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Physiology 72
Adenosine Triphosphate Functions as Energy Currency in Metabolism
 Carbs, fats, and proteins can all be used by cells to synthesize large quantities of ATP, which can be used as
energy source for almost all other cellular functions
 7.3 Calories/mol of ATP under standard conditions (as much as 12 under physiological conditions)
 Some reactions that require ATP only use a little of available calories, and remainder lost as heat
 ATP produced from
o Combustion of carbs – mainly glucose, but smaller amounts from other sugars such as fructose; occurs
in cytoplasm through anaerobic process of glycolysis and in mitochondria through aerobic Krebs cycle
o Combustion of fatty acids in cell mitochondria by beta-oxidation
o Combustion of proteins, which requires hydrolysis of their component amino acids and degradation of
amino acids to intermediate compounds of citric acid cycle and then to acetyl-CoA and CO2
 Among most important intracellular processes that require ATP energy is formation of peptide linkages between
amino acids during synthesis of proteins; depending on which types of amino acids are linked require from 0.5-5
Calories eventually stores in each of peptide linkages; 4 phosphate bonds expended during cascade of reactions
required to form each peptide linkage, so far more calories used than stored in peptide linkages
o ATP energy used to synthesize glucose from lactic acid and in synthesis of fatty acids from acetyl-CoA
o ATP used for synthesis of cholesterol, phospholipids, hormones, and almost all other substances of body
o Urea excreted by kidneys requires ATP for formation from ammonia
 Muscle contraction will not occur without ATP; myosin acts as enzyme to cause breakdown of ATP to ADP, thus
releasing energy required to cause contraction; only small amount of ATP normally degraded in muscles when
muscle contraction not occurring
 Active transport of most electrolytes, glucose, amino acids, and acetoacetate can occur against electrochemical
gradient with ATP
 Glandular secretion requires ATP because energy required to concentrate substances as they are secreted;
energy also required to synthesize the organic compounds to be secreted
 Energy used during propagation of nerve impulse derived from potential energy stored as concentration
differences of ions across membranes
o High concentration of K+ and low concentration of Na+ inside fiber (reverse outside fiber)
o Energy needed to pass each AP along fiber membrane derived from energy storage (concentration
differences) with small amounts of K+ transferring out of cell and Na+ into cell during each AP
o Active transport systems energized by ATP transport ions back through membrane to former positions
Phosphocreatine Functions as Accessory Storage Depot for Energy and as ATP Buffer
 Phosphocreatine - contains high-energy phosphate bonds; 3-8x more abundant than ATP; high-energy bond
contains about 8.5 Calories/mol under standard conditions and as many as 13 under conditions in body
 Phosphocreatine cannot act as direct coupling agent for energy transfer between foods and functional cellular
systems, but can transfer energy interchangeably with ATP
 When extra ATP available in cell, much of energy used to synthesize phosphocreatine, building up energy store
o When ATP begins to be used up, energy in phosphocreatine transferred back to ATP and then to
functional systems of cells (phosphocreatine + ADP  creatine + ATP)
 Higher energy level of phosphate bond in phosphocreatine causes reaction between phosphocreatine and ADP
to proceed rapidly toward formation of new ATP every time even small amount of ATP expends energy
o Keeps concentration of ATP at almost constant high level as long as any phosphocreatine remains
Anaerobic Versus Aerobic Energy
 Carbs are only significant foods that can be used to provide energy without utilization of O2; energy release
occurs during glycolytic breakdown of glucose or glycogen to pyruvic acid (2 mol of ATP formed)
o When stored glycogen in cell split to pyruvic acid, each mol of glucose in glycogen gives rise to 3 mol ATP
because free glucose entering cell must be phosphorylated using 1 mol of ATP before it can begin to
split and glycogen doesn’t because it’s already in phosphorylated state
o Best source of energy under anaerobic conditions is stored glycogen of cells
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When person stops breathing, already small amount of oxygen stored in lungs and additional amount stored in
Hgb of blood; sufficient to keep metabolic processes functioning for about 2 minutes; continued life after this
point requires glycolysis (helps survive another minute or so) and pyruvic acid converted to lactic acid
 Skeletal muscles can expend more strength in short bursts of activity; energy can’t come from oxidative
processes because they are too slow to respond; extra energy comes from ATP already present in cells,
phosphocreatine in cells, and anaerobic energy released by glycolytic breakdown of glycogen to lactic acid
o ATP storage in muscle can only hold max muscle contraction for a second or so, and phosphocreatine
can last 3-8 seconds
o Release of energy by glycolysis can occur much more rapidly than oxidative release of energy
o Most extra energy required during strenuous activity that lasts more than 5-10 seconds and less than 12 minutes comes from anaerobic glycolysis
o After exercise over, oxidative metabolism used to reconvert 4/5 of lactic acid into glucose, and
remainder becomes pyruvic acid and is degraded and oxidized in citric acid cycle
o Reconversion to glucose occurs primarily in liver cells, and glucose transported in blood back to muscles,
where it is stored as glycogen
 After period of strenuous exercise, person continues to breathe hard and consume large amounts of oxygen for
few minutes after; additional oxygen is used to repay O2 debt
o Conver lactic acid that has accumulated back to glucose
o Convert AMP and ADP to ATP
o Convert creatine and phosphate to phosphocreatine
o Establish normal concentrations of O2 bound with Hgb and myoglobin
o Raise concentration of O2 in lungs to normal level
 Larger quantities of phosphocreatine present in cells than ATP, so most of cell’s stored energy is there
 Oxidative metabolism cannot deliver bursts of extreme energy to cells as rapidly as anaerobic processes can, but
at slower rates of usage, it can continue as long as energy stores (mainly fat) exist
Control of Energy Release in Cell
 Michaelis-Menten equation  rate of reaction = K1[enzyme][substrate]/K2 + [substrate]
 When substrate concentration high, rate of chemical reaction determined almost entirely by concentration of
enzyme; for example, when large quantities of glucose enter renal tubules in person with DM, further increases
in tubular glucose have little effect on glucose reabsorption because transport enzymes saturated
o When substrate concentration becomes low enough that only small portion of enzyme required in
reaction, rate of reaction becomes directly proportional to substrate concentration as well as enzyme
concentration (relationship seen in absorption of substances from intestinal tract and renal tubules
when concentrations low)
 Because chemical reactions occur in series, overall rate of complex series of chemical reactions determined
mainly by rate of reaction at slowest step (rate-limiting step)
 Under resting conditions, concentration of ADP in cells extremely slight, so chemical reactions that depend on
ADP as substrate are slow (oxidative metabolic pathways that release energy from food or other pathways that
release energy in body), so ADP is major rate-limiting factor for almost all energy metabolism of body
o When cells become active, regardless of type of activity, ATP converted to ADP, increasing concentration
of ADP in direct proportion to degree of activity of cell; that ADP automatically increases rates of all
reactions for metabolic release of energy from food
o Amount of energy released in cell controlled by degree of activity of cell
o In absence of cellular activity, release of energy stops because all ADP becomes ATP
Metabolic Rate
 Metabolism of body – all chemical reactions in all cells of body
 Metabolic rate – rate of heat liberation during chemical reactions
 On average, 35% of energy in foods becomes heat during ATP formation; more energy becomes heat as it is
transferred from ATP to functional systems of cells; under optimal conditions, no more than 27% of all energy
from food finally used by functional systems
o Even when 27% of energy reaches functional systems of cells, most of this eventually becomes heat
o
When proteins synthesized, large portions of ATP used to form peptide linkages, which store energy, but
there is continuous turnover of proteins (some being degraded while others formed), so when proteins
degraded, energy stored in peptide linkages released in form of heat into body
o Movement of muscles during contraction creates friction between tissues, which generates heat
o Blood distends arterial system and distention represents reservoir of PE; as blood flows through
peripheral vessels, friction of different layers of blood flowing over one another and friction of blood
against walls of vessels turn energy into heat
o Essentially all energy expended by body eventually converted to heat
 Because person ordinarily not performing any external work, whole-body metabolic rate can be determined by
measuring total quantity of heat liberated from body in given time; done through calorimeter
o Subject placed in air chamber well insulated so no heat can leak through walls of chamber, and heat
from subjects body warms air of chamber
o Air temperature in chamber maintained at constant level by forcing air through pipes in cool water bath
o Rate of heat gain by water bath, measured with accurate thermometer, is equal to rate at which heat
liberated from subject’s body
 More than 95% of energy expended in body derived from reactions of O2 with different foods, so whole-body
metabolic rate can be calculated with high degree of accuracy from rate of oxygen utilization
o When 1 L O2 metabolized with glucose, 5.01 Calories of energy released; with starches, 5.06 Calories
released; with fat, 4.70 Calories released; with protein, 4.60 Calories released
o For average diet, quantity of energy liberated per L O2 used in body averages 4.825 Calories (energy
equivalent of O2); can use this to calculate rate of heat liberation in body from quantity of O2 used in
given period of time
o If person metabolizes only carbs during period of metabolic rate determination, calculated quantity of
energy liberated based on average would be too little, and if person gains most energy from fat,
calculated value would be greater than average
Energy Metabolism – Factors that Influence Energy Output
 In average American diet, 45% of daily energy intake from carbs, 40% from fats, and 15% from proteins
 Energy output partitioned into performing essential metabolic functions (basal metabolic rate), performing
various physical activities, digesting, absorbing and processing food, and maintaining body temperature
 Average man who weighs 70 kg who lies in bed all day (no eating, nothing) would use 1659 Calories; process of
eating and digesting food increases amount of energy used by 200 or so Calories; if he sits in a chair all day
without exercising, total energy requirements reach 2000-2250 Calories
 Amount of energy used to perform daily physical activities is normally about 25% of total energy expenditure
 Basal metabolic rate (BMR) – minimum level of energy required to exist; accounts for 50-70% of daily energy
expenditure in most sedentary individuals
o Because level of activity variable, BMR useful to compare one person’s metabolic rate with another
o Usual method for determining BMR is to measure rate of oxygen utilization over given period of time
under following conditions
 Person has not eaten food for at least 12 hours
 BMR determined after night of restful sleep
 No strenuous activity at least 1 hour before test
 All psychic and physical factors that cause excitement must be eliminated
 Temperature of air must be comfortable (68o-80o F)
 No physical activity permitted during test
o BMR normally averages 65-70 Calories per hour in average 70 kg man
o Much of BMR accounted for by essential activities of CNS, heart, kidneys, and other organs, but
variations in BMR among different individuals mainly related to differences in amount of skeletal muscle
and body size
o Skeletal muscle, even under resting conditions, accounts for 20-30% of BMR, so BMR usually corrected
for differences in body size by expressing it as Calories/hr/m2 body SA (calculated from height and
weight) – females BMR usually lower than men’s
o Much of decline in BMR with increasing age related to loss of muscle mass and replacement of muscle
with adipose tissue, which has lower rate of metabolism
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When thyroid gland secretes max amounts of thyroxine, metabolic rate rises 50-100% above normal; total loss
of thyroid secretion decreases metabolic rate 40-60%
o Thyroxine increases rates of chemical reactions of many cells in body; therefore increases metabolic rate
o Adaptation of thyroid (increased secretion in cold climates sand decreased secretion in hot climates)
contributes to differences in BMRs among people living in different geographical zones (people living in
arctic regions have BMRs 10-20% higher than those living in tropical regions
Testosterone can increase metabolic rate 10-15%; female sex hormones increase BMR by small amount, but not
enough to be significant
o Much of effect of testosterone related to anabolic effect to increase skeletal muscle mass
Growth hormone increases metabolic rate by stimulating cellular metabolism and increasing skeletal muscle
mass; in adults with GH deficiency, replacement with recombinant GH increases basal metabolic rate 20%
Fever, regardless of cause, increases chemical reactions of body by 120% for every 10o C rise in temperature
Metabolic rate decreases 10-15% below normal during sleep because of decreased tone of skeletal musculature
and decreased activity of CNS
Prolonged malnutrition can decrease metabolic rate 20-30% due to paucity of food substances in cells; in final
stages of many diseases, inanition that accompanies disease causes marked decrease in metabolic rate to extent
that body temp may fall several degrees shortly before death
Factor that most dramatically increases metabolic rate is strenuous exercise; short bursts of max muscle
contraction in single muscle can liberate as much as 100x normal resting amount of heat for few seconds
o For entire body, max muscle exercise can increase overall heat production of body for a few seconds to
50x normal, or about 20x normal for more sustained exercise in well-trained athlete
Even in sedentary individuals who perform little or no daily exercise or physical work, significant energy spent on
spontaneous physical activity required to maintain muscle tone and body posture or on nonexercise activities
such as fidgeting (nonexercise activities account for 7% of person’s daily energy usage)
After meal ingested, metabolic rate increases as result of different chemical reactions associated with digestion,
absorption, and storage of food in body (thermogenic effect of food)
o After meal that contains large quantity of carbs or fats, metabolic rate usually increases about 4%; after
high-protein meal, metabolic rate begins rising within an hour, reaching a max of 30% above normal,
lasting 3-12 hours (specific dynamic action of protein)
o Thermogenic effect of food accounts for 8% of total daily energy expenditure in many persons
Shivering provides regulated means of producing heat by increasing muscle activity in response to cold stress
Nonshivering thermogenesis – stimulated by SNS activation, which releases epinephrine and norepinephrine,
which increases metabolic activity and heat generation
o Brown fat – SNS stimulation causes liberation of large amounts of heat; has large numbers of
mitochondria and many small globules of fat instead of one large fat globule; in these cells, process of
oxidative phosphorylation in mitochondria mainly uncoupled (when cells stimulated by SNS,
mitochondria produce large amount of heat, but almost no ATP, so almost all released oxidative energy
immediately becomes heat)
 Neonate has considerable number of brown fat cells, and max SNS stimulation can increase
metabolism by more than 100%
 Magnitude in adults, who have virtually no brown fat, probably less than 15%, but might
increase significantly after cold adaptation
o Nonshivering thermogenesis may serve as buffer against obesity; SNS activity increased in obese
patients who have persistent excess caloric intake; possibly mediated through effects of increased
leptin, which activates pro-opiomelanocortin neurons in hypothalamus; SNS stimulation, by increasing
thermogenesis, helps limit excess weight gain