In this article we will discuss about:- 1. Introduction to Phosphorylation 2. Definition of Phosphorylation 3. Physiological Importance 4. Control.
Introduction to Phosphorylation:
Certain organic phosphates, formed in the tissues out of anabolic chemical reaction, play a key role in the energy transactions of living organisms. The importance of organic phosphates in metabolism was first indicated by the studies of Harden and Young, who found that fermentation of glucose by cell-free yeast juice increased rapidly when inorganic phosphorus is added to the medium, which was later converted to organically bound phosphate.
The work of Embden, Meyerhof, Cori and their associates show that organic phosphates concerned with the metabolism of glucose by yeast are also intermediates in the metabolism of glycogen and glucose in muscle and other tissues.
The presence of ATP, ADP, CP and other high-energy phosphate compounds in the tissue and their participation in different metabolic processes indicate the importance of organic phosphates in metabolism. The sugar phosphates, although not high-energy compounds, are obligatory intermediates. Their formation involves phosphorylation by the high-energy compound ATP in presence of suitable enzymes.
Definition of Phosphorylation:
The term phosphorylation includes all chemical reactions in the body which require combination with phosphoric acid. The reverse changes are called dephosphorylation, where phosphoric acid is dissociated from the compound.
These two processes are probably the reversible reactions of the same enzyme system.
Physiological Importance of Phosphorylation:
Phosphoric acid enters into the composition of cell protoplasm. Hence, phosphorylation is an essential chemical process for all cells. In addition to this it takes an essential part during absorption and metabolism of different foodstuffs.
Its effect in the different channels of metabolism are summarised below:
1. In Relation to Carbohydrates:
i. Absorption of carbohydrates through the intestinal mucosa and also reabsorption of glucose from renal tubules, are helped by phosphorylation. In both the epithelia hexose phosphate is formed. This compound undergoes dephosphorylation, hexose enters the blood stream and phosphoric acid is left behind.
ii. Formation of glycogen from glucose and breakdown of glycogen into glucose in the liver and muscles are believed to take place through the process of phosphorylation.
iii. During chemical changes accompanying muscular contraction, phosphorylation takes place at all important steps. As a matter of fact phosphorylation and dephosphorylation alternately go on in this process. Glycogen is broken down up to lactic acid through a series of phosphorylated compounds.
Breakdown and synthesis of ATP and phosphagen are also the examples of dephosphorylation and phosphorylation. The phosphorylation of carbohydrate metbolites takes place in two stages: In the first stage ADP is phosphorylated by Pi to ATP (Fig. 10.5).
This reaction can take place only in presence of intact oxdation process and the energy-yielding (oxidation) mechanism is coupled with energy-harnessing (phosphorylation) mechanism. Uncoupling agents like 2, 4-dinitrophenol inhibit phosphorylation but not oxidation.
They elevate the oxygen consumption rate. The second stage in phosphorylation process is transfer of phosphate group from ATP to other intermediates. Oxidative phosphorylation takes place in the cristae of the mitochondria (Fig. 10.6).
2. In relation to Fats:
i. During absorption of fats, neutral fats and phospholipids are synthesised in the absorbing epithelium. Phosphorylaton is carried out by the enzyme, phosphorylase.
ii. Liver synthesises phospholipids, specially lecithin. It is a very important step in the transport of fat. It also acts as a primary stage in the further oxidation of fatty acids. Fatty acid oxidation is a function of mitochondria (Fig. 10.7).
iii. Phospholipids enter into the composition of element constant of the cell. Hence, it is essential for cell life. It is believed that each cell can synthesise its own phospholipids locally by a process of phosphorylation.
iv. Kephalin or cephalin, one of the phospholipids, is built up by phosphorylation which initiates blood clotting.
3. In Relation to Proteins:
i. It is an important step by which all the phosphoproteins are synthesized, such as, nucleoproteins, caseinogens, etc.
ii. It is also probable that phosphorylation takes an important part in tissue oxidation during which proteins, fats and carbohydrates are finally broken down.
iii. In relation to vitamin. Some members of the vitamin B group are phosphorylated compounds, e.g., thiamine pyrophosphate, riboflavin phosphate, etc. They are believed to act as coenzymes in the oxidation and reduction processes in the cell.
4. In Relation to Inorganic Salts:
i. Sodium plays an important part in phosphorylation. Its role is described below.
ii. The acid and alkaline phosphates, which should be regarded as phosphorylated compounds, act as a very important buffer system in the body.
iii. The complex interrelation between calcium and phosphorus may be primarily a process of phosphorylation and dephosphorylation.
5. In Relation to Bone Formation:
Formation of bone, i.e., deposition of inorganic phosphoric acid compounds from organic phosphates -is also probably another example of phosphorylation.
Control of Phosphorylation:
The enzymes that take part in this process are phosphorylase, phosphatase, etc.
a. Adrenal cortex is believed to be directly responsible for phosphorylation. Glucocorticoids inhibit phosphorylation adrenalectomy accelerate it.
b. Anterior pituitary, by its adrenocorticotrophic hormone, may exert a superior control on phosphorylation, through adrenal cortex. The marasmic condition that develops in diseases of adrenal cortex may be partly explained by the consequent disturbance of phosphorylation, which affects absorption, metabolism and nutrition of the body. Growth hormone affects phosphorylation in a similar way as glucocorticoids.
iii. Inorganic Salts:
Sodium may have some effects on phosphorylation (see below).
It is believed that adrenal cortex controls phosphorylation by helping the enzymes responsible for the process. But it is also known that many of the defects, seen in diseases of the adrenal cortex, are rectified by giving enough NaCl. For instance, the defective fat absorption in adrenalectomised animals improves by giving NaCl.
It is interesting to note that it is the same adrenal cortex which also controls Na metabolism. From these observations it may be suggested that adrenal cortex controls phosphorylation not by a direct action on the enzymes but by an indirect influence on Na metabolism.
It is also known that phospholipids are antagonistic to cholesterol. These two compounds are always found to remain together. It is also interesting to note that adrenal cortex which controls phosphorylation and therefore phospholipid formation, also controls metabolism of sterols.