Following chemical changes take place during contraction in the anaerobic and aerobic phases in human body.
1. Glycolysis and Oxidative Breakdown:
This process involves many separate enzymes and different intermediates. The end products are pyruvic or lactic acid. The first step in the liberation of energy for contraction is the breakdown of glycogen in the muscle fibre. The glycogen reacts with inorganic phosphate and splits up into glucose-1-phosphate (Cori ester) with the help of phosphorylase. Muscle phosphorylase contains pyridoxal phosphate as a cofactor.
The process of uptake of the phosphate and its cleavage into glucose phosphate is called phosphorolysis. Glucose-1-phosphate is converted into glucose-6-phosphate. Glucose-6- phosphate is changed into fructose-6-phosphate, then into fructose-1, 6-diphosphate and into two triose phosphates. The triose phosphate is finally converted into pyruvic acid (Fig. 6.12).
Pyruvic acid is reduced to lactic acid by reduced nicotinamide adenine dinucleotide (NAD.2H) [previously called reduced coenzyme-1 or DPNH2] and lactic dehydrogenase in the absence of oxygen. Out of the total quantity of the lactic acid formed under anaerobic conditions one-fifth of it is oxidized to CO2 and H2O and four-fifths are re-synthesised into glycogen in the liver. In the presence of oxygen the pyruvic acid is oxidized through a series of steps known as the Krebs tricarboxylic acid (TCA) cycle.
In this cycle one molecule of pyruvic acid loses one molecule of CO2 and is converted into active acetate (Acetyl coenzyme-A). The active acetate is metabolised through a series of reactions known as citric acid cycle (described under Carbohydrate Metabolism). Each molecule of pyruvic acid at each turn of the cycle liberates three molecules of CO2 and two molecules of water.
There is net production of 39 ATP per one hexose unit of glycogen metabolised. But per oxidation of one molecule of glucose into CO2, and water 38 ATP are produced. In anaerobic condition only 2 ATP are produced per molecule of glucose metabolised and 3 ATP are produced per hexose unit of glycogen metabolised under such condition.
Energy for muscular contraction is thus provided as ATP from- (a) Anaerobic glycolysis leading to breakdown of glycogen and glucose to pyruvic and lactic acids, (b) Oxidation of lactic acid to pyruvic acid and further oxidation of pyruvic acid in TCA cycle via acetyl CoA into H2O and CO2, (c) Fatty acid oxidation through β-oxidation and through TCA cycle also provides some amount of ATP as muscle energy, and (d) During muscular activity creatine phosphate also maintains the ATP level of the muscle.
2. Role of Creatine Phosphate or Phosphagen and Adenosine Triphosphate (ATP):
Creatine phosphate (CrPO4) plays an essential role in the muscular contraction. The role of carbohydrate metabolism is to provide energy for the re-synthesis of creatine phosphate. The breakdown process of creatine phosphate Fig. 6.12 involves the re-synthesis of ATP. Creatine phosphate reacts with ADP and as a result of which creatine phosphate loses its phosphate radical and ATP is formed.
ATP is again broken down by adenosine triphosphatase (ATP-ase) to form ADP and inorganic phosphate. The breakdown of ATP precedes that of creatine phosphate. ATP is composed of adenine, d-ribose and 3-molecules of orthophosphate. The energy-rich phosphate bonds are contained in creatine phosphate and ATP, and this bond is indicated by a symbol ‘∼’ in their formulae. The terminal phosphate group which is split off from ATP or the phosphate bond energy may be transferred to other compound, e.g., in the conversion of fructose-6-phosphate into fructose-1, 6-diphosphate and ADP is formed.
The re-synthesis of creatine phosphate takes place with the help of phosphate released from ATP in a reversible reaction. As a result of transference of phosphate, ATP changes into ADP. Creatine phosphate also serves as a reserve source of phosphate bond energy for rapid re-synthesis of ATP in case of muscle poisoned with the iodo-acetic acid. In the iodo-acetate poisoned muscle the carbohydrate breakdown is inhibited but re-synthesis of ATP can take place for a considerable period with the help of creatine phosphate.
The sequence of events may be summarised in the following order:
(1) ATP breaks down into ADP and there is release of phosphate and energy. Actin and myosin are the contractile substances. ATP helps in the shortening of actomyosin threads.
(2) Creatine phosphate breaks down and the phosphate with its energy is transferred to ADP and forms ATP. The creatine phosphate store is thus a constant supplier of ATP.
(3) Glycogen of the muscle breaks down in a series of stages and releases energy-rich phosphate bond in the intermediate stages which in turn help in the re-synthesis of ATP and also of re-synthesis of creatine phosphate.
Under anaerobic conditions glycogen breakdown occurs as far as pyruvic acid, which again takes up hydrogen from NAD.2H and changes into lactic acid. A dehydrogenase catalyses this reaction which is reversible. Muscle glycogen is formed from this lactate by a process known as Cori cycle.
Under aerobic conditions lactic acid is also produced. It diffuses out into the circulation and other body fluids. It is re-oxidised into the pyruvic acid mainly in the liver and enter the citric acid cycle or may be transformed into glycogen.
3. Muscular Contraction and Its Relationship with the Breakdown of ATP:
The mechanism of muscular contraction begins into the breakdown of ATP. The contraction takes place due to release of phosphate bond energy from ATP. When the muscle is stimulated the impulse travelling over the fibre is associated with an increase in sodium and calcium permeability of the membrane.
As a result, inflow of sodium ions to the inside of the muscle fibre is accompanied by a slight inflow of calcium ions at the same time. The calcium ion then stimulates adenosine triphosphatase (ATP-ase) which helps in the release of energy from ATP surrounding the muscle filaments.
The energy produces momentarily an electrostatic charge between the actin and myosin filaments which in turn pulls the actin filaments into the spaces between the myosin filaments. ATP-ase remains in an activated state so long calcium ions are present inside the muscle fibre.
Surrounding the filaments and sarcoplasmic reticulum there is another substance known as relaxing substance which binds calcium ions within a fraction of a second after they enter the interior of the fibre so that the calcium is changed into unionised form. As a result of inactivation of calcium ions in the interior of the muscle fibre no more energy is released from adenosine triphosphate. The electrostatic charges between the actin and myosin filaments disappear, thus allowing the muscle to relax.
4. Utilisation of Other Fuels during Muscular Contraction:
It is possible that skeletal muscle also utilizes ketone bodies and free fatty acids for the re-synthesis of ATP. This is particularly applicable in the case of flight muscles of migratory birds, where glycogen store is not sufficient to supply energy for a long period of muscular contraction.
Cardiac muscle is similar to the above flight muscle, biochemically, and consumes ketone bodies and free fatty acids in harmony with them for continued activity.
5. Changes in H-Ion Concentration:
The normal reaction of muscle is slightly on the alkaline side (pH 7.3). During muscular activity both acid and alkaline products are formed. These compounds try to neutralise each other and thereby prevent any serious change of reaction. Besides this, the muscles possess an efficient buffer system in the form of muscle proteins, their Na-and K-salts, the inorganic phosphate, the bicarbonates, etc., all of which help to prevent marked change of muscle pH.
But in spite of this, in the initial stages the reactions become more alkaline due to the liberation of free creatine (which is strongly alkaline). In prolonged activity, especially under inadequate oxygen supply, the reaction becomes distinctly acid (pH about 6.0) due to accumulation of lactic acid.
6. Other Chemical Changes:
In the resting muscle the R.Q. varies from 0.85 to 0.90, showing that the resting metabolism involves the oxidation of certain non-carbohydrate foodstuff. Hill, by determining the osmotic pressure of the muscle under various conditions, has proved that, unknown reactions of considerable magnitude other than carbohydrate oxidation, take place. It has also been shown that glycerol, ketones, etc., may join the path of glycogen metabolism and undergo a process of oxidation.
Moreover, little is known about the changes seen in the nitrogenous constituents of muscles, such as carnosine, inositol, free creatine, etc. All these indicate that muscles utilise not only carbohydrates but other substances as well.
7. Oxygen Utilisation and CO2 Production:
The broad facts about this are as follows:
(a) The resting muscle uses O2 and liberates CO2, the R.Q. being 0.85- 0.90.
(b) O2 is not required for contraction and lactic acid formation. The muscle maintains its irritability and contractility for a good length of time even under complete anaerobic conditions, and
(c) Oxygen is essential during recovery process when lactic acid burns and glycogen is re-synthesised. The R.Q. of this period is unity.
8. Cori Cycle:
In the living body under normal conditions, the oxygen supply to the muscles is so efficient that slight or moderate exercise does not produce lactic acid accumulation. Because due to ready oxygen supply, lactic acid quickly disappears. But in heavy exercise, the oxygen supply becomes inadequate; excess of lactic acid accumulates in the muscle fibres and diffuses out into the blood stream.
A considerable amount of this blood lactate is utilised by the heart and small amounts by other tissues. A little portion of it may reenter the muscle to form glycogen. But the major part of the blood lactate is taken up by the liver and is converted into glycogen.
Liver can prepare glycogen from lactic acid more quickly than it is done by the muscle. This liver glycogen is converted into glucose, which enters blood stream, and then into the depleted muscles and is concerted into glycogen. The muscle can form glycogen more readily from glucose than it is done by the liver. In this way the muscle gains back its depleted glycogen store. Liver and muscle help each other to organise a bigger cycle through which lactic acid moves.
This cycle is as follows:
Muscle glycogen → Muscle lactic acid → Blood lactate → Liver glycogen ⇋ Blood glucose → Muscle glycogen. This cycle is called the Cori cycle (Fig. 6.14).
