Regulation of Organic Metabolism Growth and Energy Balance

Regulation of Organic Metabolism, Growth and Energy Balance

§ Nutrient – a substance that promotes normal growth, and maintain various activities of human body. § Major nutrients – carbohydrates, lipids, and proteins

Absorptive and Post-absorptive States § Metabolic controls equalize blood concentrations of nutrients between two states Absorptive During which ingested nutrients are entering the blood from the gastrointestinal tract. The time during and shortly after nutrient intake Post-absorptive During which the gastrointestinal tract is empty of nutrients and energy must be supplied by the body’s own stores. The time when the GI tract is empty Energy sources are supplied by the breakdown of body reserves

Absoprtive State § The major metabolic thrust is anabolism and energy storage § Amino acids become proteins § Glycerol and fatty acids are converted to triglycerides § Glucose is stored as glycogen § Dietary glucose is the major energy fuel § Excess amino acids are deaminated and used for energy or stored as fat in the liver

Absoprtive State

Principal Pathways of the Absorptive State § In muscle: § Amino acids become protein § Glucose is converted to glycogen § In the liver: § Amino acids become protein or are deaminated to keto acids § Glucose is stored as glycogen or converted to fat

Principal Pathways of the Absorptive State § In adipose tissue: § Glucose and fats are converted and stored as fat § All tissues use glucose to synthesize ATP

Principal Pathways of the Absorptive State

Insulin Effects on Metabolism § Insulin controls the absorptive state and its secretion is stimulated by: § Increased blood glucose § Elevated amino acid levels in the blood § Gastrin, (hormone that stimulate HCl secretions) CCK (cholecystokinin; facilitating digestion within the small intestine), and secretin (hormone that regulates water homeostasis throughout the body) § Insulin enhances: § Active transport of amino acids into tissue cells § Facilitated diffusion of glucose into tissue

Insulin Effects on Metabolism

Diabetes Mellitus § A consequence of inadequate insulin production or abnormal insulin receptors § Glucose becomes unavailable to most body cells § Metabolic acidosis, protein wasting, and weight loss result as fats and tissue proteins are used for energy

Post-absorptive State § The major metabolic thrust is catabolism and replacement of fuels in the blood § Proteins are broken down to amino acids § Triglycerides are turned into glycerol and fatty acids § Glycogen becomes glucose § Glucose is provided by glycogenolysis and gluconeogenesis § Fatty acids and ketones are the major energy fuels § Amino acids are converted to glucose in the liver

Postabsorptive State

Principle Pathways in the Postabsorptive State § In muscle: § Protein is broken down to amino acids § Glycogen is converted to ATP and pyruvic acid (lactic acid in anaerobic states)

Principle Pathways in the Postabsorptive State § In the liver: § Amino acids, pyruvic acid, stored glycogen, and fat are converted into glucose § Fat is converted into keto acids that are used to make ATP § Fatty acids (from adipose tissue) and ketone bodies (from the liver) are used in most tissue to make ATP § Glucose from the liver is used by the nervous system to generate ATP

Principle Pathways in the Postabsorptive State

Hormonal and Neural Controls of the Postabsorptive State § Decreased plasma glucose concentration and rising amino acid levels stimulate alpha cells of the pancreas to secrete glucagon (the antagonist of insulin) § Glucagon stimulates: § Glycogenolysis and gluconeogenesis § Fat breakdown in adipose tissue § Glucose sparing

Hormonal and Neural Controls of the Postabsorptive State In response to low plasma glucose, the sympathetic nervous system releases epinephrine, which acts on the liver, skeletal muscle, and adipose tissue to mobilize fat and promote glycogenolysis

Liver Metabolism § A brief summary of liver functions § Packages fatty acids to be stored and transported § Synthesizes plasma proteins § Forms nonessential amino acids § Converts ammonia from deamination to urea § Stores glucose as glycogen, and regulates blood glucose homeostasis § Stores vitamins, conserves iron, hormones, and detoxifies substances degrades

Cholesterol § Is the structural basis of bile salts, steroid hormones, and vitamin D § Is transported to and from tissues via lipoproteins § Lipoproteins are classified as: (that enable fats & cholesterol to move within the water-based solution of the bloodstream § HDLs – high-density lipoproteins have more protein content § LDLs – low-density lipoproteins have a considerable cholesterol component § VLDLs – very low density lipoproteins are mostly triglycerides

Cholesterol

Lipoproteins v. The liver is the main source of VLDLs, which transport triglycerides to peripheral tissues (especially adipose). v. LDLs transport cholesterol to the peripheral tissues and regulate cholesterol synthesis. v. HDLs transport excess cholesterol from peripheral tissues to the liver. v. Also serve the needs of steroid-producing organs (ovaries and adrenal glands).

Lipoproteins § High levels of HDL are thought to protect against heart attack (Good cholesterol). § High levels of LDL (bad cholesterol), especially lipoprotein (a), increase the risk of heart attack § The liver cholesterol: produces § At a basal level of cholesterol regardless of dietary intake § Via a negative feedback loop involving serum cholesterol levels § In response to saturated fatty acids

Plasma Cholesterol Levels § Fatty acids regulate excretion of cholesterol § Unsaturated fatty acids enhance excretion § Saturated fatty acids inhibit excretion § Certain unsaturated fatty acids (omega-3 fatty acids, found in cold-water fish) lower the proportions of saturated fats and cholesterol

Non-Dietary Factors Affecting Cholesterol § Stress, cigarette smoking, and coffee drinking increase LDL levels § Aerobic exercise increases HDL levels § Body shape is correlated with cholesterol levels § Fat carried on the upper body is correlated with high cholesterol levels § Fat carried on the hips and thighs is correlated with lower levels

Body Energy Balance § Bond energy released from catabolized food must equal the total energy output § Energy intake – equal to the energy liberated during the oxidation of food § Energy output includes the energy: § Immediately lost as heat (about 60% of the total) § Used to do work (driven by ATP) § Stored in the form of fat and glycogen

Body Energy Balance § Nearly all energy derived from food is eventually converted to heat § Cells cannot use this energy to do work, but the heat: § Warms the tissues and blood § Helps maintain the homeostatic body temperature § Allows metabolic reactions to occur efficiently

Regulation of Food Intake § When energy intake and energy outflow are balanced, body weight remains stable § The hypothalamus releases peptides that influence feeding behavior § Orexins are powerful appetite enhancers § Neuropeptide Y causes a craving for carbohydrates § Galanin produces a craving for fats § Glucagon-like peptide-1 (GLP-1) and serotonin make us feel full and satisfied

Feeding Behaviors § Feeding behavior and hunger depend on one or more of five factors § Neural signals from the digestive tract § Blood-borne signals related to the body energy stores § Hormones, § body temperature, and § psychological factors

Nutrient Signals Related to Energy Stores § High plasma levels of nutrients that signal depressed eating § Plasma glucose levels § Amino acids in the plasma § Fatty acids and leptin (hormone that regulating energy intake and expenditure)

Hormones, Temperature, and Psychological Factors § Glucagon and epinephrine stimulate hunger § Insulin and cholecystokinin depress hunger § Increased body temperature may inhibit eating behavior § Psychological factors that have little to do with caloric balance can also influence eating behaviors

Metabolic Rate § Rate of energy output (expressed per hour) equal to the total heat produced by: § All the chemical reactions in the body § The mechanical work of the body § Measured directly with a calorimeter or indirectly with a respirometer

Metabolic Rate § Basal metabolic rate (BMR): The rate of energy expenditure by humans and other animals at rest. Reflects the energy the body needs to perform its most essential activities § Total metabolic rate (TMR) § Total rate of kilocalorie consumption to fuel all ongoing activities

Factors that Influence BMR § Surface area, age, gender, stress, and hormones § As the ratio of surface area to volume increases, BMR increases § Males have a disproportionately high BMR § Stress increases BMR § Thyroxine increases oxygen consumption, cellular respiration, and BMR

Regulation of Body Temperature § Body temperature – balance between heat production and heat loss § At rest, the liver, heart, brain, and endocrine organs account for most heat production § During vigorous exercise, heat production from skeletal muscles can increase 30– 40 times § Normal body temperature is 36. 2 C (98. 2 F); optimal enzyme activity occurs at this temperature § Temperature spikes above this range denature proteins and depress neurons

Regulation of Body Temperature

Core and Shell Temperature § Organs in the core (within the skull, thoracic, and abdominal cavities) have the highest temperature § The shell, essentially the skin, has the lowest temperature § Blood serves as the major agent of heat transfer between the core and shell § Core temperature remains relatively constant, while shell temperature fluctuates substantially (20 C– 40 C)

Mechanisms of Heat Exchange Radiation – it is the process by which the surfaces of all objects constantly emit heat in the form of electromagnetic waves. Conduction – is the loss or gain of heat by transfer of thermal energy during collisions between adjacent molecules. (transfer of heat by direct contact) § Convection – transfer of heat to the surrounding air § Evaporation – heat loss due to the evaporation of water from the lungs, mouth mucosa, and skin (insensible heat loss).

Role of the Hypothalamus § The main thermoregulation center is the preoptic region of the hypothalamus § The heat-loss and heat-promoting centers comprise thermoregulatory centers § The hypothalamus: § Receives input from thermoreceptors in the skin and core § Responds by initiating appropriate heat-loss and heat-promoting activities

Heat-Promoting Mechanisms § Low external temperature or low temperature of circulating blood activates heat-promoting centers of the hypothalamus to cause: § Vasoconstriction of cutaneous blood vessels § Increased metabolic rate § Shivering § Enhanced thyroxine release

Heat-Loss Mechanisms § When the core temperature rises, the heat-loss center is activated to cause: § Vasodilation of cutaneous blood vessels § Enhanced sweating § Voluntary measures commonly taken to reduce body heat include: § Reducing activity and seeking a cooler environment § Wearing light-colored and loose-fitting clothing

Mechanisms of Body Temperature Regulation Chapter 24: Nutrition, Metabolism, and Temperature

Hyperthermia § Normal heat loss processes become ineffective and elevated body temperatures depress the hypothalamus § This sets up a positive-feedback mechanism, sharply increasing body temperature and metabolic rate § This condition, called heat stroke, can be fatal if not corrected

Heat Exhaustion § Heat-associated collapse after vigorous exercise, evidenced by elevated body temperature, mental confusion, and fainting § Due to dehydration and low blood pressure § Heat-loss mechanisms are fully functional § Can progress to heat stroke if the body is not cooled and rehydrated

Fever § Controlled hyperthermia, often a result of infection, cancer, allergic reactions, or central nervous system injuries § White blood cells, injured tissue cells, and macrophages release pyrogens that act on the hypothalamus, causing the release of prostaglandins § Prostaglandins reset the hypothalamic thermostat § The higher set point is maintained until the natural body defenses reverse the disease process

Bone Growth § Growth is a complex process influenced by genetics, endocrine function, and a variety of environmental factors, including nutrition and the presence of infection. The process involves cell division and net protein synthesis throughout the body, but a person’s height is determined specifically by bone growth, particularly of the vertebral column and legs.

Bone is a living tissue consisting of a protein (collagen) matrix upon which calcium salts, particularly calcium phosphates, are deposited. A growing long bone is divided, for descriptive purposes, into the ends, or epiphyses, and the remainder, the shaft.

The portion of each epiphysis that is in contact with the shaft is a plate of actively reproducing cartilage, the epiphyseal growth plate. Osteoblasts, the bone-forming cells at the shaft edge of the epiphyseal growth plate convert the cartilaginous tissue at this edge to bone while new cartilage is simultaneously being laid down in the interior of the plate by cells called chondrocytes (produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans)

Environmental Factors Influencing Growth The primary environmental factors influencing growth are: The growth-inhibiting effects of malnutrition can be seen at any 1. Adequacy of nutrient time of development but are most supply and profound when they occur very early in life. Thus, maternal 2. Freedom from disease Lack of sufficient amounts of malnutrition may cause growth any of the essential amino retardation in the fetus, low birth acids, essential fatty acids, weight, infant mortality, low mental vitamins, or minerals growth, intellectual development interferes with growth. and total body growth Total protein and sufficient nutrients to provide energy must also be adequate.

Hormonal Influences on Growth The hormones important to growth are: most human Growth hormone, insulinlike growth factors I and II, thyroid hormones, insulin, testosterone, and estrogens Peptide growth factors, including the insulin-like growth factors, most of which act as paracrine and autocrine agents to stimulate differentiation and/or cell division of certain cell types. Growth Hormone and Insulin-Like Growth Factors. Growth hormone, secreted by the anterior pituitary, has little or no effect on fetal growth; rather most important for postnatal growth. Growth hormone promotes bone lengthening by stimulating maturation and cell division of the chondrocytes in the epiphyseal plates, thereby continuously widening the plates and providing more cartilaginous material for bone formation. An excess of growth hormone during childhood produces giantism, whereas deficiency produces dwarfism.

There is another messenger—insulinlike growth factor II (IGF-II)—that is closely related to IGFI. IGF-II, the secretion of which is independent of growth hormone, is also a crucial mitogen (that stimulates cell Division) during the prenatal period. It continues to be secreted throughout life, but its postnatal function is not known. It should not be surprising that adequate amounts of insulin are necessary for normal growth since insulin is, in all respects, an anabolichormone. Its inhibitory effect on protein degradation is particularly important with regard to growth. The thyroid hormones (TH) —thyroxine (T 4) and triiodothyronine (T 3)—are essential for normal growth because they are required for both the synthesis of growth hormone and the growth-promoting effects of that hormone. Accordingly, infants and children with hypothyroidism (deficient thyroid function) manifest retarded growth due to slowed bone growth.

Ø Testosterone in the male and estrogen in the female begins in earnest between the ages of 8 -10 and progressively increases to reach a plateau over the next 5 to 10 years. Ø Sex hormones stimulate the secretion of growth hormone and IGF-I (insulin-like growth factor I) that stimulate cell division Ø Testosterone, but not estrogen, exerts a direct anabolic effect on protein synthesis in many nonreproductive organs and tissues of the body.

v Cortisol, the major hormone secreted by the adrenal cortex in response to stress, can have potent antigrowth effects under certain conditions. v When present in high concentration, it inhibits DNA synthesis and stimulates protein catabolism in many organs, and it inhibits bone growth. v It causes bone breakdown by inhibiting osteoblasts and stimulating osteoclasts v Inhibits the secretion of growth hormone v Stimulates protein catabolism