The term ‘protein’ is derived from the Greek word proteious, meaning ‘of the first rank’. Proteins are indeed ‘of the first rank’ of importance in all living creatures. Proteins consist of chains of amino acids joined end to end by peptide bonds and are involved in all manner of biological processes and reactions. The majority of the chemical reactions in the body are controlled by enzymes, all of which are proteins. The carriage of oxygen in the blood from the lungs to the periphery is possible because a protein, haemoglobin, forms a complex with oxygen, while in muscle another protein, myoglobin, acts as an oxygen transporter. Muscle contraction is dependent on two proteins, actin and myosin. Linear protein molecules, in the form of collagen, give tensile strength to tissues. Antibodies, produced as part of our body defence mechanisms, are proteins, as are the membrane receptors that respond to hormones and neurotransmitters. Some hormones, for example insulin, are also proteins. Membrane ion channels, as those activated during a nerve impulse, are proteins. A multitude of proteins are involved in growth and development. Thus it is obvious that proteins play a crucial role in living processes.
In spite of the variety and complexity of proteins they are composed of only twenty different amino acids. Nine of these are essential amino acids, that is they cannot be synthesized within the body but are derived from dietary sources. The amino acids in each protein occur in a unique sequence, from 100 to more than 1000, in accordance with the widely ranging size of protein molecules.
The amino acid sequence in a particular protein is determined by its gene. It is proteins and only proteins that are described by the genetic code. The most overarching, important rule in biology is that DNA (i.e. genes) makes RNA (messenger) that in turn makes protein. Thus it is essential that genes are accurately transcribed and that the messengers are accurately translated if the amino acid sequences in proteins are to be accurate. If the gene sequence is faulty because of an inherited mutation, then neither transcription or translation can correct the problem, and a faulty protein or no protein will be the result. Thus genetic disease that results when faulty genetic sequences are passed from parents to their offspring is a consequence of the loss of function due to faulty proteins.
Two conditions serve as examples. Human haemoglobin consists of four amino acid chains, combined with haem groups, namely two alpha and two beta chains. If glutamate is exchanged for valine in position 6 on the two beta chains, the resulting haemoglobin is faulty and sickle cell disease is the result. In the haemoglobin molecule there are 574 amino acids, and the replacement of just two glutamates by two valines leads to loss of normal function. In cystic fibrosis one tiny piece of the gene has been lost, resulting in the loss of a single amino acid, phenylalanine, from a protein containing 1480 amino acids; this small change produces a lethal genetic disease.
Although the sequences of amino acids in proteins are linear, the protein structures formed are rarely so, the chains being folded and linked together to give more globular structures. It is the amino acid sequence that determines the folding pattern, common motifs being the ‘alpha helix’ and the ‘pleated beta sheet’. Disulphide bridges often form between sulphur-containing amino acids which become adjacent by folding, although they may be very distant in the linear sequence. Other sites on the folded molecules may become phosphorylated (phosphate groups added) or glycosylated (linked to sugar molecules), or may bind with non-protein groupings (e.g. haem in haemoglobin).
Digestion of proteins in the diet gives rise to amino acids that are absorbed into the bloodstream from the gastrointestinal tract. These amino acids can be used either as an energy source or in the synthesis of new proteins. In this way an individual amino acid may be part of many different protein molecules in many different species, including man, at different times.
The tertiary structure (the way the linear chain is folded) of many proteins is now known and this in turn has led to an understanding of their functions. Active centres and binding pockets have been revealed, into which substrates can fit — for example to bind a molecule which is to be cleaved, as in digestion, or to bind a molecule of neurotransmitter. The consequence for the protein is often a conformational change, which leads to the cleavage of the substrate, as in digestion, or the opening of an ion channel, as with some neurotransmitters. Loss by diffusion of the cleaved substrate or of the transmitter then allows the conformational change to reverse.
— Alan W. Cuthbert
See also amino acids; enzymes; genetics, human; membrane receptors.
The Oxford Companion to the Body. Copyright © 2001, 2003 by Oxford University Press. All rights reserved.
