Protein, first... and when it goes awry

(Part 1 of 2)

Come to think about it, the human body from head to foot is mainly composed of proteins: e.g., keratin in hair, nails, and skin; hemoglobin, fibrinogen and thrombin in blood; actin and myosin in muscle; collagen in tendon, cartilage, skin and cornea; various enzymes; and numerous other proteins distributed throughout the body. In fact, the human body is about 45 percent protein. Protein is an essential substance needed for body-building, maintenance, protection, regulation or repair. Along with nucleic acids, carbohydrates and lipids, proteins are truly major “building blocks of life.”

Protein, ‘protos’

Proteins are large biological molecules consisting of one or more polypeptide chains, with up to thousands of amino acid units (residues). Polypeptides with molar mass below 10,000 daltons (i.e., with about 90 amino acid residues) are often called peptides while longer polypeptides are usually classified as proteins. This classification is somewhat arbitrary because sometimes the words “peptide” and “protein” are used interchangeably, especially for polypeptides with intermediate lengths. The amino acid residues in a peptide or protein are joined by so-called peptide bonds formed between adjacent amino acids. The amino acid sequence is the order in which amino acids are positioned in the linear chain of a polypeptide, from the N-terminus which contains free amino group to the C-terminus which contains free carboxyl group. Proteins are synthesized from 20 standard amino acids which are directly dictated by gene through the genetic code.

The word “protein” that was derived from a Greek word meaning “first” was coined by Jöns Jacob Berzelius in 1838, for “organic compound that is the chief component of fibrin and albumin” and is “the fundamental substance in animal nutrition.” Since then, many studies ushered the advancement of protein chemistry. Frederick Sanger painstakingly determined the complete amino acid sequence of insulin, at a time when amino acid sequencing was an extremely difficult task. The three-dimensional (3-D) structures of myoglobin and hemoglobin were determined by the teams of John Cowdery Kendrew and Max Ferdinand Perutz, respectively. For their contributions, Sanger was awarded the Nobel Prize in Chemistry in 1958, while Kendrew and Perutz shared the Nobel Prize in Chemistry in 1962. Robert Bruce Merrifield developed the solid phase method for chemical synthesis of peptides, for which he was recognized with the Nobel Prize in Chemistry in 1984.

Proteins carry out varied functions in the cells. Enzymes catalyze biochemical reactions and are involved in metabolic processes; an example is salivary amylase which is involved in the digestion of starch. Transport proteins bind and carry specific molecules or ions; for instance, hemoglobin transports oxygen from the lungs to various body tissues. Structural proteins, e.g., collagen, form the matrix materials that hold tissues together, and confer strength to biological components. Antibodies or immunoglobulins act in immune response and serve to neutralize foreign materials which can cause infection or toxicity. Hormones are responsible for the regulation of cellular processes; insulin, for example, regulates carbohydrate metabolism by causing cells to take up glucose from blood. Receptors (e.g., acetylcholine receptor) and ion channels (e.g., calcium channel) bind key molecules and ions, respectively, and detect signal which is translated into another type of signal. Signaling is the way by which cells communicate with one another, allowing vital processes like muscle contraction, to occur.

Proteins undergo structural organization at different levels. The primary structure is defined by amino acid sequence in a polypeptide chain. The secondary structure refers to the shape of the polypeptide which is predominantly alpha helix and beta sheet. A major aspect of the secondary structure is the stabilization brought about by hydrogen bonds that connect the corresponding hydrogen atoms and oxygen atoms in a polypeptide chain. The tertiary structure is defined by the 3-D shape of the polypeptide resulting from various interactions between amino acid residues, causing the peptide to fold. The structure defined by interactions between two or more polypeptide chains, or subunits, that make up a protein complex is the quaternary structure.

Insulin is an example of a protein with two subunits. It is ambiguously referred to as a peptide because of the small number of amino acid residues, or a protein because of the presence of two subunits making it sort of a protein complex. Bovine insulin which was originally sequenced by Sanger consists of A and B chains, with 21 and 30 amino acid residues, respectively, joined by disulfide bonds formed between cysteine residues. It differs from human insulin only in three amino acid residues, and so it is available to human with insulin deficiency, for the same function as human insulin in the control of blood glucose level.

Hemoglobin is a protein with four subunits, two identical alpha chains and two identical beta chains, each consisting of about 140 amino acid residues. Each subunit binds an oxygen molecule through the iron atom found in the heme group, making it possible for a single hemoglobin molecule to bind four oxygen molecules. The oxygenated hemoglobin gives blood (particularly the red blood cells) its red color. Myoglobin, protein that binds and stores oxygen in muscle, has only one polypeptide chain with 3-D structure very similar to that of a single chain of hemoglobin.

(To be concluded)

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Dr. Elsie C. Jimenez, a member of the Philippine-American Academy of Science and Engineering, is a retired professor of chemistry at the University of the Philippines Baguio. She undertook research on peptides from cone snails, for which she is co-inventor in several US patents on these peptides. She is currently doing research on proteins and toxins of red tide organisms at the Marine Science Institute, UP Diliman. E-mail her at [email protected].