Introduction: Common Macromolecules- Nucleic Acids.

A nucleic acid is a polymer made up of many nucleotides. A nucleotide is generally made of;

Typical Nucleotide.

i. Nitrogen-containing base; a heterocyclic molecule, containing a closed ring of atoms of which at least one is not a carbon atom and replaced with a nitrogen atom.

ii. Pentose sugar; meaning contains five carbon atoms in the sugar molecule.

iii. Phosphate Group; usually a phosphorus atom surrounded by a double bonded oxygen atom, single bonded to two oxygen negative ions and an oxygen atom.

Since the least complicated molecule is the phosphate group, it can easily be distinguished. However, for now, the distinguishing features for the nitrogen containing base will be the nitrogen atom. If the phosphate group is absent, the sugar-base combination is called a nucleoside.

The most common two forms of nucleotides are Ribonucleotides which form the nucleic acid Ribonucleic acid (RNA) and Deoxyribonucleotides which form the polynucleotide or nucleic acid Deoxyribonucleic acid (DNA), the molecules responsible for coding the proteins in the cell. In ribonucleotides, the sugar is ribose. In deoxyribonucleotides, the sugar is deoxyribose.

DNA V/S RNA.

The difference between the two is that the pentose sugar in DNA has one oxygen atom less in the hydroxyl group of Carbon atom 2. Also, since these two are the prime nucleic acids we shall be focusing on, their polymer structure is generally helical.

Another popular nucleotide is Adenosine Triphosphate (ATP) which is used as an energy currency in the cell. This will be clearer in later chapters.

ATP

Thus, nucleic acids are biopolymers composed of monomers called nucleotides. The term polynucleotide is a more accurate description of a single molecule of nucleic acid.

The nitrogenous bases of nucleotides belong to two families known as purines and pyrimidines.

In nucleotides, the base is joined to C-1 of the sugar and the phosphate group is attached to one of the other sugar carbons, usually C-5.

There are three phosphoryl groups; alpha(α), beta(β), and gama(γ) esterified to the C-5 hydroxyl group of the ribose. The linkage between ribose and the α-phosphoryl group is a phosphoester linkage because it includes a carbon and a phosphorus atom, whereas, the β- and γ-phosphoryl groups in ATP are connected by phosphoanhydride linkages that don’t involve carbon atoms. All Phosphoanhydride have considerable chemical potential energy, and ATP is no exception. This potential energy can be used directly in biochemical reactions.

The Phosphate Business

In polynucleotides, the phosphate group of one nucleotide is covalently linked to the C-5 oxygen atom of the sugar of another nucleotide creating a second phosphoester linkage. The entire linkage between carbons of adjacent nucleotides is called a phosphodiester linkage, because it contains two phosphoester linkages.

Nucleic acids contain many nucleotide residues and are characterized by a backbone consisting of alternating sugars and phosphates. In DNA, the bases of two different polynucleotide strands interact to form a helical structure.

DNA Back bone.

RNA contains ribose rather than deoxyribose, and is usually a single stranded polynucleotide. There are four kinds of RNA molecules: Messenger RNA (mRNA), transfer RNA (tRNA), Ribosomal RNA (rRNA), and a heterogeneous class of small RNAs that carry out a variety of different functions.

Introduction: Common Macromolecules- Polysaccharides.

Carbohydrates; As the name indicates, they consist of a Carbon atom (Carbo-) attached to a Hydrogen and an Oxygen atom in the ratio of 2:1, similar to water H₂O (-hydrate from hydra in latin meaning water). They have a general chemical formula of (CH₂O)_n where n is usually any number ranging from 2 onwards.

The most popular carbohydrates have n= 3 (triose) or 5 (pentose) or 6(hexose). Since most carbohydrates are sweet and sugary, sugar nomenclature end with “ose.”

They can be classified as single unit sugars which are calledmonosaccharides (mono means one, saccharide means sugar), ordisaccharide (“di” means two therefore two unit sugars joined together), or oligosaccharides (3 to 50 unit sugars joined together) or polysaccharides (“poly” means many and it is above 50 units of sugar joined together). The bond that holds the saccharides together to form carbohydrates is called glycosidic bond and is formed by the loss of a water molecule when two carbohydrates come together and are subsequently joined by the oxygen atom of one of the two saccharides molecules.

Glycosidic bond being formed by the proximity of two monosaccharides.

 

Carbohydrates are usually used as a food source since sugars are used to convert into energy . Example: Glucose (C₆H₁₂O₆) is a monosaccharide or single unit sugar and is a common source of energy for the body. However, glucose is generally stored as an aggregated giant molecule starch in plants or glycogen in animals. They are polysaccharides or polymers (macromolecules). Actually “poly” means many, and “mer” means molecules therefore it means many molecules.

Three important disaccharides are maltose, lactose, and sucrose which are used as fodder to either make the storage macromolecules or to break-down into monosaccharides for converting the sugar into energy.

In addition to it’s role as energy storage, carbohydrates are also used in plant cell wall in the form of the polysaccharide cellulose to give the cell structure, and is an important signal receptor on the plasma membrane of cells where the signal will induce the cell to perform specific functions. This is done when oligosaccharides linked to proteins on the plasma membrane work as signal receptors or markers for cell recognition and interaction.

All monosaccharides contain hydroxyl groups (OH) and are therefore alcohols. Sugar structures can be represented in many ways. Example: Ribose (the most common 5-carbon sugar can be shown as a linear molecule containing 4 hydroxyl groups and one aldehyde group.

Ribose- Fischer Projection.

This linear representation is called a Fischer projection. In its usual bio chemical form, however, the structural ribose is a ring with a covalent bond between the carbon of the aldehyde group (C-1) and the oxygen of the (C-4) hydroxyl group. This ring form is known as Haworth projection. The ring is not actually flat, it can adopt about twenty different conformations in which certain ring atoms are out-of-plane.

Ribose- Haworth’s Projection. Click on image for credit.

Another example is Glucose, which is the most abundant 6-Carbon sugar. (Insert Diagram) It is the monomer of the polysaccharide Cellulose and the storage polysacchride Glycogen and Starch.

Formation of Glycogen from Glucose. Click on image for credit.

In these polysacchrides, each glucose residue is joined covalently to the next bio covalent bond between C-1 of one glucose molecule and a hydroxyl group of another. This bond is called the glycosidic bond. In cellulose, C-1 of each glucose residue is joined to the C-4 hydroxyl group of the next residue. The hydroxyl groups on adjacent chains of cellulose interact non-covalently, creating strong insoluble fibers.

 

Introduction: Mass Units and Common Macromolecules- Proteins.

When we discuss molecules and bio polymers we will often refer to their molecular weight or relative molecular mass (Mr) this is the mass of a molecule relative to 1/12 the mass of an atom of carbon isotope -12 (which is exactly 12 atomic mass units. Don’t think too much into it, simply count the atom in the periodic table according to the number of protons it contains).

Now because Mr is a relative quantity, it is dimensionless and has no units associated with its value. The absolute molecular mass of a compound has the same magnitude as the molecular weight, except that it is expressed in units called Daltons; 1 Dalton = 1 atomic mass unit.

The molecular mass is also called the molar mass because it represents the mass, measured in grams, of one mole, which is Avogadro’s constant number = 6.023 × 10²³. So 1 mole of an atom or molecule contains 6.023 × 10²³ atoms or molecules and that in turn will give us how much the molecule will weigh in grams.

The molecular mass of a typical protein is 38,000 daltons..

The common macromolecules that we shall deal with in the coming chapters are proteins, polysaccharides, nucleic acids and lipids. We shall deal with one in each post:

a-            Proteins.

They are structurally important to the cell since they are the basic components of which the cytoskeleton is made, and functionally important since it is responsible for catalyzing reactions in the form of enzymes, have mobility functions, act as signal molecules for the cell and are part of a complex to form receptors for those signals and pretty much most other complicated functions. Due to these reasons, they are structurally complex as well.

Proteins are large polymers of amino acids joined together throughpeptide bonds to form polypeptides or in other words proteins. This is unclear unless you know what each bolded syllable is.

Amino Acid. Click on link for image credit

First, Amino Acids. Each amino acid consists of a central carbon atom bonded to a;

i-             Carboxylic-acid group (COOH); A carbon atom double-bonded to an oxygen atom and single bonded to a hydroxyl group (O-H).

ii-            Amino group (NH₂); This is simply a nitrogen atom single bonded to two hydrogen atoms.

iii-           Hydrogen atom;

iv-           A distinctive side-chain that is unique to each type of amino acid, usually referred to as the “R” group. Thus, amino acids differ only in their side chains.

Amino acids get their name because of the amino group and the carboxylic acid group.

When two amino acids come close together, the hydroxyl group (OH) of the carboxylic-acid, which is polar, attracts a hydrogen atom of the amino group of the other amino acid and in the process, forms and releases a water molecule (See below image). This leads to the formation of a peptide bond which is a covalent bond between the carbon of the carboxylic-acid group of the first amino acid and the nitrogen of the amino group of the second amino acid. When many amino acids are linked together through peptide bonds, they form a polypeptide chain (or proteins).

Formation of a Peptide Bond. Click on image for credit.

Proteins are structurally complex. If you look at one (below), you can only see chaos. This is due to the fact that when amino acids begin to form peptide bonds with one another, they do not line up into a straight linear structure, rather, they begin to spiral and coil due to the interaction of their side chains with one another forming various types of (mostly) hydrogen and (sometimes) sulphur bonds.

The three dimensional shape of a protein is determine largely by the sequence of amino acid residues. This sequence of information is encoded in the gene of the protein and it is important because the protein’s 3-D structure or conformation is what does their jobs.

Many enzymes for instance contain a cleft (groove) called the active site whose function is to catalyze reactions that depend on this structure.

Enzyme with active site (cleft) shown. Click on image for credit.

Substrate is the molecule(s) that require catalysis and when bind with the active site of the enzyme, undergo specific reactions (more on it later).

Introduction- Organic Compounds, Functional Groups and Linkages.

Much of biochemistry deals with biopolymers that are macromolecules created by joining many smaller organic molecules (monomers) via condensation (removal of element of water). Each monomer that makes a macromolecular chain is called a residue.

In some cases like carbohydrates (more on it later), a single monomer or residue is repeated many times, in other cases like proteins and nucleic acids, a variety of residues are connected in a specific order.

The residues are added and converted into a polymer by repeating the same enzyme catalyzed reaction. Thus all of the residues in a biopolymer are aligned in the same direction.

Biopolymers have properties that are very different from those of their constituent monomers. Example: Starch is not soluble in water and does not taste sweet although it is a polymer of the sugar Glucose, which has both those properties.  So we can conclude that each new level of organization results in properties that cannot be predicted just from those of the previous level.

The levels of complexity in increasing order are atoms, then molecules, then biopolymers, then organelles then cells, tissue, organ, and all organisms and systems.

 

The types of organic compounds, functional groups and linkages commonly seen in biochemistry are;

Organic Compounds, Functional Groups and Linkages.

PS: Under most biological conditions, carboxylic acids exist as carboxylate anions: COO^– and amines exist as ammonium ions: NH₃⁺ .

Please make sure you memorize the names and structures of the functional groups.

Biochemical reactions involve specific chemical bonds or parts of molecules called functional groups which we will deal with several times.

• Ester and Ether are common linkages found in fatty acids and lipids.
• Amide linkages are found in proteins.
• Phosphate ester and Phosphoanhydride linkages occur in nucleotides.

Introduction.

Biochemistry is the discipline that uses the principles and language of chemistry to explain biology at the molecular level.

In general the same chemical compounds and the same central metabolic processes are found in organisms as distantly related as bacteria and humans. In other words the basic principles of biochemistry are common to all living organisms.

We will find that much of our study is devoted to considering how enzymes and nucleic acids are central to the chemistry of life. In order to understand how nucleic acids store and transmit genetic information, we must understand their structure and their role in encoding the enzyme proteins which catalyze (speed up) the synthesis and degradation of bio molecules, including nucleic acids themselves.

Only six non-metallic elements – oxygen, carbon, hydrogen, nitrogen, phosphorus, and sulfur account for more than 97% of the weight of most organisms. All these elements can form stable covalent bonds.

Water is a major component of cells and accounts for the high percentage of oxygen atoms. And some elements such as silicon, aluminum and iron are present only in trace amounts in cells.

Altogether, a total of 29 different elements are commonly found in living organisms. These include 5 ions that are essential in all species: calcium (Ca²⁺),  potassium (K⁺), sodium (Na⁺), Magnesium (Mg²⁺) and chloride (Cl^–).

The 29 Elements of Life encircled.

Important to biochemistry’s evolution was when in 1828 Friedrich Wohler synthesized the organic compound Urea by heating the inorganic compound ammonium cyanate. This experiment showed for the first time that compound found exclusively in living organisms could be synthesized from common inorganic substances. We now understand that the synthesis and degradation of biological substances obey the same chemical and physical laws as those outside biology. So no special processes are required to explain life at the molecular level.

Most of the solid material of cells consists of carbon containing compounds. The study of such compounds falls into the area of organic chemistry. There is many similarities between the discipline of organic chemistry and biochemistry, but organic chemists are more interested in reaction that take place in the lab (in vitro) where as biochemists would like to understand how reactions happen in living cells (in vivo).