Chapter 26
Lecture
Outline
See PowerPoint Image Slides
for all figures and tables pre-inserted into
PowerPoint without notes.
26-1
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Nutrition and Metabolism
•
•
•
•
•
Nutrition
Carbohydrate Metabolism
Lipid and Protein Metabolism
Metabolic States and Metabolic Rate
Body Heat and Thermoregulation
26-2
Body Weight
• Stable with equal energy intake and output
– around a homeostatic set point
• Determined by combination of
environmental and hereditary factors
– 30-50% of variation between individuals due to
heredity
– rest due to eating and exercise habits
26-3
Gut-Brain Peptides
• Appetite regulators
– short term
• effects last minutes to hours
– long term
• effects last weeks to years
26-4
Short-term Appetite Regulators
• Ghrelin – produces hunger
• Peptide YY – satiety
• Cholecystokinin – satiety
26-5
Short-term Appetite Regulators
• Ghrelin – hunger
– from parietal cells of empty stomach
– also stimulates hypothalamus release of
human growth hormone releasing hormone
26-6
Short-term Appetite Regulators
• Peptide YY (PPY) – satiety
– from enteroendocrine cells in ileum and colon
– secreted in proportion to calories consumed
– acts as ileal break
• slows stomach emptying
26-7
Short-term Appetite Regulators
• Cholecystokinin (CCK) – satiety
– from enteroendocrine cells of duodenum and
jejunum
– appetite-suppressing effect on brain
26-8
Long-term Appetite Regulators
• Leptin – secreted by adipocytes in
proportion to body fat stores
• Insulin – pancreatic beta cells
– effect similar to leptin (but weaker)
26-9
Hypothalamus
•
Receptors for gut-brain peptides that
regulate release of:
1. neuropeptide Y (hunger)
• stimulated by gherlin
• inhibited by PYY, leptin, and insulin
2. melanocortin (satiety)
• stimulated by leptin, and CCK
26-10
Appetite Regulation
26-11
Other Factors in Appetite Regulation
• Appetite is briefly satisfied by
– chewing
– swallowing
– stomach filling
• Neurotransmitters stimulate desire for
different foods
– norepinephrine – carbohydrates
– galanin – fats
– endorphins – protein
26-12
Calories
• One calorie - amount of heat required to
raise temperature of 1 g of water 1 °C
– 1000 calories is a kilocalorie or Calorie
• Fats contain about 9 kcal/g
• Carbohydrates and proteins, about 4 kcal/g
– sugar and alcohol are “empty” calories -- few
nutrients
• Substance used for fuel is oxidized
primarily to make ATP
26-13
Nutrients
• Ingested chemical used for growth, repair
or maintenance
• Macronutrients consumed in large amounts
– proteins, fats and carbohydrates
• Micronutrients needed in small amounts
• Recommended daily allowances (RDA)
– safe estimate of daily intake for standard needs
• Essential nutrients can not be synthesized
– minerals, vitamins, 8 amino acids and 1-3 fatty
acids must be consumed in the diet
26-14
Carbohydrates
• Carbohydrates found in 3 places in body
– muscle and liver glycogen; blood glucose
• Most carbohydrate serves as fuel
– neurons and RBCs depend on glucose
• Sugars do serve as structural components
– nucleic acids, glycoproteins and glycolipids,
ATP
• Blood glucose carefully regulated by
insulin and glucagon
26-15
RDA and Dietary Sources of Carbs
• Carbohydrates are rapidly oxidized, RDA greater
than any other nutrient (175 g/day)
• Dietary sources:
– monosaccharides = glucose, galactose and fructose
• liver converts galactose and fructose to glucose
– outside hepatic portal system, only blood sugar is glucose
– normal blood sugar concentration ranges 70 to 110 mg/dL
– disaccharides = table sugar (sucrose), maltose,
lactose
– polysaccharides = starch, glycogen and cellulose
• Nearly all dietary carbohydrates come from
plants
26-16
Dietary Fiber
• Fibrous material that resists digestion
• Fiber is important to diet (RDA is 30 g/day)
– excess interferes with mineral absorption - iron
• Water-soluble fiber (pectin)
–  blood cholesterol and LDL levels
• Water-insoluble fiber (cellulose, lignin)
– absorbs water in intestines, softens stool,
gives it bulk, speeds transit time
26-17
Lipids
• Average adult male 15% fat; female 25% fat
– body’s stored energy
• hydrophobic, contains 2X energy/g, compact
storage
• glucose and protein sparing (no protein utilized for
energy)
– fat-soluble vitamins (A,D,E,K) absorbed with
dietary fat
• ingest less than 20 g/day risks deficiency
26-18
Functions of Lipids
• Diverse functions
– structural
• phospholipids and cholesterol are components of
plasma membranes and myelin
– chemical precursors
• cholesterol - a precursor of steroids, bile salts and
vitamin D
• fatty acids - precursors of prostaglandins and other
eicosanoids
26-19
Fat Requirements and Sources
• Should be less than 30% of daily calorie intake
– typical American gets 40-50%
• Most fatty acids synthesized by body
– essential fatty acids must be consumed
• Saturated fats
– animal origin -- meat, egg yolks and dairy products
• Unsaturated fats
– found in nuts, seeds and most vegetable oils
• Cholesterol
– found in egg yolks, cream, shellfish, organ meats and
other meats
26-20
Serum Lipoproteins
• Lipids transported in blood as lipoproteins
– protein and phospholipid coat around a
hydrophobic cholesterol and triglyceride core
– soluble in plasma; bind to cells for absorption
26-21
Serum Lipoproteins
• Categorized into 4 groups by density:
more protein = higher density
– chylomicrons
– very low-density (VLDLs)
– low-density (LDLs)
– high-density (HDLs)
26-22
Serum Lipoproteins
26-23
Chylomicrons
• Form in absorptive cells of small intestine
– enter lymphatic system, then blood
– capillary endothelium has lipoprotein lipase
to hydrolyze monoglycerides
– resulting free fatty acids (FFAs) and glycerol
enter fat cells to be resynthesized into
triglycerides for storage
– chylomicron remnant degraded by liver
26-24
VLDL and LDL
• VLDL
– produced by liver to transport lipids to
adipose tissue for storage
– when triglycerides removed become LDLs
(mostly cholesterol)
• LDL
– absorbed by cells in need of cholesterol for
membrane repair or steroid synthesis
26-25
HDL
• Production and function
– liver produces an empty protein shell
– travels through blood, picks up cholesterol
– delivers cholesterol to liver, for elimination in
bile
26-26
Total Cholesterol
• Desirable to maintain total cholesterol
concentration of < 200 mg/dL
– most cholesterol is endogenous
– dietary restrictions lower blood cholesterol levels
• by 5% with restriction of dietary cholesterol
• by 15 to 20% with restriction of certain saturated fats
– vigorous exercise lowers blood cholesterol
26-27
Desirable Lipoprotein Levels
• High levels of HDL
– indicate cholesterol is being removed from arteries
• Low levels LDL
– high LDL correlates with cholesterol deposition in
arteries
• Recommendations
– exercise regularly
– avoid smoking, saturated fats, coffee and stress
26-28
Lipoprotein Processing
• Three pathways
26-29
Proteins
• 12-15% of body mass
– mostly in skeletal muscles
• Functions
– muscle contraction
• movement of body, cells, cell structures
– cell membranes (receptors, cell identity, pumps)
– fibrous proteins (collagen, keratin)
• structural
– globular proteins (antibodies, myoglobin, enzymes)
• functional
– plasma proteins: blood osmolarity and viscosity
26-30
Requirements for Protein
• RDA - 44-60 g/day
• Nutritional value depends on proportions
of amino acids
– 8 essential amino acids can not be
synthesized
• isoleucine, leucine, lysine, methionine,
phenylalanine, threonine, tryptophan and valine
• Cells do not store surplus protein
• Complete proteins (dietary)
– supply all amino acids in right amount needed
to synthesize protein
26-31
Dietary Sources
• Animal proteins (meat, eggs and dairy) are
complete proteins
– closely match human proteins in amino acid
composition
• Plant sources must be combined in the
right proportions
– beans and rice are a complementary choice
26-32
Nitrogen Balance
• Rate of nitrogen ingestion equals rate of
excretion
– proteins are chief dietary source of nitrogen
– excretion chiefly as nitrogenous wastes
• Positive nitrogen balance
– occurs in children; they ingest more than they excrete
– promoted by growth and sex hormones
• Negative nitrogen balance
– body proteins being broken down for fuel (muscle
atrophy)
– glucocorticoids promote protein catabolism in states
of stress
26-33
Functions of Minerals
• Calcium and phosphorus
– bones and teeth
• Phosphorus
– phospholipids, ATP, CP, buffers, nucleic acids
• Calcium, iron, magnesium and manganese
– cofactors for enzymes
• Iron - essential for hemoglobin and myoglobin
• Chlorine - component of stomach acid (HCl)
• Mineral salts
– electrolytes; govern function of nerve and muscle
cells; regulate distribution of body water
26-34
Dietary Sources of Minerals
• Vegetables, legumes, milk, eggs, fish and
shellfish
• Animal tissues contain large amounts of
salt
– carnivores rarely lack salt in their diets
– herbivores often supplement by ingesting soils
• Recommended sodium intake is 1.1 g/day
• Typical American diet contains 4.5 g/day
26-35
Vitamins
• Body synthesizes some vitamins from
precursors
– niacin, vitamin A and D
– vitamin K, pantothenic acid, biotin, folic acid
• produced by intestinal bacteria
• Water-soluble vitamins (C, B)
– absorbed with water in small intestine; not
stored
• Fat-soluble vitamins (A, D, E, K)
– absorbed with dietary lipids; stored
26-36
Vitamins
26-37
Carbohydrate Metabolism
• Dietary carbohydrate burned as fuel within
hours of absorption (glucose catabolism)
C6H12O6 + 6O2  6CO2 + 6H2O
• Transfers energy from sugar to ATP
26-38
Glucose Catabolism
• Series of small steps to efficiently transfer
energy to ATP (reduces energy lost as heat)
• Three major pathways
– glycolysis (yields 2 ATP)
• glucose (6C) split into 2 pyruvic acid molecules (3C)
– aerobic respiration (yields 34-36 ATP)
• completely oxidizes pyruvic acid to CO2 and H2O
– anaerobic fermentation (if no O2 available)
• pyruvic acid reduced to lactic acid
– replenishes NAD+ so glycolysis can continue
26-39
Overview of ATP Production
26-40
Coenzymes
• Capture energetic electrons from glucose
during its catabolism
– coenzymes reduced
• gains energy (electron)
• charge reduced (electrons have negative charge)
• NAD+ (nicotinamide adenine dinucleotide)
– derived from niacin (B vitamin)
– NAD+ + H- + H+  NADH + H+
• FAD (flavin adenine dinucleotide)
– derived from riboflavin
– FAD + H- + H+  FADH2
26-41
Steps of Glycolysis (1)
• Phosphorylation
– glucose enters cell has phosphate added - ATP
used
– maintains favorable concentration gradient,
prevents glucose from leaving cell
• Priming
– isomerization occurs
– phosphorylation further activates molecule ATP used
• Cleavage
– molecule split into 2 three-carbon molecules
26-42
Steps of Glycolysis (2)
• Oxidation
– removes H+ and H– NAD+ + H-  NADH
• Dephosphorylation
– transfers phosphate groups to ADP to form
ATP
– 4 ATP produced (2 ATP used) for a net gain of
2 ATP
– produces pyruvic acid
26-43
Anaerobic Fermentation
• Fate of pyruvic acid depends on oxygen
availability
• In an exercising muscle, demand for ATP >
oxygen supply; ATP produced by glycolysis
– glycolysis can not continue without supply of NAD+
– NADH reduces pyruvic acid to lactic acid, restoring
NAD+
• Lactic acid travels to liver to be oxidized back to
pyruvic when O2 is available (oxygen debt)
– then stored as glycogen or released as glucose
• Fermentation is inefficient, not favored by brain
or heart
26-44
Aerobic Respiration
• Most ATP generated in mitochondria,
require oxygen as final electron acceptor
• Principle steps
– matrix reactions occur in fluids of
mitochondria
– membrane reactions whose enzymes are
bound to the mitochondrial membrane
26-45
Mitochondrial Matrix Reactions
• Three steps prepare pyruvic acid to enter
citric acid cycle
– decarboxylation so that a 3-carbon becomes a
2-carbon compound
– convert that to an acetyl group (remove H)
– bind it to coenzyme A
• Known as formation of acetyl-coenzyme A
26-46
Mitochondrial Matrix Reactions
26-47
Mitochondrial Matrix Reactions
• Citric Acid Cycle
• Acetyl-Co A (a C2 compound) combines with a
C4 to form a C6 compound (citric acid)-- start of
cycle
• Water is removed -- NAD+ is reduced to NADH -CO2 is removed to form a C5 compound-- NAD+
is reduced to NADH -- CO2 is removed to form a
C4 compound
• FAD is reduced to FADH2 -- water is added -NAD+ is reduced to NADH
• Original C4 compound is reformed – ready to
restart cycle
26-48
Summary of Matrix Reactions
2 pyruvate + 6H2O  6CO2
2 ADP + 2 Pi  2 ATP
8 NAD+ + 8 H- + 8 H+  8 NADH + 8 H+
(2 NADH produced during formation of acetyl-CoA)
2 FAD + 2 H2  2 FADH2
• Carbon atoms of glucose have all been carried
away as CO2 and exhaled.
• Energy lost as heat, stored in 2 ATP, 8 reduced
NADH, 2 FADH2 molecules of the matrix reactions
and 2 NADH from glycolysis
• Citric acid cycle is a source of substances for
synthesis of fats and nonessential amino acids 26-49
Membrane Reactions
• Purpose - to oxidize NADH and FADH2, transfer
their energy to ATP and regenerate them
• Reactions carried out by series of compounds
attached to inner mitochondrial membrane
called electron transport chain
– FMN is derivative of riboflavin, iron-sulfur centers,
Coenzyme Q, Copper ions bound to membrane
proteins and cytochromes (5 enzymes with iron
cofactors)
• As electrons are transferred along transport
chain, their potential orbital energy is released
• Final electron acceptor is oxygen: accepts 2
electrons and 2 H+ to form a water molecule
26-50
Electron Transport Chain
26-51
Chemiosmotic Mechanism
• Electron transport chain energy fuels
enzyme complexes
– pump protons from matrix into space between
inner and outer mitochondrial membranes
– creates steep electrochemical gradient for H+
across inner mitochondrial membrane
• Inner membrane is permeable to H+ at
channel proteins called ATP synthase
• Chemiosmotic mechanism - H+ flow
rushing back through these channels
drives ATP synthesis
26-52
Chemiosmotic ATP Synthesis
26-53
Overview of ATP Production
• NADH releases an electron pair to electron
transport system and H+ to prime pumps
– enough energy to synthesize 3 ATP
• FADH2 releases its electron pairs further
along electron-transport system
– enough energy to synthesize 2 ATP
• Complete aerobic oxidation of glucose to
CO2 and H2O produces 36-38 ATP
– efficiency rating of 40% -- rest is body heat
26-54
ATP Generated by Oxidation of Glucose
26-55
Glycogen Metabolism
• ATP is quickly used after it is formed -- it is not a
storage molecule
– extra glucose will not be oxidized, it will be stored
• Glycogenesis -- synthesis of glycogen
– stimulated by insulin (average adult contains 450 g)
• Glycogenolysis -- glycogen  glucose
– stimulated by glucagon and epinephrine
– only liver cells can release glucose back into blood
• Gluconeogenesis -- synthesis of glucose from
noncarbohydrates, such as fats and amino
acids
26-56
Glucose Storage and Use
26-57
Lipids
• Triglycerides are stored in adipocytes
– constant turnover of molecules every 3 weeks
• released into blood, transported and either oxidized or
redeposited in other fat cells
• Lipogenesis = synthesizing fat from other
sources
– amino acids and sugars used to make fatty acids and
glycerol
• Lipolysis = breaking down fat for fuel
– glycerol is converted to PGAL and enters glycolysis
– fatty acids are broken down 2 carbons at a time to
produce acetyl-CoA (beta oxidation)
26-58
Lipogenesis and Lipolysis Pathways
26-59
Ketogenesis
• Fatty acids catabolized into acetyl groups
(by beta-oxidation in mitochondrial matrix) may
– enter citric acid cycle as acetyl-CoA
– undergo ketogenesis
• metabolized by liver to produce ketone bodies
– acetoacetic acid
– -hydroxybutyric acid
– acetone
• rapid or incomplete oxidization of fats raises blood
ketone levels (ketosis) and may lead to a pH
imbalance (ketoacidosis)
26-60
Proteins
• Amino acid pool - dietary amino acids plus 100 g
of tissue protein broken down each day into free
amino acids
• May be used to synthesize new proteins
• As fuel -- first must be deaminated (removal of
NH2)--what remains is converted to pyruvic acid,
acetyl-CoA or part of citric acid cycle
– during shortage of amino acids, the reverse occurs for
protein synthesis
– the NH2 become ammonia (NH3) which is toxic and
which the liver converts to urea (excreted in urine)
26-61
Pathways of Amino Acid Metabolism
26-62
Urea Synthesis
• Liver converts
ammonia (NH3) to
urea which is
removed from
blood by kidneys
26-63
Absorptive State
• Lasts about 4 hours during and after a meal
– time of nutrient absorption and use for energy needs
• Carbohydrates
– blood glucose is available to all cells for ATP synthesis
– excess is converted by liver to glycogen or fat
• Fats
– taken up by fat cells from chylomicrons in the blood
– primary energy substrate for liver, fat and muscle cells
• Amino acids
– most pass through the liver and go onto other cells
– in liver cells, may be used for protein synthesis, used
for fuel for ATP synthesis or used for fatty acid
synthesis
26-64
Regulation of Absorptive State
• Regulated by insulin secreted in response to
elevated blood glucose and amino acid levels
and the hormones gastrin, secretin and
cholecystokinin
• Insulin
– increases the cellular uptake of glucose by 20-fold
– stimulates glucose oxidation, glycogenesis and
lipogenesis but inhibits gluconeogenesis
– stimulates active transport of amino acids into cells
and promotes protein synthesis
• high protein, low carbohydrate meals stimulate release of
both insulin and glucagon preventing hypoglycemia
26-65
Postabsorptive State
• Homeostasis of blood glucose critical to brain
– when stomach and small intestine are empty- stored
fuels are used
• Carbohydrates
– glucose is drawn from glycogen reserves for up to 4
hours and then synthesized from other compounds
• Fat
– adipocytes and liver cells convert glycerol to glucose
– free fatty acids are oxidized by liver to ketone bodies
• other cells use for energy-- leaving glucose for brain
• Protein metabolism
– used as fuel when glycogen and fat reserves depleted
– wasting away occurs with cancer and other diseases
26-66
from loss of appetite and altered metabolism
Regulation of Postabsorptive State
• By sympathetic nervous system and
glucagon
• Blood glucose drops, glucagon secreted
– glycogenolysis and gluconeogenesis raise
glucose levels
– lipolysis raises free fatty acid levels
26-67
Regulation of Postabsorptive State
• Sympathoadrenal effects
– promotes glycogenolysis and lipolysis under
conditions of injury, fear, anger and stress
– adipose, liver cells and muscle cells are richly
innervated and also respond to epinephrine
from adrenal medulla
– Cortisol from adrenal cortex promotes  blood
glucose
• fat and protein catabolism and gluconeogenesis
– Growth hormone – opposes rapid  in blood
glucose
26-68
Metabolic Rate
• Amount of energy used in the body in a given
period of time (kcal/hr or kcal/day)
– measured directly in calorimeter (water bath)
– measured indirectly by oxygen consumption
• Basal metabolic rate (BMR)
– relaxed, awake, fasting, room comfortable
temperature
– adult male BMR is 2000 kcal/day(slightly less female)
• Factors affecting total MR
– pregnancy, anxiety, fever, eating, thyroid hormones,
and depression
26-69
Body Heat and Thermoregulation
• Homeostasis requires heat loss to match
heat gain
• Hypothermia - excessively low body
temperature
– can slow metabolic activity and cause death
• Hyperthermia - excessively high body
temperature
– can disrupt enzymatic activity and metabolic
activity and cause death
• Thermoregulation - ability to balance heat
production and heat loss
26-70
Body Temperature
• “Normal” body temperature varies about 1.8
degrees F. in a 24-hour cycle
– low in morning and high in late afternoon
• Core body temperature is temperature of organs
in cranial, thoracic and abdominal cavities
– rectal temperature is an estimate
– adult varies normally from 99.0 - 99.7 degrees F.
• Shell temperature is temperature closer to the
surface (oral cavity and skin)
– adult varies normally from 97.9 - 98.6 degrees F.
26-71
Heat Production
• Comes from energy-releasing chemical
reactions such as nutrient oxidation and
ATP use
• From brain, heart, liver, endocrine and
muscles
– exercise greatly  heat production in muscle
26-72
Modes of Heat Loss
• Radiation - loss of body heat to objects around
us
– caused by molecular motion producing infrared
radiation
• Conduction - loss of body heat to the air which
when warmed rises to be replaced by cooler air
• Evaporation - heat loss as sweat evaporates
– extreme conditions as much as 2L of sweat lost per
hour, dissipating heat by as much as 600 kcal/hour
26-73
Thermoregulation
• Hypothalamic thermostat monitors
temperature of blood and skin,
signals
– heat-losing center to stimulate
• cutaneous vasodilation
• sweating
– signals heat-promoting center to
stimulate
•
•
•
•
cutaneous vasoconstriction
arrector pili muscle contraction
shivering thermogenesis (if needed)
nonshivering thermogenesis -  thyroid
hormone and BMR (seasonal adjustment)
• Behavioral thermoregulation
– get out of sun, remove heavy clothing 26-74
Disturbances of Thermoregulation
• Fever
– normal protective mechanism that elevates BMR
which produces more heat elevating the BMR, etc.
• Hyperthermia - exposure to excessive heat
– heat cramps are muscle spasms due to electrolyte
imbalance from excessive sweating
– heat exhaustion -- severe electrolyte imbalance
producing fainting, dizziness, hypotension
– heat stroke -- body temperature > 104 °F, may cause
delirium, convulsions, coma, and death
• Hypothermia - exposure to excess cold
– as core body temperature , BMR  causing a further
body temperature decrease, etc. (fatal if body
26-75
temperature  75 °F)