Test Questions

1. What is the difference of the terms "water and salt metabolism" and "mineral metabolism"?

2. What are the main parameters of the water environment of the body?

3. Specify the function of microelements in the human body.

4. Describe the excretory function of the kidneys.

5. What is the homeostatic function of the kidneys?

6. What metabolic functions do the kidneys perform?

7. What hormones are involved in the regulation of osmotic pressure and extracellular fluid volume?

8. Describe the mechanism of action of the renin-angiotensin system.

8. Biochemistry of nervous tissue

8.1. Features of metabolism of nervous tissue

Neuron is a central functional cell of the nervous tissue; it is associated with dendrites and axons with the same cells and cells of other types, such as secretory and muscle cells. The cells are separated by synaptic gaps. Communication between cells is accomplished by signal transmission. The signal passes from the cell body along the axon to the synapse. The substance mediator is released in the synaptic gap. The mediator interacts with the receptors on the other side of the synaptic cleft. This provides a perception of the signal, and this generates a new signal in the acceptor cell.

The functions of the nervous tissue include the generation of an electrical signal (nerve impulse), conducting nerve impulses, memorization and storage of information, the formation of emotions and behavior, thinking.

Specificity of neural tissue is determined by the blood-brain barrier (BBB). Blood-brain barrier has selective permeability to various metabolites, and also promotes the accumulation of certain substances in nervous tissue. Thus, the nervous tissue differs from other tissues by chemical composition.

Most of the lipids of nerve tissue are composed of plasma and subcellular membranes of neurons and myelin sheaths. Lipid content is very high in the nervous tissue compared with other tissues in the body. The lipid composition of nervous tissue includes: phospholipids, glycolipids and cholesterol, and there is no neutral fat. Cholesterol esters can be found only in areas of active myelination. Cholesterol is synthesized very intensively only in the developing brain. The activity of HMG-CoA-reductase (a key enzyme in cholesterol synthesis) is low in the adult brain. The content of free fatty acids is very low in the brain.

Functions of lipids of nerve tissue:

1. Structure: lipids are part of the cell membranes of neurons.

2. Function of insulators.

3. Protective. Gangliosides are active antioxidants, lipid peroxidation inhibitors. In the case of the damage of brain tissue, gangliosides contribute to its healing.

4. Regulatory. Phosphatidylinositols are precursors of biologically active substances.

Lipids are constantly regenerated. Some lipids (cholesterol, cerebrosides, phosphatidylethanolamines, sphingomyelins) regenerate slowly, over months and even years. The exception is phosphatidylcholine and, especially, phosphatidylinositols. They regenerate very quickly (days, weeks). Synthesis of cerebrosides and gangliosides proceeds with great velocity in the developing brain during myelination. In adults, almost all of cerebrosides (90%) are in the myelin sheath, and gangliosides are in neurons.

Nerve cells are not divided; therefore, there is no DNA synthesis in them. However, the RNA content in them is the highest compared with the cells of other tissues. The rate of RNA synthesis is also very high. In the cells of nervous tissue pyrimidines cannot be synthesized, as the enzyme carbamoyl phosphate synthetase is absent in nervous tissue. Pyrimidines have to come from the blood: the blood brain barrier is permeable to them. Blood brain barrier is easily permeable for purine mononucleotides, but unlike pyrimidines, they can be synthesized in nervous tissue. In the nervous tissue nucleic acids provide the storage and transmission of genetic information and its implementation in the synthesis of cellular proteins.

For example, strong stimuli – loud sounds and strong visual stimuli and emotions lead to an increase in the rate of synthesis RNA and protein in certain brain regions. This indicates that changes in the nervous system, reflecting the individual experience of the organism, are encoded in the form of synthesized macromolecules. Information by which neurons established only certain connection with certain neurons is encoded in the structure of the polysaccharide chains of membrane glycoproteins. The formation of such bonds, not laid down during embryonic development is the result of the experience of the individual organism, and is the material basis for storing information that defines the behavior of the organism.

The nervous tissue which is only 2% of body weight consumes 20% of the oxygen entering the body, and the energy potential of neural tissue is limited.

Metabolism of carbohydrates. The main pathway for energy is only the aerobic breakdown of glucose. Glucose is almost the only energy substrate coming into the nervous tissue, which can be used in the cells to form ATP. Penetration of glucose into the brain does not depend on insulin action, which does not penetrate the blood-brain barrier. Effect of insulin is manifested only in the peripheral nerves. The content of glycogen in the nerve tissue is negligible and can not provide the brain with energy even for a short time. On the other hand, the oxidation of non-carbohydrate substrates for energy does not occur. Therefore, during hypoglycemia and / or short-term hypoxia in neural tissue a small amount of ATP is formed. The consequence is a rapid onset of coma and irreversible changes in the brain tissue.

High velocity of glucose consumption by nerve cells is ensured primarily by the work of highly active hexokinase of the brain. Unlike other tissues, hexokinase is not a key enzyme of all the pathways of glucose metabolism. The key enzymes are phosphofructokinase and isocitrate dehydrogenase.

The formation of NADPH₂, which is used in the nerve tissue mainly for the synthesis of fatty acids and steroids, is provided by a relatively high rate of the pentose phosphate pathway of glucose breakdown.

The functioning of the nervous tissue is accompanied by rapid changes in the use of energy. The sharp increase in energy occurs at a very rapid transition from sleep to wakefulness. During sleep, creatine is stored. The transition to wakefulness leads to a sharp decrease in the concentration of ATP. The formation of ATP from creatine phosphate is observed.

The metabolism of amino acids and proteins. Brain tissue rapidly exchanges amino acids with the blood. There are special transport systems – two for the uncharged amino acids and several more – for amino acids, positively and negatively charged. Up to 75% of the total number of amino acids of nervous tissue are aspartate and glutamate, as well as their transformation products or substances, synthesized with their participation (glutamine, acetyl derivatives, glutathione, GABA, etc.). Their concentrations and, above all, the concentration of glutamate in nervous tissue are very high. For example, the concentration of glutamic acid can reach 10 mmole/l.

Glutamic acid is associated with a large number of reactions with the intermediate metabolites of the TCA cycle (energy function). Glutamate (together with aspartate) is involved in the reactions of deamination of other amino acids and temporary neutralization of ammonia. Neurotransmitter GABA is formed from glutamate. It is involved in the synthesis of glutathione – a component of the antioxidant system.

Glutamate is formed from its keto analog – α-ketoglutaric acid in the reaction of transamination. The large expenditure of α-ketoglutaric acid is compensated by conversion of aspartic acid metabolite in the TCA cycle – oxaloacetate.

Formed from glutamate, GABA as a result of several reactions can be converted back to oxaloacetate. By this way GABA shunt is formed, which is available in the tissues of the brain and spinal cord. Therefore, in these tissues, the contents of GABA, an intermediate metabolite of the cyclic process, are significantly higher than in the rest. The formation of GABA is used up to 20% of the total amount of glutamate.

The remaining pathways of amino acids metabolism are similar to those existing in other tissues. Brain tissue is able to synthesize amino acids, as well as other tissues. Heretofore there is incomprehensible the presence of almost full set of enzymes of ornithinic cycle, does not containing carbamoyl phosphate synthetase, in the brain; because of which the urea is not formed.