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METABOLISM AND ENERGETICS

INTRODUCTION

A Brief Review of Cellular Metabolism

1. Glucose catabolism in the cytoplasm produces two molecules of pyruvic acid and 2 molecules of ATP. In aerobic glycolysis the pyruvic acid molecules enter the mitochondria, where they are broken down completely.

2. The carbon and oxygen atoms are lost as carbon dioxide, and the hydrogen atoms are passed to coenzymes that deliver them to the electron transport system. The electron transport system generates ATP and the hydrogens combine with oxygen to form water under controlled conditions.

3. Gluconeogenesis can occur using any of the compounds involved in the cytoplasmic reactions of glycolysis. By interconversion the body can synthesize the other carbohydrates needed to produce glycogen, carbohydrate complexes, or nucleic acids.

4. Triglycerides in the cytoplasm are broken down to fatty acids and glycerol. The glycerol enters the glycolytic pathways, and the fatty acids enter the mitochondria.

5. Beta oxidation breaks fatty acids into molecules of acetyl-CoA that can be used in the Krebs cycle.

6. The steps of beta oxidation cannot be reversed, and the body cannot manufacture all of the fatty acids needed for normal metabolic operations.

7. Proteins in the cytoplasm are broken down to amino acids, and the amino acids enter the mitochondria.

8. In the mitochondria the amine groups are removed, and the carbon skeleton converted to one of the compounds involved in glycolysis.

9. The body cannot synthesize all of the amino acids needed for protein synthesis.

METABOLIC INTERACTIONS

1. The liver represents the focal point for metabolic regulation and control.

2. Adipose tissue stores lipids, primarily as triglycerides.

3. Skeletal muscle maintains substantial glycogen reserves, and the contractile proteins can be mobilized and the amino acids used as an energy source.

4. Neural tissue depends on aerobic glycolysis for energy production, and does not contain energy reserves.

5. Other peripheral tissues are able to metabolize glucose, fatty acids, or other substrates under the direction of the endocrine system.

The Absorptive State

1. The absorptive state continues for around 4 hours after each meal. During this period nutrients are entering the blood as intestinal absorption proceeds.

The Liver:

1. The liver closely regulates the glucose content of the blood arriving over the hepatic portal vein.Plasma glucose concentrations normally range from 90-120 mg%.The glucose removed from the blood can be stored as glycogen.

2. The liver regulates the amino acid composition of the blood within the range of 35-65 mg%.

3. The liver cells can manufacture lipids from excess glucose or amino acids.

Adipose Tissue:

1. Lipemia often marks the absorptive state.Circulating triglycerides are freed from chylomicrons and broken down by lipoprotein lipase found on the inner surfaces of endothelial cells in adipose tissue, skeletal muscle, cardiac muscle, and the liver.

Skeletal Muscle, Neural Tissue & Peripheral Tissues:

1. During the absorptive state glucose molecules are catabolized and amino acids are used to build proteins. Skeletal muscles may also catabolize circulating fatty acids, and the energy is used to increase glycogen reserves.

The Postabsorptive State

1. The postabsorptive state extends from the absorptive state to the next meal.

The Liver and Gluconeogenesis:

1. When blood glucose falls, the liver begins breaking down glycogen reserves and releasing the glucose into the circulation.

2. As the duration of the fast increases, gluconeogenesis accelerates.

3. The glycerol produced by the hydrolysis of triglycerides can be used for energy production or for gluconeogenesis. The fatty acids undergo beta oxidation; the fragments enter the Krebs cycle or combine to form ketone bodies.

4. Ketone bodies enter the circulation and diffuse to peripheral tissues. There the compounds are reconverted to acetyl-CoA and catabolized in the Krebs cycle.

5. Glucogenic amino acids can be converted to pyruvic acid and used for gluconeogenesis. Ketogenic amino acids can be converted to cetyl-CoA, and these are either catabolized or converted to ketone bodies.

6. The liver performs the deamination reactions needed to catabolize amino acids, and the urea concentration of the blood rises as the postabsorptive state continues.

Adipose tissue:

1. Adipose tissue contains a 1-2 month energy reserve. Adipose deposits are found in the hypodermis, the greater omentum, between muscles, and packed around the kidneys and gonads.

2. During the postabsorptive state, lipolysis increases and the fatty acids are released into the circulation for catabolism by peripheral tissues and the liver.

Skeletal muscle:

1. Skeletal muscles metabolize ketone bodies and breakdown glycogen reserves. Lactic acid is generated, and it diffuses into the bloodstream. After a prolonged fast, cathepsins begin breaking down contractile proteins and the amino acids diffuse into the circulation.

Other Peripheral Tissues:

1. Peripheral tissues metabolize ketone bodies and fatty acids instead of glucose.

Neural tissue:

1. Business continues as usual, with a reliance upon glucose as an energy source until blood glucose levels get extremely low.

Adjustments to Starvation

1. During starvation carbohydrate reserves are exhausted almost immediately.

2. Lipid catabolism meets most of the energy demands of

peripheral tissues during the weeks that follow, but as the fast continues protein catabolism becomes increasingly important.

3. When lipid reserves are exhausted, crises follow as contractile and structural proteins are mobilized.

DIET AND NUTRITION

1. Nutrition refers to the assimilation of nutrients from the diet. Nutritionists attempt to ensure that a given diet meets the particular metabolic needs of an individual.

The Four Basic Food Groups

1. A balanced diet contains all of the ingredients necessary to maintain homeostasis. Failure to maintain a balanced diet eventually leads to malnutrition. A balanced diet includes adequate substrates for energy production, essential amino and fatty acids, minerals, water, and vitamins.

Nitrogen Balance:

1. Amino acids, purines, pyrimidines, and creatine contain nitrogen atoms, and they constitute the N compounds of the body.

2. Nitrogen reserves are minimal, and a continual dietary supply must be provided to meet the demands of metabolic turnover.

Minerals, Vitamins, and Water

Minerals and Vitamins:

1. Minerals act as cofactors, they contribute to the osmolarity of body fluids, and they play a role in transmembrane potentials, action potentials, the construction and maintenance of the skeleton, the transport of gases, buffer systems, fluid absorption, and waste removal.

2. The body contains significant mineral reserves, primarily in the skeleton.

3. Vitamins are needed in very small amounts. Vitamins A, D, E, and K are fat-soluble vitamins. Fat-soluble vitamins taken in excess may cause hypervitaminosis because they are stored rather than excreted.

4. The water-soluble vitamins are not stored, and excess vitamins are usually excreted in the urine. In the absence of adequate dietary supplies, avitaminosis may develop.

Water:

1. Water is obtained from food, drink, and through metabolic generation.

2. If less food is consumed, fluid intake must be increased to provide the water normally found in food. As lipid and protein catabolism increases, water losses increase as nitrogenous wastes enter the urine.

Diet and Disease

1. A balanced diet can improve general health. Most Americans eat too much and consume too many fats, including cholesterol, too many sugars, and an excess of sodium ions.

BIOENERGETICS

1. Calorimetry measures the amount of energy contained in the bonds of organic molecules. The measurements are taken using a calorimeter. The energy content of food is usually expressed in terms of Calories per gram.

2. A gram of lipid releases roughly twice as many Calories as a gram of either proteins or carbohydrates.

3. Less than half of the energy contained in food can be captured as ATP through metabolic processes.

4. The efficiency of the glycolytic steps in the cytoplasm averages roughly 28 percent, while that of the entire process of aerobic glycolysis averages about 42 percent.

5. The rate of Calorie utilization per unit time represents the metabolic rate of an individual. The basal metabolic rate is the rate of energy utilization at rest.

Thermoregulation

1. The energy released but not captured during metabolic reactions warms the surrounding tissue. The homeostatic regulation, of body temperature is known as thermoregulation.

Mechanisms of heat transfer:

1. Heat is continually being produced because metabolic operations are inefficient.

2. Thermoregulation consists of conserving that heat or losing it to the external environment. Radiation, conduction, convection, and evaporation are used to gain or lose heat.

3. The preoptic area of the hypothalamus acts as the body's thermostat. It's output controls the heat-loss center and the heat gain center.

Mechanisms for Increasing Heat Loss

1. Heat loss occurs through peripheral vasodilation, perspiration, and increased evaporation rates at the lungs. The sensation of being overly warm leads to behavioral adjustments that reduce additional heat gains.

Mechanisms for Promoting Heat Gain:

1. Responses that reduce heat loss may include peripheral vasoconstriction, countercurrent heat exchange, and behavioral changes. Heat gain may occur due to shivering or nonshivering thermogenesis.

Sources of Individual Variation:

1. Individuals vary with respect to their metabolic and thermoregulatory demands. Important sources of variation include acclimatization, body size, age, tissue distribution, surface to volume ratios, differences in the normal values accepted by the preoptic area, and dietary composition.

Fevers:

1. Pyrexia, or fevers, occur when the body temperature is maintained above 37.2o C (99o F). They may result from abnormalities of the thermoregulatory mechanism or in response to pathological conditions or circulating pyrogens.

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