Chapter 24 -Nutrition, Metabolism, and Body Temperature Regulation

Nutrition

• Nutrient - substance that promotes normal growth, maintenance and repair
• Major nutrients - carbohydrates, lipids, and proteins
• Other nutrients - vitamins and minerals (and technically speaking, water)

• Carbohydrates
  • Complex carbohydrates (starches) are found in bread, cereal, flour, pasta, nuts, and potatoes
  • Simple carbohydrates (sugars) are found in soft drinks, candy, fruit, and ice cream
  • Glucose is the molecule ultimately used by body cells to make ATP
  • Neurons and RBCs rely almost entirely upon glucose to supply their energy needs
  • Excess glucose is converted to glycogen or fat and stored
  • The minimum amount of carbohydrates needed to maintain adequate blood glucose levels is 100 grams per day
  • Starchy foods and milk have nutrients such as vitamins and minerals in addition to complex carbohydrates
  • Refined carbohydrate foods (candy and soft drinks) provide energy sources only and are referred to as "empty calories"
• Lipids
  • The most abundant dietary lipids, triglycerides, are found in both animal and plant foods
  • Essential fatty acids - linoleic and linolenic acid, found in most vegetables, must be ingested
  • Dietary fats:
    • Help the body to absorb vitamins
    • Are a major energy fuel of hepatocytes and skeletal muscle
    • Are a component of myelin sheaths and all cell membranes
  • Fatty deposits in adipose tissue provide:
    • A protective cushion around body organs
    • An insulating layer beneath the skin
    • An easy-to-store concentrated source of energy
  • Dietary Requirements
    • Higher for infants and children than for adults
    • The American Heart Association suggests that:
      • Fats should represent less than 30% of one's total caloric intake
      • Saturated fats should be limited to 10% or less of one's total fat intake
      • Daily cholesterol intake should not exceed 200 mg
• Proteins
  • Complete proteins that meet all the body's amino acid needs are found in eggs, milk, milk products, meat, and fish
  • Incomplete proteins are found in legumes, nuts, seeds, grains, vegetables
  • Proteins supply:
    • Essential amino acids, building blocks for nonessential amino acids
    • Nitrogen for nonprotein nitrogen-containing substances
  • Daily intake should be approximately 0.8g/kg of body weight
  • All-or-none rule - All amino acids needed must be present at the same time for protein synthesis to occur
  • Adequacy of caloric intake - Protein will be used as fuel if there is insufficient carbohydrate or fat available
  • Nitrogen balance
    • The rate of protein synthesis equals the rate of breakdown and loss
    • Positive - synthesis exceeds breakdown (normal in children and tissue repair)
    • Negative - breakdown exceeds synthesis (e.g., stress, burns, infection, or injury)
  • Hormonal control - Anabolic hormones accelerate protein synthesis
• Vitamins
  • Organic compounds needed for growth and good health
  • They are crucial in helping the body use nutrients and often function as coenzymes
  • Only vitamins D, K, and B are synthesized in the body; all others must be ingested
  • Water-soluble vitamins (B-complex and C) are absorbed in the gastrointestinal tract
    • B12 additionally requires gastric intrinsic factor to be absorbed
  • Fat-soluble vitamins (A, D, E, and K) bind to ingested lipids and are absorbed with their digestion products
  • Vitamins A, C, and E also act in an antioxidant cascade
• Minerals
  • Seven minerals are required in moderate amounts
    • Calcium, phosphorus, potassium, sulfur, sodium, chloride, and magnesium
  • Dozens are required in trace amounts
  • Minerals work with nutrients to ensure proper body functioning
  • Calcium, phosphorus, and magnesium salts harden bone
  • Sodium and chloride help maintain normal osmolarity, water balance, and are essential in nerve and muscle function
  • Uptake and excretion must be balanced to prevent toxic overload

Metabolism

• Metabolism - all chemical reactions necessary to maintain life
• Cellular respiration - food fuels are broken down within cells and some of the energy is captured to produce ATP
  • Anabolic reactions - synthesis of larger molecules from smaller ones
  • Catabolic reactions - hydrolysis of complex structures into simpler ones
• Enzymes shift the high-energy phosphate groups of ATP to other molecules
  • These phosphorylated molecules are activated to perform cellular functions
• Stages of Metabolism
  • Energy-containing nutrients are processed in three major stages
    • Digestion - breakdown of food; nutrients are transported to tissues
    • Anabolism and formation of catabolic intermediates where nutrients are:
      • Built into lipids, proteins, and glycogen
      • Broken down by catabolic pathways to pyruvic acid and acetyl CoA
    • Oxidative breakdown - nutrients are catabolized to carbon dioxide, water, and ATP
• Mechanisms of ATP Synthesis:
  • Oxidation-Reduction (Redox) Reactions
    • Oxidation occurs via the gain of oxygen or the loss of hydrogen
    • Whenever one substance is oxidized, another substance is reduced
    • Oxidized substances lose energy
    • Reduced substances gain energy
    • Coenzymes act as hydrogen (or electron) acceptors
    • Two important coenzymes are nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD)
  • Substrate-Level Phosphorylation
    • High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP
    • ATP is synthesized via substrate-level phosphorylation in glycolysis and the Krebs cycle
  • Oxidative Phosphorylation
    • Uses the chemiosmotic process whereby the movement of substances across a membrane is coupled to chemical reactions
    • Is carried out by the electron transport proteins in the cristae of the mitochondria
      • Nutrient energy is used to pump hydrogen ions into the intermembrane space
      • A steep diffusion gradient across the membrane results
      • When hydrogen ions flow back across the membrane through ATP synthase, energy is captured and attaches phosphate groups to ADP (to make ATP)
• Carbohydrate Metabolism
  • Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism
  • Oxidation of glucose is shown by the overall reaction: C₆H₁₂O₆ + 6O₂ ----> 6H₂O + 6CO₂ + 36 ATP + heat
  • Glucose is catabolized in three pathways
    • Glycolysis ...(another animation (Anaerobic,,, another animation)
    • Aerobic
      • Krebs cycle (Prep Step - CoA)
      • The electron transport chain and oxidative phosphorylation (NADH and FADH₂)
• ATP Synthase
  • The electrochemical proton gradient across the inner membrane:
    • Creates a pH gradient
    • Generates a voltage gradient
  • These gradients cause H+ to flow back into the matrix via ATP synthase
    • The enzyme consists of three parts: a rotor, a knob, and a rod
    • Current created by H+ causes the rotor and rod to rotate
    • This rotation activates catalytic sites in the knob where ADP and Pi are combined to make ATP
• Glycogenesis, Glycogenolysis and Gluconeogenesis
  • Glycogenesis - formation of glycogen when glucose supplies exceed cellular need for ATP synthesis
  • Glycogenolysis - breakdown of glycogen in response to low blood glucose
  • Gluconeogenesis
    • The process of forming sugar from noncarbohydrate molecules
    • Takes place mainly in the liver
    • Protects the body, especially the brain, from the damaging effects of hypoglycemia by ensuring ATP synthesis can continue

Lipid Metabolism

• Most products of fat metabolism are transported in lymph as chylomicrons
• Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells
• Only neutral fats are oxidized for energy via two pathways
• Glycerol pathway
  • Glycerol is converted to glyceraldehyde phosphate
    • Glyceraldehyde is ultimately converted into acetyl CoA
    • Acetyl CoA enters Krebs cycle
• Fatty acids pathway
  • Fatty acids undergo beta oxidation which produces:
    • Two-carbon acetic acid fragments, which enter the Krebs cycle
    • Reduced coenzymes, which enter the electron transport chain
• Lipogenesis and Lipolysis
  • Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse
  • Oxaloacetic acid is necessary for the complete oxidation of fat
    • Without it, acetyl CoA is converted into ketones (ketogenesis)
  • Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides
  • Glucose is easily converted into fat since acetyl CoA is:
    • An intermediate in glucose catabolism
    • The starting molecule for the synthesis of fatty acids

Protein Metabolism

• Excess dietary protein results in amino acids being:
  • Oxidized for energy
  • Converted into fat for storage
• Amino acids must be deaminated prior to oxidation for energy
• Deaminated amino acids are converted into:
  • Pyruvic acid
  • One of the keto acid intermediates of the Krebs cycle
• These events occur as transamination, oxidative deamination, and keto acid modification
  • Transamination - switching of an amine group from an amino acid to a keto acid (usually a-ketoglutaric acid of the Krebs cycle)
    • Typically, glutamic acid is formed in this process
  • Oxidative deamination - the amine group of glutamic acid is:
    • Released as ammonia
    • Combined with carbon dioxide in the liver
    • Excreted as urea by the kidneys
  • Keto acid modification - keto acids from transamination are altered to produce metabolites that can enter the Krebs cycle

State of the Body

• The body exists in a dynamic catabolic-anabolic state
• Organic molecules (except DNA) are continuously broken down & rebuilt
• The body's total supply of nutrients constitutes its nutrient pool
• Amino acid pool -body's total supply of free amino acids is the source for:
  • Resynthesizing body proteins
  • Forming amino acid derivatives
  • Gluconeogenesis
• Interconversion Pathways of Nutrients
  • Carbohydrates are easily and frequently converted into fats
  • Their pools are linked by key intermediates
  • They differ from the amino acid pool in that:
    • Fats and carbohydrates are oxidized directly to produce energy
    • Excess carbohydrate and fat can be stored
• Absorptive and Postabsorptive States
  • Absorptive State
    • Metabolic controls equalize blood nutrient concentrations between two states
      • Absorptive -The time during and shortly after nutrient intake
        • 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
    • 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
      • In adipose tissue- glucose and fats are converted and stored as fat
      • All tissues use glucose to synthesize ATP
    • 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, CCK, and secretin
      • Insulin enhances:
        • Active transport of amino acids into tissue cells
        • Facilitated diffusion of glucose into tissue
      • 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
  • Postabsorptive State
    • The time when the GI tract is empty
    • Energy sources are supplied by the breakdown of body reserves
    • 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
    • Principle Pathways in the Postabsorptive State
      • In muscle:
        • Protein is broken down to amino acids
        • Glycogen is converted to ATP and pyruvic acid
      • In the liver:
        • Amino acids, pyruvic acid, glycogen, & 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
    • 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
      • 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
  • Hepatocytes carry out over 500 intricate metabolic functions
  • 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, degrades hormones, and detoxifies substances

Lipoproteins

• Lipoproteins classified
  • HDLs - high-density lipoproteins have more protein content
    • HDLs transport excess cholesterol from peripheral tissues to the liver
    • Also serve the needs of steroid-producing organs
    • High levels of HDL are thought to protect against heart attack component
  • LDLs - low-density lipoproteins have a considerable cholesterol
    • LDLs transport cholesterol to the peripheral tissues and regulate cholesterol synthesis
    • High levels of LDL increase the risk of heart attack
  • VLDLs - very low density lipoproteins are mostly triglycerides
    • The liver is the main source of VLDLs, which transport triglycerides to peripheral tissues (especially adipose)
• Cholesterol
  • Is the structural basis of bile salts, steroid hormones, and vitamin D
  • Makes up part of the hedgehog molecule that directs embryonic development
  • Is transported to and from tissues via lipoproteins
  • Plasma Cholesterol Levels
    • The liver produces cholesterol:
      • 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
    • 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
• 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
• 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
    • GLP-1 and serotonin make us feel full and satisfied
  • Feeding behavior and hunger depend on one or more of five factors
    • Neural signals from the digestive tract
    • Bloodborne signals related to the body energy stores
      • High plasma levels of nutrients that signal depressed eating
        • Plasma glucose levels
        • Amino acids in the plasma
        • Fatty acids and leptin
    • Hormones, body 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
• Control of Feeding Behavior and Satiety
  • Leptin, secreted by fat tissue, appears to be the overall satiety signal
    • Acts on the ventromedial hypothalamus
    • Controls appetite and energy output
    • Suppresses the secretion of neuropeptide Y, a potent appetite stimulant
  • Blood levels of insulin and glucocorticoids play a role in regulating leptin release
• 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
  • Basal metabolic rate (BMR)
    • 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, 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 36.2C (98.2F); optimal enzyme activity occurs at this temperature
• Temperature spikes above this range denature proteins and depress neurons
• 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 (20C-40C)
• Role of the Hypothalamus
  • The main thermoregulation center is the preoptic region of the hypothalamus
  • The heat-loss and heat-promoting centers comprise the 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
• 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

Developmental Aspects

• Good nutrition is essential in utero as well as throughout life
• Lack of proteins needed for fetal growth and in the first three years of life can lead to mental deficits and learning disorders
• With the exception of insulin-dependent diabetes mellitus, children free of genetic disorders rarely exhibit metabolic problems
• In later years, non-insulin-dependent diabetes mellitus becomes a major problem
• Many agents prescribed for age-related medical problems influence nutrition
  • Diuretics can cause hypokalemia by promoting potassium loss
  • Antibiotics can interfere with food absorption
  • Mineral oil interferes with absorption of fat-soluble vitamins
  • Excessive alcohol consumption leads to malabsorption problems, certain vitamin and mineral deficiencies, deranged metabolism, and damage to the liver and pancreas

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