Biochemicals

Major classes of biochemicals are carbohydrates, lipids, proteins and amino acids, nucleic acids, and enzymes.

Carbohydrates are the most abundant class of organic compounds found in living organisms. They originate as products of photosynthesis, an endothermic reductive condensation of carbon dioxide requiring light energy and the pigment chlorophyll.

n CO2 + n H2O + energy CnH2nOn + n O2

As noted here, the formulas of many carbohydrates can be written as carbon hydrates, Cn(H2O)n, hence their name. The carbohydrates are a major source of metabolic energy, both for plants and for animals that depend on plants for food. Aside from the sugars and starches that meet this vital nutritional role, carbohydrates also serve as a structural material (cellulose), a component of the energy transport compound ATP, recognition sites on cell surfaces, and one of three essential components of DNA and RNA. Carbohydrates are called saccharides or, if they are relatively small, sugars.

Lipids are fatty acid esters, a class of relatively water-insoluble organic molecules, which are the "basic" components of biological membranes. The lipids are a large and diverse group of naturally occuring organic compounds that are related by their solubility in nonpolar organic solvents (e.g. ether, chloroform, acetone & benzene) and general insolubility in water. There are three forms of lipids: phospholipids, steroids. and triglycerides.

Lipids consist of a polar or hydrophilic (attracted to water) head and one to three nonpolar or hydrophobic (repelled by water) tails. Since lipids have both functions, they are called amphiphilic. The hydrophobic tail consists of one or two (in triglycerides, three) fatty acids. These are unbranched chains of carbon atoms (with the correct number of H atoms), which are connected by single bonds alone (saturated fatty acids) or by both single and double bonds (unsaturated fatty acids). The chains are usually 14-24 carbon groups long.

For lipids present in biological membranes, the hydrophilic head is from one of three groups:

Glycolipids, whose heads contain an oligosaccharide with 1-15 saccharide (sugar) residues.
Phospholipids, whose heads contain a positively charged group that is linked to the tail by a negatively charged phosphate group. Sterols, whose heads contain a planar steroid ring, for example, cholesterol (only in animals). In an aqueous environment, the heads of lipids are turned towards the environment, and the tails are turned towards a hydrophobic region of another molecule. With lots of lipids present, the tails "prefer" to turn toward each other, forming a hydrophobic region. This can be a bilayer or a micelle. Micelles are spheres and can only reach a certain size, whereas bilayers have no limit to their extension. They can also form tubules.

Proteins are a primary constituent of living things and one of the chief classes of molecules studied in biochemistry. Proteins provide most of the molecular machinery of cells. Many are enzymes or subunits of enzymes. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the "cytoskeleton." Each protein molecule is an unbranched chain or "polymer" of amino acids.

A primary component of all living things, proteins are also nutrient sources for organisms that do not produce their own energy from sunlight. Proteins differ from carbohydrates chiefly in that they contain much nitrogen and a little bit of sulfur, besides carbon, oxygen and hydrogen.

Proteins, from the Greek proteios, meaning first, are a class of organic compounds which are present in and vital to every living cell. In the form of skin, hair, callus, cartilage, muscles, tendons and ligaments, proteins hold together, protect, and provide structure to the body of a multicelled organism. In the form of enzymes, hormones, antibodies, and globulins, they catalyze, regulate, and protect the body chemistry. In the form of hemoglobin, myoglobin and various lipoproteins, they effect the transport of oxygen and other substances within an organism.

Proteins are generally regarded as beneficial, and are a necessary part of the diet of all animals. Humans can become seriously ill if they do not eat enough suitable protein, the disease kwashiorkor being an extreme form of protein deficiency. Protein based antibiotics and vaccines help to fight disease, and we warm and protect our bodies with clothing and shoes that are often protein in nature (e.g. wool, silk and leather).

The deadly properties of protein toxins and venoms is less widely appreciated. Botulinum toxin A, from Clostridium botulinum, is regarded as the most powerful poison known. Based on toxicology studies, a teaspoon of this toxin would be sufficient to kill a fifth of the world's population. The toxins produced by tetanus and diphtheria microorganisms are nearly as poisonous. A list of highly toxic proteins or peptides would also include the venoms of many snakes, and ricin, the toxic protein found in castor beans.

Despite the variety of their physiological function and differences in physical properties--silk is a flexible fiber, horn a tough rigid solid, and the enzyme pepsin water soluble crystals--proteins are sufficiently similar in molecular structure to warrant treating them as a single chemical family. When compared with carbohydrates and lipids, the proteins are obviously different in fundamental composition. The lipids are largely hydrocarbon in nature, generally being 75 to 85% carbon. Carbohydrates are roughly 50% oxygen, and like the lipids, usually have less than 5% nitrogen (often none at all). Proteins and peptides, on the other hand, are composed of 15 to 25% nitrogen and about an equal amount of oxygen. The distinction between proteins and peptides is their size. Peptides are in a sense small proteins, having molecular weights less than 10,000.

In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. In biochemistry, this shorter and more general term is frequently used to refer to alpha amino acids: those amino acids in which the amino and carboxylate functionalities are attached to the same carbon.

Amino acids are a biochemical building block. They form long chemical chains called proteins (see below), and shorter chains called peptides.

Twenty amino acids are encoded by the standard genetic code and are called proteinogenic. Proline is the only cyclic proteinogenic amino acid. Other amino acids contained in proteins are usually formed by modification after translation (protein synthesis). These modifications are often essential for the function of the protein. At least two amino acids other than the standard 20 are sometimes incorporated into proteins during translation:

Selenocysteine is incorporated into some proteins at a UGA codon, which is normally a stop codon.

Pyrrolysine is used by some methanogens in enzymes that they use to produce methane. It is coded for similarly to selenocysteine but with the codon UAG instead.
Over 500 amino acids have been found in nature. Some of them have also been found in meteoritic material. Microorganisms and plants often produce very uncommon amino acids, which can be found in peptidic antibiotics (for example nisin or alamethicin). Lanthionine is a sulfide bridged alanine dimer which is found together with unsaturated amino acids in lantibiotics (antibiotic peptides from microbial origin). 1-Aminocycloproane-1-carboxylic acid ACC is a small disubstituted cyclic amino acid and a key intermediate in the production of the herbal hormone ethylene.

In addition to amino acids for protein synthesis, there are other biologically important amino acids, such as the neurotransmitter GABA, carnitine (used in lipid transport within a cell), ornithine, citrulline, homocysteine, hydroxyproline, hydroxylysine, and sarcosine.

Some of the 20 amino acids in the genetic code are called essential amino acids, because they cannot be synthesized by the body from other compounds through chemical reactions, but instead must be taken in with food. In humans, the essential amino acids are lysine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan, valine, and (in children) histidine and arginine.

Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of family of biopolymers. The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2'-deoxyriboses). Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine are possible in both RNA and DNA, while thymine is possible only in DNA and uracil is possible only in RNA.

The sugars and phosphates in nucleic acids are connected to each other in an alternating chain through shared oxygens (forming a phosphodiester functional group). Using the conventional nomenclature, the carbons to which the phosphate groups are attached are the 3' and the 5' carbons. The bases extend from a glycosidic linkage to the 1' carbon of the pentose ring.

Nucleic acids may be single-stranded or double-stranded. A double-stranded nucleic acid consists of two single-stranded nucleic acids hydrogen-bonded together. RNA is usually single-stranded, but any given strand is likely to fold back upon itself to form double-helical regions. DNA is usually double-stranded, though some viruses have single-stranded DNA as their genome.

Nucleic acids are primarily biology's means of storing and transmitting genetic information, though RNA is also capable of acting as an enzyme.

The polymeric structure of DNA may be described in terms of monomeric units of increasing complexity. In the top shaded box of the following illustration, the three relatively simple components mentioned earlier are shown. Below that on the left , formulas for phosphoric acid and a nucleoside are drawn. Condensation polymerization of these leads to the DNA formulation outlined above. Finally, a 5'- monophosphate ester, called a nucleotide may be drawn as a single monomer unit, shown in the shaded box to the right. Since a monophosphate ester of this kind is a strong acid (pKa of 1.0), it will be fully ionized at the usual physiological pH (ca.7.4). Names for these DNA components are given in the table to the right of the diagram. Isomeric 3'-monophospate nucleotides are also known, and both isomers are found in cells. They may be obtained by selective hydrolysis of DNA through the action of nuclease enzymes. Anhydride-like di- and tri-phosphate nucleotides have been identified as important energy carriers in biochemical reactions, the most common being ATP (adenosine 5'-triphosphate).

A complete structural representation of a segment of the DNA polymer formed from 5'-nucleotides may be viewed by clicking on the above diagram. Several important characteristics of this formula should be noted.

• First, the remaining P-OH function is quite acidic and is completely ionized in biological systems.
• Second, the polymer chain is structurally directed. One end (5') is different from the other (3').
• Third, although this appears to be a relatively simple polymer, the possible permutations of the four nucleosides in the chain become very large as the chain lengthens.
• Fourth, the DNA polymer is much larger than originally believed. Molecular weights for the DNA from multicellular organisms are commonly 109 or greater.

Information is stored or encoded in the DNA polymer by the pattern in which the four nucleotides are arranged. To access this information the pattern must be "read" in a linear fashion, just as a bar code is read at a supermarket checkout. Because living organisms are extremely complex, a correspondingly large amount of information related to this complexity must be stored in the DNA. Consequently, the DNA itself must be very large, as noted above. Even the single DNA molecule from an E. coli bacterium is found to have roughly a million nucleotide units in a polymer strand, and would reach a millimeter in length if stretched out. The nuclei of multicellular organisms incorporate chromosomes, which are composed of DNA combined with nuclear proteins called histones. The fruit fly has 8 chromosomes, humans have 46 and dogs 78 (note that the amount of DNA in a cell's nucleus does not correlate with the number of chromosomes). The DNA from the smallest human chromosome is over ten times larger than E. coli DNA, and it has been estimated that the total DNA in a human cell would extend to 2 meters in length if unraveled. Since the nucleus is only about 5mm in diameter, the chromosomal DNA must be packed tightly to fit in that small volume. In addition to its role as a stable informational library, chromosomal DNA must be structured or organized in such a way that the chemical machinery of the cell will have easy access to that information, in order to make important molecules such as polypeptides. Furthermore, accurate copies of the DNA code must be created as cells divide, with the replicated DNA molecules passed on to subsequent cell generations, as well as to progeny of the organism. The nature of this DNA organization, or secondary structure, will be discussed in a later section.

The high molecular weight nucleic acid, DNA, is found chiefly in the nuclei of complex cells, known as eucaryotic cells, or in the nucleoid regions of procaryotic cells, such as bacteria. It is often associated with proteins that help to pack it in a usable fashion. In contrast, a lower molecular weight, but much more abundant nucleic acid, RNA, is distributed throughout the cell, most commonly in small numerous organelles called ribosomes. Three kinds of RNA are identified, the largest subgroup (85 to 90%) being ribosomal RNA, rRNA, the major component of ribosomes, together with proteins. The size of rRNA molecules varies, but is generally less than a thousandth the size of DNA. The other forms of RNA are messenger RNA , mRNA, and transfer RNA , tRNA. Both have a more transient existence and are smaller than rRNA. All these RNA's have similar constitutions, and differ from DNA in two important respects. As shown in the following diagram, the sugar component of RNA is ribose, and the pyrimidine base uracil replaces the thymine base of DNA. The RNA's play a vital role in the transfer of information (transcription) from the DNA library to the protein factories called ribosomes, and in the interpretation of that information (translation) for the synthesis of specific polypeptides. These functions will be described later.

An enzyme is a protein, or assemblage of protein molecules, that catalyze chemical reactions in living organisms. Within biological cells many chemical reactions occur, but without enzymes, they would happen too slowly to sustain life. An RNA enzyme or "ribozyme" is made of RNA instead of protein. Generally ribozymes only catalyze RNA splicing.

Enzymes can also serve to couple two or more reactions together, so that a thermodynamically favourable reaction can be used to "drive" a thermodynamically unfavorable one. One of the most common examples is enzymes which use the dephosphorylation of ATP to drive some otherwise unrelated chemical reaction.

Chemical reactions need a certain amount of activation energy to take place. Enzymes can increase the reaction speed by favoring or enabling a different reaction path with a lower activation energy, making it easier for the reaction to occur. Enzymes are large proteins that catalyze (accelerate) chemical reactions. They are essential for the function of cells. Enzymes are usually specific as to the reactions they catalyze and the chemicals (substrates) that are involved in the reactions. Complementary structural properties of the enzyme and substrate are responsible for this specificity. Many enzymes are composed of several proteins that act together as a unit. Most parts of an enzyme have regulatory or structural purposes. The catalyzed reaction takes place in only a small part of the enzyme called the active site.
Enzymes are essential to living organisms, and a malfunction of even a single enzyme out of approximately 2,000 present in our bodies can lead to severe or lethal illness. An example of a disease caused by an enzyme malfunction in humans is phenylketonuria (PKU). The enzyme phenylalanine hydroxylase, which usually converts the essential amino acid phenylalanine into tyrosine does not work, resulting in a buildup of phenylalanine that leads to mental retardation. Enzymes in the human body can also be influenced by inhibitors in good or bad ways. Aspirin, for example, inhibits an enzyme that produces prostaglandins (inflammation messengers), thus suppressing pain. But not all enzymes are in living things. Enzymes are also used in everyday products such as washing detergents, where they speed up chemical reactions involved in cleaning the clothes (for example, breaking down blood stains).

Nutrition in animals relies on digestive enzymes such as salivary amylase, trypsin and chymotrypin. Their primary role is for the digestion of food and making nutrients available to all of the body processes which need them. Another class of enzymes is called metabolic enzymes. Their role is to catalyze chemical reactions involving every process in the body, including the absorption of oxygen. Most of our cells (an exception being erythrocytes), would literally starve for oxygen even with an abundance of oxygen without the action of the enzyme, cytochrome oxidase. Enzymes are also necessary for muscle contraction and relaxation. The fact is, without both of these classes of enzymes, (digestive and metabolic) life could not exist.