyte shows a small band of cytoplasm surrounding a large deposit of triacylglycerols.

Amino Acids

Amino acids are the subunits of proteins.
Structure:
- N-terminus (amino group)
- α-carbon (with side chain R)
- Carboxyl group (C-terminus)
Amino acid at pH 7 exists in ionized form.
Proteins make up half the dry mass of a cell.
Examples of amino acids and their side chains (R):
- Phenylalanine (Phe): $-H-C-CH_2$
- Serine (Ser): $-H-C-CH_2-OH$
- Glutamic acid (Glu): $-H-C-CH2-CH2-C$
- Lysine (Lys): $-H-C-CH2-CH2-CH2-CH2-N-H^+$

Nucleotides

Nucleotides are subunits of nucleic acids (DNA and RNA).
Components:
- Phosphate
- Sugar (ribose or deoxyribose)
- Base (A, T, G, C, or U)
5' and 3' ends.

Nucleoside Phosphates

Nucleoside di- and tri-phosphates carry chemical energy in their phosphoanhydride bonds.
Nucleotides also:
- Combine with other groups to form coenzymes (e.g., coenzyme A).
- Are used as small intracellular signaling molecules (cyclic AMP).

Covalent Bonds

Macromolecules built from covalent bonds.
Atoms share electrons to form a molecule.

Strength of Chemical Bonds

Covalent bonds are strong enough to survive conditions inside cells.
Table showing bond length and strength (kJ/mole) in vacuum and water:
- Covalent: 0.10 nm, 377 kJ/mole
- Ionic bond: 0.25 nm, 335 kJ/mole in vacuum, 12.6 kJ/mole in water
- Hydrogen bond: 0.17 nm, 16.7 kJ/mole in vacuum, 4.2 kJ/mole in water
- Van der Waals attraction: 0.35 nm, 0.4 kJ/mole

Cytosol

Cytosol is crowded.
Movement of molecules is rapid.

Covalent Bonds in Cells

Typical covalent bonds are stronger than thermal energies within the cell by a factor of 100, making them resistant to being pulled apart by thermal motions.
In cells, covalent bonds are normally broken only during specific chemical reactions controlled by enzymes.

Formation and Breakdown of Macromolecules

Large polymeric macromolecules are formed from subunits via condensation reactions (energetically unfavorable).
They are broken down by hydrolysis (energetically favorable).
Condensation and hydrolysis are reverse reactions.

Condensation and Hydrolysis

Condensation: two monosaccharides linked by a covalent glycosidic bond to form a disaccharide with water expelled.
Hydrolysis: water consumed to break the glycosidic bond in a disaccharide, forming two monosaccharides.

Peptide Bond Formation

Condensation reaction: two amino acids linked by a covalent peptide bond to form a dipeptide.
Proteins are long polymers of amino acids linked by covalent peptide bonds.
Peptides usually contain less than 50 amino acids.

Phosphodiester Linkage

Nucleotides are joined together by covalent bonds.
A 3’, 5’- phosphodiester linkage is formed between the 3’ and 5’ carbon atoms of adjacent sugar rings (ribose example).

Macromolecule Sequences

For proteins, nucleic acids, and some polysaccharides, each macromolecule contains a specific sequence of subunits.
20 amino acids: If a protein chain is 200 amino acids long, there are $20^{200}$ possible combinations.
4 nucleotides: If a DNA molecule is 10,000 nucleotides long, there are $4^{10,000}$ possible combinations.

Debate on Macromolecules

Early 20th-century debate among chemists:
- Were proteins, polysaccharides, and other large organic molecules discrete particles made of many covalently linked atoms?
- Or were they loose aggregations of heterogeneous small organic molecules held together by weak forces?

Molecular Weight Determination

Hemoglobin molecular weight = 68,000 daltons.
One dalton is nearly equal to the mass of a hydrogen atom = 1 g/mol.

Svedberg's Ultracentrifuge

Svedberg’s invention and work with the ultracentrifuge settled the debate about whether macromolecules exist.
If a protein were an aggregate of smaller molecules, it would appear as a smear of molecules of different sizes when sedimented in an ultracentrifuge.
The results strongly supported the theory that proteins are true macromolecules.

Role of Noncovalent Bonds

Macromolecules such as polysaccharides, proteins, and nucleic acids are built from covalent bonds.
Noncovalent bonds specify the precise shape of a macromolecule.
Noncovalent bonds allow a macromolecule to bind other selected molecules.

Macromolecular Complexes

Covalent bonds allow small organic molecules to join together to form macromolecules, which can assemble into large macromolecular complexes via noncovalent bonds.

Ribosomes and ER

Electron micrograph of ribosomes.
Some ribosomes are free in the cytosol.
Others are attached to the membranes of the endoplasmic reticulum (ER).

Noncovalent Interactions within Macromolecules

Amino acids within a polypeptide chain can be hydrogen-bonded to each other.

Noncovalent Interactions between Macromolecules

Weak noncovalent bonds have less than 1/20th the strength of a strong covalent bond.
They are strong enough to provide binding only when many of them are formed simultaneously.

Macromolecule Shape

Noncovalent bonds specify the precise shape of a macromolecule.
Most proteins and many RNA molecules fold into a three-dimensional shape or conformation.
The shape/conformation is directed mostly by a multitude of weak, noncovalent, intramolecular bonds.
Disruptions affect conformation and biological activity.

Protein Binding

A large molecule (e.g., a protein) can bind to another protein through noncovalent interactions on the surface of each molecule.
In the aqueous environment, many individual weak interactions cause two proteins to recognize each other specifically and form a tight complex.
Electrostatic attractions occur between complementary positive and negative charges.

Macromolecule Selectivity

A macromolecule A randomly encounters other macromolecules (B, C, and D).
The surfaces of A and B, and A and C, are a poor match and form few weak bonds; thermal motion rapidly breaks them apart.
The surfaces of A and D match well and form enough weak bonds to withstand thermal jolting, so they stay bound to each other.

Molecular Movement

Molecules in the cell are in constant motion due to thermal energy.
Molecules diffuse inside the cell but constantly collide with other molecules, resulting in a “random walk.”
The smaller the molecule, the more rapidly it can diffuse through the cell cytosol.
Proteins and other large macromolecules diffuse through the cytosol more slowly.
Noncovalent interactions between macromolecules are facilitated by their close proximity in the cell and by many random collisions.

Types of Noncovalent Interactions

Hydrogen bonds
Electrostatic interactions
Van der Waals interactions
Hydrophobic effect

Hydrogen Bonds

Hydrogen bonds between the polar molecule urea and $H_2O$ molecules.
Hydrogen bonds between the bases in DNA.
$H_2O$ molecules joined together in a hydrogen-bonded lattice.

Hydrogen Bonds in Water

Two adjacent $H_2O$ molecules can form a hydrogen bond because they are polarized.
A slight positive charge is associated with the hydrogen atom, which is electrically attracted to the slight negative charge of the oxygen atom.
Oxygen is more electronegative than hydrogen (electrons shared unequally in this covalent bond), so the $H_2O$ molecule has electronegative and electropositive regions.

Hydrogen Bond Formation

In cells, hydrogen bonds commonly form between molecules containing oxygen or nitrogen.
The atom bearing hydrogen is considered the H-bond donor.
The atom that interacts with hydrogen is the H-bond acceptor.
Often, hydrogen is sandwiched between two electronegative atoms (O or N).
Hydrogen bonds have ~1/20 the strength of a covalent bond.

Electrostatic Interactions

An enzyme that binds a positively charged substrate will often have a negatively charged amino acid side chain at the binding site.
If they are in close enough proximity, partially charged groups on polar molecules have electrostatic interactions.

Van der Waals interactions

Dipole–dipole interactions: Partial positive side of a molecule (such as $H_2O$ and alcohol) attracts the partial negative side of another molecule.
Induced dipole–induced dipole interactions: Attraction between transient induced dipoles.
Dipole–induced dipole interactions: A permanent dipole in one molecule (e.g., $H_2O$ ) can induce a transient dipole in another molecule through momentary distortion of electron clouds.

Hydrophobic Effect

Nonpolar hydrocarbons do not form hydrogen bonds and are generally insoluble in $H_2O$ .
Hydrophobic molecules contain many nonpolar bonds and are usually insoluble in $H_2O$ .
Hydrocarbons, which contain many C-H bonds, are especially hydrophobic.

Hydrophobic Interactions

Hydrophobic interactions are spontaneous processes and result in an increase in the entropy of the Universe (\Delta S > 0).

Clustering of Hydrophobic Molecules

Hydrophobic molecules such as benzene tend to cluster together in aqueous solutions (hydrophobic effect).
The hydrophobic effect is powered by the increase in the entropy of water that results when hydrophobic molecules come together.
It is a powerful organizing force in biological systems, especially in membranes.

Entropy and Hydrophobic Interactions

Nonpolar solute molecules are driven together in water not primarily because they have a high affinity for each other but because, when they do associate, they release ordered water molecules around nonpolar molecules (e.g., benzene) into bulk water, which increases the entropy of the system.
This results in higher entropy.