Proteins
4.1 Protein function
When we ask students what they think of when they hear the wordprotein, we are usually greeted with the same response. Typically, they respond with the classic textbook answer that proteins ‘are needed for growth and repair’ of tissues and that we can obtain them by eating protein-rich food such as chicken, fish, eggs and milk, etc. How- ever, from this point forth, we would like you to extend your understanding of proteins beyond growth and repair and begin to appreciate that pro- teins are the macromolecules that are essential to life. In short, they could be referred as the cellu- lar action molecules. Houston (2006) captures this point entirely by stating:‘Everything we do, every- thing we are and everything we become depend on the action of thousands of different proteins.’
There are hundreds of thousands of proteins present in the human body and each is likely to perform a unique role within our cells. The average adult contains approximately 10–12 kg of protein, of which 60–75% is located within our muscles. The term proteome refers to all of the proteins present within the cell, and many sci- entists are devoted to characterizing the function of all proteins present in the proteome. To use a simple analogy, you could begin your study of proteins by thinking of them in the same way that you view friends and family in your own lives.
For example, similar to how friends and family members play a particular role in you life, each of our cellular proteins also play important roles, without which our cells would not operate as efficiently and may become susceptible to disease.
For example, the skeletal muscle cells of patients with McArdle’s syndrome lack the pro- tein (in this case an enzyme) known as glycogen phosphorylase, and due to this they cannot break down muscle glycogen stores to provide energy. As a result, these patients fatigue within seconds of intense physical exertion and report extreme pain and stiffness. Consequently, their overall quality of life is severely hindered (Salter, 1967). This example alone clearly illustrates the importance of correctly functioning proteins. In the next section, we look more closely at some
of the diverse roles that proteins can play in our bodies, many of which you will already be familiar with from Chapters 1–3.
4.1.1 General protein function
Proteins can perform an array of cellular functions, such as participating in biochemical reactions, trans- porting substances into and out of cells, maintaining cell structure, producing movement and transmitting important information. For this reason, proteins are often classified into a number of categories based on their cellular function, as shown in Figure 4.1. It is important to note, however, that not all proteins can be confined to a solitary function – many proteins perform diverse roles.
Catalytic
Many proteins function as enzymes (i.e. biolog- ical catalysts), which are defined as substances
that can accelerate biochemical reactions without being altered themselves. For example, we briefly outlined earlier how the enzyme glycogen phos- phorylase is involved in breaking down muscle glycogen stores to provide our muscles with ATP and, thus, the energy to exercise. An understanding of enzyme function and their regulation is there- fore crucial for the study of sport and exercise metabolism. For this reason, we dedicate a whole section to this topic later in this chapter.
Transport and storage
There are many substances that are transported into and out of cells, into and out of intracel- lular organelles and also from one site of the body to another. The transportation of these substances is possible through the action of proteins. For example, the oxygen we breathe can be transported to our muscles via the protein haemoglobin, the major protein found in the
FUNCTION
Signalling
Transport
Catalysis A
B Structure
Regulation off on
Movement
Figure 4.1 Schematic illustration of the diverse functions of proteins
blood. Similarly, the protein myoglobin, present in our muscles, can then receive this oxygen, store it and also transport it inside the muscle cell. Additionally, proteins can span across cell membranes and acts as channels or pumps, so as to regulate the flow of important molecules into and out of cells.
Hormones
Many proteins also function ashormones, defined as proteins secreted by cells of the endocrine system, which regulate activity of cells in other parts of the body. The importance of hormone action can be easily illustrated through the action of the hormoneinsulin, a hormone released from the pancreas following an increase in blood sugar (glucose) levels which occurs following the consumption of a meal, especially if it has a high carbohydrate content. Insulin regulates blood glucose concentration by binding to a receptor protein present in the plasma membrane of other cells (most notably skeletal muscle), which initiates an intracellular signalling cascade that ultimately causes the cell to increase its uptake of glucose, thereby returning the blood glucose concentration to baseline values.
Patients withdiabeteshave difficulty maintain- ing blood glucose levels within basal levels and, if left untreated, the resultinghyperglycaemia(i.e.
high blood glucose) can, in extreme cases, lead to a coma and cause death. Fortunately, daily injections of insulin can help overcome the defects in insulin secretion or action that is associated with type 1 and 2 diabetes, respectively. The hormonal control of exercise metabolism is discussed in Chapter 7 of this book.
Signalling
Many proteins are also involved in signalling roles involving communication between and within cells. In the above example, the insulin receptor in the cell membrane of the muscle cell is bound by insulin released from the pancreas (i.e. cell-to-cell communication) which then initiates an intracellular signalling cascade (i.e.
intracellular communication), leading to increased glucose uptake.
Although the precise proteins involved in the insulin signalling cascade remains an active area of research, it is thought to work via series of phosphorylation reactions where proteins known as kinasesphosphorylate a target protein, thereby rendering the latter active. This, in turn, may lead to phosphorylation of another protein (and so on) until the appropriate cellular response has been achieved. Similarly, when we perform repeated bouts of exercise (e.g. training) our muscle cells can respond to both extracellular and intracellular signals, which, in time, activate the relevant sig- nalling cascade to help our muscles become more efficient to deal with the metabolic stress induced by exercise.
A simplistic way to think of proteins as sig- nalling molecules is to imagine them in a game of dominoes. For example, when the signal has been initiated (i.e. the first domino has been toppled), it leads to repeated toppling of the domino chain until the necessary response has been achieved.
Contractile
As we saw in Chapter 2, the proteins actin and myosin (known as ‘myofibrillar’ proteins because they are located in the myofibrils of muscle cells) are sometimes referred to as the motor proteins, as they are responsible for muscle contraction. Essentially, these proteins turn the chemical energy stored within the bonds of ATP into mechanical work. They therefore form the molecular basis for muscle contraction.
Structural
As alluded to in Chapter 3 in reference to the cytoskeleton of cells, many proteins function to maintain cell structure. One important structural protein in skeletal muscle cells is dystrophin, the specific function of which is to anchor the contrac- tile apparatus (i.e. the myofibrils) to the plasma membrane. The importance of the dystrophin protein is evident by examining patients with Duchenne muscular dystrophy (Kunkel, 1986).
The muscle cells of these patients do not contain dystrophin and as a result, their muscles become considerably weaker and smaller over time.
Consequently, many patients are confined to a wheelchair by early childhood.
Other important examples of proteins with struc- tural roles includecollagen, which gives our skin and bones structure, andkeratin, which forms the structural basis of hair and nails.
Immunological
Antibodies are proteins produced by cells of the immune system and they play an important role in fighting against infections. These proteins rec- ognize and neutralize foreign substances (i.e. anti- gens) such as bacteria and viruses, etc. through the process of phagocytosis. Due to this impor- tant role of fighting infection, it is crucial that we
obtain enough protein in our diet so that we can consistently manufacture the appropriate supply of antibodies. When we are vaccinated for common diseases such as influenza and measles, etc. we are actually being injected with a small amount of the dead or inactive virus, which causes our bodies to make the corresponding proteins (antibodies) so that we can mount an effective immune response if we contract the disease at a later date.
Regulatory
Proteins known astranscription factorscan bind to the relevant parts of theDNAwithin ourgenes which can ultimately lead to the formation of new proteins. The overall process of gene tran- scription and translation is known as protein synthesis and, because of its importance to sport and exercise metabolism, we outline the stages involved in this process later in this chapter.
Table 4.1 Amino acid names and their abbreviations
Amino acid name Essential or 3-letter 1-letter
non-essential abbreviation abbreviation
Alanine non-essential Ala A
Arginine non-essential Arg R
Asparagine non-essential Asn N
Aspartate non-essential Asp D
Cysteine non-essential Cys C
Glutamate non-essential Glu E
Glutamine non-essential Gln Q
Glycine non-essential Gly G
Histidine non-essential His H
Isoleucine essential Ile I
Leucine essential Leu L
Lysine essential Lys K
Methionine essential Met M
Phenylalanine essential Phe F
Proline non-essential Pro P
Serine non-essential Ser S
Threonine essential Thr T
Tryptrophan essential Trp W
Tyrosine non-essential Tyr Y
Valine essential Val V