Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemical Foundations of Human Vital Activity
Integration and Regulation of Metabolism as the Biochemical Basis of Adaptation Processes
The Role of Individual Tissues in the Integration of Intermediary Metabolism

Almost all Tissues contain the Enzymes required for the Catabolism of CARBOHYDRATES, fats, and Proteins, as well as for energy production. However, they also possess specific biochemical processes that influence METABOLISM in other tissues. Let us examine the involvement of such vital tissues as the Liver, skeletal Muscles, Heart, and Brain in the integration of protein, fat, and Carbohydrate Metabolism.

The Role of the liver. This organ plays a central role in distributing nutrients among other tissues (Fig. 111). It carries out the Biosynthesis OF GLUCOSE (via Gluconeogenesis), Fatty acids, and Ketone Bodies, as well as proteins that are subsequently transported via the bloodstream to other tissues. The liver helps maintain constant Blood glucose levels through Glycogen reserves, participates in The breakdown of fats during Digestion, and detoxifies drugs, preservatives, Hormones, and other xenobiotics. Nutrients enter the liver from the Small Intestine via the PORTAL VEIN SYSTEM. Here, they undergo further transformations or re-enter the bloodstream to be distributed among tissues According to the body's physiological demands.

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Fig. 111 The role of individual tissues in the integration of metabolism

Glucose entering from the intestine is phosphorylated with the participation of ATP and the enzyme hexokinase, converting into glucose-6-phosphate. This form of glucose can undergo transformations via five distinct pathways:

✵ it can be dephosphorylated and released into the blood, maintaining a constant glucose level;  

✵ it can be used for the synthesis or replenishment of liver glycogen;

✵ it can be utilized for fat synthesis;

✵ it can be oxidized via Glycolysis or aerobically to supply ATP and heat (although the liver primarily utilizes fats for its energy needs);

✵ it can be oxidized in the Pentose Phosphate Pathway to supply pentoses for nucleotide synthesis and NADH₂ for fat biosynthesis.

During gluconeogenesis, the liver utilizes not only fats and Amino Acids but also lactic acid to synthesize glucose. Lactic acid accumulates in skeletal muscles during intense muscular work as a product of glycolysis. However, its oxidation and conversion into glucose occur predominantly in the liver. Thus, the liver participates in normalizing the body's acid-base balance and helps restore blood glucose levels, as well as glycogen reserves in muscles during rest, since the glucose synthesized in the liver is transported via the bloodstream to skeletal muscles (see Chapter 9). According to recent studies, the major portion of lactic acid (up to 75%) is aerobically oxidized in various tissues, providing energy for the resynthesis of energy substrates. A smaller portion (20%) is converted into glucose in the liver. Nevertheless, this tissue-level Metabolic Integration (muscles — liver) plays a crucial role in replenishing depleted carbohydrate reserves after heavy physical exertion.

The liver plays a vital role in the metabolism and redistribution of Lipids, as it synthesizes fatty acids, Phospholipids, Cholesterol, and ketone bodies. These ketone bodies are then released into the blood and taken up by skeletal muscles, The Heart, and—under conditions of starvation or prolonged physical exertion—by the brain, where they are metabolized in The Citric Acid Cycle to generate ATP energy.

The role of skeletal muscles. Metabolism in skeletal muscles is directed toward generating energy for contraction and relaxation processes, The amount of which varies dramatically depending on their activity level. The primary energy substrates for muscles are glucose, fatty acids, and ketone bodies. Glucose is stored as glycogen (accounting for about 2% of Muscle mass), which can rapidly break down into glucose-6-phosphate and be oxidized via glycolysis (see Chapter 9). Due to the absence of the enzyme glucose-6-phosphatase, glucose-6-phosphate cannot be converted into free glucose and released into the blood, unlike in the liver. Therefore, muscle carbohydrates are used strictly for their own localized needs.

In resting muscles and during moderate-intensity work, the energy substrates are free fatty acids, ketone bodies, and glucose, which are delivered from the liver via the blood and taken up by the muscles. They are oxidized through aerobic processes, which account for the consumption of about 30% of the oxygen entering the body.

During intense physical work, the demand for ATP surges. Aerobic processes cannot fully meet this demand, even though muscle oxygen consumption increases up to 90% of the body's total intake. Anaerobic mechanisms of ATP generation are then engaged through The Use of creatine phosphate and glycogen reserves (see Chapter 15). Muscle glycogen supplies energy solely via The Glycolytic Pathway. This process produces lactic acid, which is either partially oxidized within the muscles or released into the bloodstream and transported to the liver for gluconeogenesis. The accumulation of lactic acid in muscles lowers the pH and reduces the Efficiency of Energy processes. Glucose is not synthesized in muscles; instead, it is supplied from the liver via the bloodstream and utilized to replenish glycogen reserves (see Fig. 110).

When muscles adapt to physical loads, their energy potential increases first and foremost, adaptive Protein Synthesis processes are enhanced, and the mechanisms of neural and endocrine REGULATION OF METABOLISM are refined.

The role of the heart muscle. The myocardium operates predominantly under aerobic conditions. It contains a high density of Cell/35.html">Mitochondria, which occupy about 40% of the Cytoplasm volume. The substrates used for oxidation include fatty acids, ketone bodies, pyruvic and lactic acids, and glucose. The heart muscle stores virtually no glycogen. Due to its aerobic Energy Metabolism, an adequate supply of oxygen is mandatory for the myocardium. Under hypoxic conditions, incompletely oxidized metabolic products accumulate, which can trigger acidosis and impair myocardial contractility.

The role of the brain. The brain accounts for only about 2% of an adult's body weight, yet it consumes over 400 kcal (1680 kJ) of energy per day, representing 20% of the total basal requirement. Energy production processes in the brain proceed under strictly aerobic conditions. It consumes over 20% of the oxygen taken in by the body. As an energy source, the brain normally relies exclusively on glucose. Under relative physiological rest, about 90% of blood glucose is taken up by the brain. Because the brain lacks carbohydrate reserves, it is extremely sensitive to drops in blood glucose levels. The uptake of glucose by Nerve Cells is Insulin-independent. When its concentration drops to 60–40 mg%, hypoglycemic coma ensues, accompanied by a loss of consciousness. During prolonged physical work or starvation, the brain can adapt to utilizing ketone bodies. In this state, enzymes that break down ketone bodies are synthesized in the brain. After three days of fasting, the brain derives about 30% of its energy from ketone bodies, and after 40 days of fasting, this figure rises to 70%. The brain primarily oxidizes beta-hydroxybutyrate, which is produced in the liver. Within this tissue, ATP energy is utilized to transmit nerve impulses along Neurons and across synapses, as well as to maintain ion channel activity and neurotransmitter synthesis.

Review Questions

1. What coordinating factors are involved in mediating adaptive metabolic changes?

2. Under what physiological conditions do carbohydrates convert into fats, and fats into carbohydrates?

3. What is the role of carbohydrates in Protein Catabolism?

4. What is the role of amino acids in carbohydrate metabolism? What are "glucogenic amino acids"?

5. Explain The Essence and significance of tissue metabolic integration.

6. Name the primary regulatory systems governing intrametabolic processes. What is their impact on the body's adaptation to physical exertion?

7. Explain The Nature and Significance of the automatic intracellular regulation system in adaptation processes.

8. What is the role of the hormonal system in the integration of metabolism and The formation of General adaptation syndrome?

9. What pathways of transmitting hormonal effects to intracellular processes do you know?

10. Explain the regulatory effect of The Nervous system on the contractile function of muscles.

11. What is the role of the liver in integrating Intermediary Metabolism across various tissues?

12. What are the characteristics of energy metabolism in skeletal muscles at rest and during physical exertion?

13. What Energy Sources are primary in the heart muscle and the brain?