Transcript Metabolism

Chapter 26
Lecture Outline
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Nutrition & Metabolism
• Nutrients
– Six classes are required
• carbohydrates - 125-175 g
• proteins - 50 g
• lipids - 80 - 100 g
• vitamins
• electrolytes / minerals
• Water Importance of water
4calories/gram
4calories/gram
9calories/gram
– solvent chemical reactions & body temp.
• metabolism
– BMR : amount of energy in kilocalories ; weight in
kilograms x 1 male x .9 female
– anabolism : make larger molecule, amino acids -->
proteins
– catabolism : break down digestion (hydrolysis)
• carbohydrate metabolism
– carbohydrate --> monosaccharide
– starches enzyme amylase
– Disaccharides sucrose, lactose and maltose
• Enzymes : sucrase, lactase, and maltase
– phases of cellular respiration
• lipid metabolism
– lipids --> fatty acids
enzyme: lipase
• protein metabolism
– proteins --> amino acids
enzymes: proteases
pepsin, trypsins
• General metabolic functions
– glycogenesis : making of glycogen
– glycogenolysis : breaking down of glycogen to
glucose
– glucogenesis : fats or proteins made into
glucose
• cholesterol metabolism
– 15 % from diet & 85 % made by liver
• LDL’s - low density lipoproteins transport
cholesterol to body cells
• HDL’s - high density lipoproteins transport
cholesterol to liver and out of body.
Body Energy Balance
• regulation of food intake
• nutrient levels
• hormones, body temp.
• glucose in blood & psychological
• body temperature regulation
• heat promoting
– vasoconstricting
» shivering, pyrogens
• heat loss
– radiation --> blood vessels skin dilating
– evaporation --> sweat
Metabolism – all chemical reactions in the
body
A. Energy conservation – food energy 
ATP
• Anaerobic – without O2,
glycolysis, fermentation
• Aerobic – with O2,
Kreb’s, electron transport
Glycolysis – anaerobic
Glycogen – (stored glucose)  ATP
lactic acid- formed with no or little O2
• Glycogen stored in muscles and liver
Glycogen + (2ATP)  (4ATP) + pyruvic
acid(citric acid) -formed from
breakdown
of glycogen under normal conditions
• Net gain of 2 ATP (s)
Krebs Cycle
A. Citric acid cycle (gain 2 ATP)
• By products of glycolysis citric or pyruvic
acid  ATP
• Net gain of 1 ATP per cycle 2 cycles
Electron Transport – aerobic
• Glucose  net gain of 32 ATP’s
Cellular Respiration – net gain of 36 ATP’s
• C6H12O6 + O2 + 2ATP + 38 ADP +
38( – P)  CO2 + H2O + 38 ATP
Fermentation – anaerobic “yeasts” and
bacteria
A. Alcohol – sugar or starch  alcohol +
carbon dioxide
B. Lactate – lactose  lactic acid + CO2
Pyruvic acid is turned into lactic acid
Energy sources in the human
“Cellular Respiration” total of 36 ATP’s
• Glycolysis – 2 ATP’s anaerobic
• Krebs – 2 ATP’s aerobic
• Electron transport – 32 ATP’s aerobic
Nutrition and Metabolism
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Nutrition
Carbohydrate Metabolism
Lipid and Protein Metabolism
Metabolic States and Metabolic Rate
Body Heat and Thermoregulation
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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
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Gut-Brain Peptides
• Appetite regulators
– short term
• effects last minutes to hours
– long term
• effects last weeks to years
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Short-term Appetite Regulators
• Ghrelin – produces hunger
– from parietal cells of empty stomach
– also stimulates hypothalamus release of
human growth hormone releasing hormone
• Peptide YY – satiety
– secreted in proportion to calories consumed
– acts as ileal break
• slows stomach emptying
• Cholecystokinin – satiety
– from enteroendocrine cells of duodenum and jejunum
– appetite-suppressing effect on brain
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Long-term Appetite Regulators
• Leptin – secreted by adipocytes in proportion
to body fat stores
• Insulin – pancreatic beta cells
– effect similar to leptin (but weaker)
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Appetite Regulation
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Serum Lipoproteins
• Categorized into 4 groups by density: more
protein = higher density
– chylomicrons
– very low-density (VLDLs)
– low-density (LDLs)
– high-density (HDLs)
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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
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HDL
• Production and function
– liver produces an empty protein shell
– travels through blood, picks up cholesterol
– delivers cholesterol to liver, for elimination in bile
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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
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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
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Lipoprotein Processing
• Three pathways
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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
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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
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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
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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
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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
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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
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Carbohydrate Metabolism
• Dietary carbohydrate burned as fuel within
hours of absorption (glucose catabolism)
C6H12O6 + 6O2  6CO2 + 6H2O
• Transfers energy from sugar to ATP
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Glucose Catabolism
• Series of small steps to efficiently transfer energy
to ATP (reduces energy lost as heat)
• Three major pathways
– Anaerobic
glycolysis (yields 2 ATP)
– aerobic respiration (yields 34-36 ATP)
Krebs cycle(2ATP) and electron transport(32 ATP)
– anaerobic fermentation (if no O2 available)
• pyruvic acid reduced to lactic acid
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Overview of ATP Production
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Anaerobic Fermentation
• Fate of pyruvic acid depends on oxygen availability
• In an exercising muscle, demand for ATP > oxygen supply;
ATP produced by glycolysis
+
• 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
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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
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Overview of ATP Production
• Complete aerobic oxidation of glucose to CO2
and H2O produces 36-38 ATP
– efficiency rating of 40% -- rest is body heat
– ADP bonds with recharged Phosphates to make
ATP
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ATP Generated by Oxidation of Glucose
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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
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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)
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Lipogenesis and Lipolysis Pathways
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Ketogenesis
• Fatty acids catabolized into acetyl groups (by betaoxidation in mitochondrial matrix) may
– enter citric acid cycle as acetyl-CoA
– undergo ketogenesis
• metabolized by liver to produce ketone bodies
• rapid or incomplete oxidization of fats raises blood ketone
levels (ketosis) and may lead to a pH imbalance (ketoacidosis)
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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)
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Urea Synthesis
• Liver converts
ammonia (NH3) to
urea which is
removed from blood
by kidneys
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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
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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
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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 from loss of
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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
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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
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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
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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
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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.
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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
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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
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Thermoregulation
• Hypothalamic thermostat monitors
temperature of blood and skin, signals
– heat-losing center to stimulate
• cutaneous vasodilation
• sweating
– signals heat-promoting center to stimulate
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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
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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 temperature  75 °F)
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