Overview of Liver: Metabolism and Energetics Introduction
• Next we consider bodily metabolism, or the chemical processes that make it possible for the cells to remain viable
• In particular • A review of the principal chemical processes of the cell • An analysis of their physiologic implications, especially the manner in which they
Metabolism Role of Adenosine Triphosphate in Metabolism
• Adenosine triphosphate (ATP) is an essential link between energy-utilizing and energy-producing functions of the body • Energy derived from the oxidation of
carbohydrates, proteins, and fats is used to convert adenosine diphosphate (ADP) to ATP
• ATP then consumed for cellular functions, including
• Active transport of molecules across cell membranes
• Contraction of muscles and performance of mechanical work
• Various synthetic reactions • Conduction of nerve impulses • Cell division and growth
• ATP is a combination of adenine, ribose, and three phosphate radicals
Metabolism Role of Adenosine Triphosphate in Metabolism
• The amount of free energy in each high energy bond of ATP varies with the surrounding conditions • 7,300 calories under standard conditions • 12,000 calories under physiological conditions
• ATP is present everywhere in the cytoplasm and nucleoplasm of all cells
• Essentially all physiologic mechanisms that require energy obtain it directly from ATP, or another similar high-energy compound, guanosine triphosphate (GTP)
• As food in cells is gradually oxidized, the released energy is used to form new ATP
• Normally, 90% or more of all the carbohydrates utilized by the body are used for ATP formation
Carbohydrate Metabolism Central Role of Glucose in Carbohydrate Metabolism
• The final products of carbohydrate digestion are almost entirely glucose, fructose, and galactose • Glucose comprises about 80% of total • After absorption from the intestinal tract,
much of the fructose and almost all the galactose are rapidly converted into glucose in the liver
• Glucose thus becomes the final common pathway for the transport of almost all carbohydrates to the tissue cells
• In liver cells, interconversions occur between glucose, fructose, and galactose • When the liver releases monosaccharides
back into the blood, the final product is almost entirely glucose
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Carbohydrate Metabolism Transport of Glucose Through the Cell Membrane
• Before glucose can be used by the body's tissue cells, it must be transported through the tissue cell membrane into the cellular cytoplasm • Glucose cannot easily diffuse through the pores of the cell membrane as its
molecular weight (180 Da) is above the molecular weight cutoff (100 Da) • However, glucose is transported by a membrane bound protein through
facilitated diffusion • The transport of glucose in the gastrointestinal membrane or the epithelium of the
renal tubules occurs by an active sodium-glucose co-transport • Active transport of sodium provides energy for absorbing glucose against a
Carbohydrate Metabolism Insulin Increases Facilitated Diffusion of Glucose • The rate of glucose transport as well as some other monosaccharides is greatly
increased by insulin
• When large amounts of insulin are secreted by the pancreas, the rate of glucose transport into most cells increases to 10+ times
• Conversely, the amount of glucose that can diffuse into most cells in the absence of insulin, with the exception of liver and brain cells, is far too little to supply the amount of glucose normally required for energy metabolism
• Thus, the rate of carbohydrate utilization by most cells is controlled by the rate of insulin secretion from the pancreas
Carbohydrate Metabolism Phosphorylation of Glucose
• Immediately on entry into the cells, glucose combines with a phosphate radical to form glucose-6-phosphate
• Phosphorylation serves to capture the glucose in the cell, as phoshorylated glucose will not diffuse out of the cell
• Phosphorylation is promoted mainly by the enzyme glucokinase in the liver and by hexokinase in most other cells
• Phosphorylation of glucose is almost completely irreversible • In liver cells, renal tubular epithelial cells, and intestinal epithelial cells, glucose
Carbohydrate Metabolism Glycogenolysis • Glycogenolysis involves the breakdown of glycogen to re-form glucose
• Here, each succeeding glucose molecule on each branch of the glycogen polymer is split away by phosphorylation, catalyzed by phosphorylase, which itself must be activated
• Epinephrine and glucagon can activate phosphorylase and thereby cause rapid glycogenolysis • Epinephrine is released by the adrenal medullae when the sympathetic nervous
system is stimulated • Glucagon is secreted by the alpha cells of the pancreas when the blood glucose
Carbohydrate Metabolism Glycolysis and the Formation of Pyruvic Acid • Glycolysis occurs by 10 successive chemical reactions
• Each step is catalyzed by at least one specific protein enzyme • Only a small portion of the free energy in the glucose molecule is released at
most steps
• 4 moles of ATP were formed for each mole of fructose-1,6-diphosphate that is split into pyruvic acid
• 2 moles of ATP were required to phosphorylate the original glucose to form fructose-1,6-diphosphate
• A net gain of 2 moles of ATP were achieved with for each mole of glucose • Thus 24 kcal of energy were generated from the 56 kcal in the original glucose,
for an overall efficiency of 43% • Remaining 57% is lost as heat
Carbohydrate Metabolism Glycolysis and the Formation of Pyruvic Acid • The next stage in the degradation of glucose
is a two-step conversion of the two pyruvic acid molecules
• Here, two carbon dioxide molecules and four hydrogen atoms are released, while the remaining portions of the two pyruvic acid molecules combine with coenzyme A, a derivative of the vitamin pantothenic acid, to form two molecules of acetyl-CoA
• In this conversion, no ATP is formed, but up to six molecules of ATP are formed when the four released hydrogen atoms are later oxidized
• The next stage in the degradation of the glucose molecule is called the citric acid cycle • Tricarboxylic acid cycle • Krebs cycle
• This is a sequence of chemical reactions in which the acetyl portion of acetyl-CoA is degraded to carbon dioxide and hydrogen atoms • Occurs in the matrix of the mitochondrion • Released hydrogen atoms will subsequently be oxidized releasing tremendous
• Considering the citric acid cycle as a whole • 2 acetyl-CoA molecules and 6 molecules of water enter into the citric acid cycle • 4 carbon dioxide molecules, 16 hydrogen atoms, 2 molecules of coenzyme A,
and 2 molecules of ATP are formed
• 24 H atoms are released from each molecule of glucose • 4 during formation of acetyl-CoA (x2) and 16 in the citric acid cycle • 20 of the 24 hydrogen atoms immediately combine with nicotinamide adenine
dinucleotide (NAD+), a derivative of the vitamin niacin, to form NADH • Reaction requires a specific dehydrogenase and NAD+ • Free H and NADH go on to form ATP
• First, mitochondria ionize H from food, to form of H+ as well as NADH
• Electrons, that are removed from H to cause the hydrogen ionization, immediately enter an electron transport chain in the inner membrane of the mitochondrion • Electron acceptors can be reduced or oxidized
by accepting or giving electrons • Electron transport chain members include
flavoprotein, several iron sulfide proteins, ubiquinone, and cytochromes B, C1, C, A, and A3
• Each electron is shuttled from one of these acceptors to the next until it finally reaches cytochrome A3, which is called cytochrome oxidase because it is capable of giving up two electrons and thus reducing elemental oxygen to form ionic oxygen, which then combines with hydrogen ions to form water
• As the electrons pass through the electron transport chain, large amounts of energy are produced and used to pump hydrogen ions into the outer chamber between the inner and outer mitochondrial membranes producing • A high concentration of positively charged
hydrogen ions in this chamber • A strong negative electrical potential in the
inner matrix
• ATPase converts ADP into ATP, utilizing the energy derived from this hydrogen ion flow as well as a free ionic phosphate radical (Pi)
• ATP is transferred from the inside of the mitochondrion back to the cell cytoplasm by facilitated diffusion • ADP is continually transferred in the other
Carbohydrate Metabolism ATP Formation From Glucose • During glycolysis, 4 molecules of ATP are formed, and 2 are expended to cause the
initial phosphorylation of glucose - giving a net gain of 2 molecules of ATP • During each citric acid cycle, 2 molecules of ATP are formed, 1 from each pyruvic
acid molecules formed from glucose • During glucose breakdown, a total of 24 hydrogen atoms are released during
glycolysis and the citric acid cycle • 20 H atoms are oxidized in oxidative phosphorylation, with the release of 3 ATP
molecules per 2 atoms of hydrogen metabolized, giving 30 ATP molecules • 4 H atoms hydrogen atoms are released by their dehydrogenase in oxidative
phosphorylation; 2 ATP molecules are usually released for every 2 H atoms oxidized, thus giving 4 ATP molecules
• Thus a maximum of 38 ATP molecules formed for each molecule of glucose degraded to carbon dioxide and water • Thus, 456,000 calories of energy can be stored as ATP, whereas 686,000
calories are released from glucose, giving an overall maximum efficiency of 66%
Carbohydrate Metabolism Control of Energy Release from Stored Glycogen • Release of energy from glucose is controlled in accordance with the cells' need for
ATP
• The enzyme phosphofructokinase, which promotes the formation of fructose-1,6-diphosphate, is a key regulator • Inhibition of this enzyme, in response to excess cellular ATP, decreases or even
stops glycolysis • Increases in ADP and AMP greatly increases phosphofructokinase activity,
thereby increasing metabolism • The citrate ion, formed in the citric acid cycle, inhibits phosphofructokinase, thus
linking the citric acid cycle to glycolysis
• Finally, AMP-ADP-ATP provides its own regulation • If all ADP has been converted into ATP, additional ATP simply cannot be formed • Then, when ATP is used, the newly formed ADP and AMP turn on the energy
processes again, and ADP and AMP are almost instantly returned to the ATP state
Carbohydrate Metabolism Anaerobic Glycolysis • In low oxygen conditions, glycolysis can still occur because it does not require
oxygen, but oxidative phosphorylation cannot take place • This process is extremely wasteful of glucose, because only 24,000 calories of
energy are used to form ATP for each molecule of glucose
• The two end products of the glycolytic reactions are pyruvic acid and hydrogen atoms in the form NADH and H+
• The buildup of either or both of these would stop the glycolysis • However, these two end products react with each other to form lactic acid
• Thus, under anaerobic conditions, the major portion of the pyruvic acid is converted into lactic acid, which diffuses readily out of the cells into the extracellular fluids and even into the intracellular fluids of other less active cells • Thus glycolysis can proceed for several minutes, supplying the body with
considerable extra quantities of ATP, in the absence of oxygen
Carbohydrate Metabolism Anaerobic Glycolysis • Once oxygen is available again after anaerobic glycolysis, lactic acid is rapidly
reconverted to pyruvic acid and NADH plus H+
• These are immediately oxidized to form large quantities of ATP
• Thus, formed lactic acid is not lost from the body because, when oxygen is once again available, it can be either reconverted to glucose or used directly for energy • Reconversion occurs mainly in the liver
• Heart muscle is especially capable of converting lactic acid to pyruvic acid and then using the pyruvic acid for energy, allowing the heart extra energy during heavy exercise
Carbohydrate Metabolism Pentose Phosphate Pathway • A second mechanism for the breakdown and oxidation
of glucose is called the pentose phosphate pathway, accounting for up to 30% of glucose breakdown • As an alternate pathway, it provides a source of
energy when enzymatic abnormalities occur • Glucose releases one molecule of carbon dioxide and
four atoms of hydrogen, forming a five-carbon sugar, D-ribulose-5-phosphate
• D-ribulose-5-phosphate can become one of several other five-, four-, seven-, and three-carbon sugars, and finally reforming glucose • Only 5 molecules of glucose are resynthesized for
every 6 reacted • By repeating the cycle, glucose can eventually be
converted into carbon dioxide and hydrogen • The released hydrogen combines with
nicotinamide adenine dinucleotide phosphate (NADP+), forming NADPH which can be used for the synthesis of fats from carbohydrates
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Carbohydrate Metabolism Glucose Conversion to Glycogen or Fat
• When glucose is not immediately required for energy, the extra glucose that continually enters the cells is either stored as glycogen or converted into fat
• Glucose is preferentially stored as glycogen until the cells have stored an amount sufficient to supply the energy needs of the body for only 12 to 24 hours
• When the glycogen-storing cells, primarily liver and muscle cells, approach saturation with glycogen, the additional glucose is converted into fat in liver and is stored as fat in adipocytes
Carbohydrate Metabolism Gluconeogenesis • When the body's stores of carbohydrates decrease below normal, moderate
quantities of glucose can be formed from amino acids and the glycerol portion of fat - gluconeogenesis • Gluconeogenesis is especially important in preventing an excessive reduction in
the blood glucose concentration during fasting
• The liver plays a key role in maintaining blood glucose levels during fasting by converting its stored glycogen to glucose (glycogenolysis) and by synthesizing glucose, mainly from lactate and amino acids (gluconeogenesis)
• Diminished carbohydrates in the cells and decreased blood sugar are the basic stimuli that increase the rate of gluconeogenesis
Lipid Metabolism Introduction • Lipids include triglycerides, phospholipids, and
cholesterol • Triglycerides and phospholipids contain fatty acids,
or long hydrocarbon chains that may be saturated or unsaturated and contain a carboxylic acid group (-COOH)
• Cholesterol contains a sterol nucleus that is synthesized from fatty acids
• Typical triglycerides in the human body include • Stearic acid, CH3(CH2)16COOH • Oleic acid, CH3(CH2)7CH=CH(CH2)7COOH • Palmitic acid, CH3(CH2)14COOH
Lipid Metabolism Transport of Lipids in the Body Fluids • Almost all fats, broken down into monoglycerides and fatty acids, are absorbed from
the intestines and into the intestinal lymph
• In intestinal epithelial cells, triglycerides are reformed and dispersed as chylomicron droplets, with the protein apoprotein B decorating their surface • Chylomicrons contain 87% triglycerides, 9% phospholipids, 3% cholesterol, 1%
apoprotein B • After eating, chylomicrons constitute 1 - 2% of plasma volume
• The capillary endothelium of the liver and adipose tissue contain lipoprotein lipase, which hydrolyzes triglycerides within the chylomicrons and thus releasing fatty acids and glycerol • Constituents are absorbed by surrounding cells and resynthesized into
• Most lipoproteins are formed in the liver, with some formed in the intestinal epithelium, and act to transport lipids in the blood
• Four major classes of lipoproteins include • Very low density lipoproteins, which are high in triglyceride concentration • Intermediate density lipoproteins, which are low in triglyceride concentration • Low density lipoproteins, which contain almost no triglyceride concentration • High density lipoproteins, which are high in protein concentration
Lipid Metabolism Fat Deposits • Fat, contained primarily in adipose tissue and the liver, acts to store triglycerides
• Adipocytes, or fat cells, are essentially fibroblasts with 80 - 95 vol% triglycerides, stored as liquids within large vesicles • Lipases, which catalyze the deposition of triglycerides from chylomicrons,
lipoproteins, and adipocytes, continually function, turning over the triglyceride content of adipocytes every 2 to 3 weeks
• The liver acts to degrade fatty acids, synthesize triglycerides, and synthesize other lipids (phospholipids and cholesterol) • High triglyceride concentrations in the liver occur in early starvation and diabetes
• Here, triglycerides are being obtained from adipose tissue in order to boost energy
• Liver triglyceride concentration, alternatively, describes the rate of lipid consumption for energy
Lipid Metabolism Triglyceride Utilization • About 40% of calories consumed by Americans are fats, almost equal to the amount
of calories consumed as carbohydrates
• Upon ingestion, triglycerides are hydrolyzed into fatty acids and glycerol • Fatty acids are used by almost all cells as an energy source • Glycerol is converted into glycerol-3-phosphate and enters glycolysis
• Fatty acids are transported into the mitochondria and then undergo beta-oxidation to yield acetyl-CoA, which then enters the citric acid cycle • Four H atoms are also released per carbon in the fatty acid chain
Lipid Metabolism Triglyceride Utilization • The resulting acetyl-CoA is then converted in the liver into ketone bodies, particularly
acetoacetic acid, acetone, or β-hydroxybutyric acid • These compounds then diffuse freely out of the liver and into the blood, where
they are distributed throughout the body • When received in distal tissues, these compounds are re-converted back into
acetyl-CoA and enter the citric acid cycle
• During starvation, diabetes, and an extremely high fat diet, a condition termed ketosis occurs, where the concentration of ketone bodies becomes very high • Carbohydrate metabolism stops, either due to the lack of carbohydrates
(starvation or high fat diet) or due to inhibited glucose transport into the cells (diabetes)
• Energy must then come from fat metabolism, increasing ketone body blood concentration
• However, the scarcity of oxaloacetate limits this mechanism, further increasing ketone body concentration
Lipid Metabolism Synthesis of Triglycerides • Storage of carbohydrates first occurs in the form of glycogen, but once “filled”
carbohydrates are then stored as triglycerides • (1) carbohydrates are converted to acetyl-CoA by glycolysis, (2) acetyl-CoA is
converted to malonyl-CoA, (3) malonyl-CoA combines with acetyl-CoA and eventually forms a fatty acid in a manner similar to the reverse of beta-oxidation, and (4) fatty acids combine with glycerol to form a triglyceride
• Storage of carbohydrates as fat is highly efficient as fat storage capacity is much larger than glycogen storage, and energy storage in fat is much higher (x2.5) than in glycogen
ACP-SH
ADP P H+
NADP+
NADPH H+
CoASH
KSase
ACP-SH
ATP HCO3
- ACP-SH
CoASH
CO2 H2O NADP+
NADPH H+
β-Ketoacyl-ACP reductase
β-Hydroxyacyl- ACP dehydratase
2,3-trans-Enoyl- ACP reductase
SO
CH3
CoAS
OCH3
ACPS
OCH3
KSase
SO
CH3
CoAS
O
CoA
O-O
SO
ACP
O-O
SO
ACP
CH3O
SO
ACP
CH3HO
SO
ACP
CH3
SO
ACP
CH3
ACP = acyl carrier protein KSase = β-ketoacyl-ACP synthase
Lipid Metabolism Phospholipids • The major phospholipids include
lecithins, cephalins, and sphingomyelin
• Phospholipids are formed throughout the body, however 90% are formed in the liver
• Phospholipid formation follows fat metabolism, although some compounds such as choline and inositol are required
• Phospholipids acts as • Lipoproteins in blood • Thromboplastin, for blood clotting • Sphingomyelin, in melin insulation • Phosphate donors in phosphate
Lipid Metabolism Atherosclerosis • Atherosclerosis involves the formation of fatty
lesions, atheromatous plaques, in the interior of arterial walls
• After damage to the vascular endothelium lining arterial wall, monocytes and lipids (LDLs) accumulate
• Monocytes adhere, migrate through, differentiate into macrophages
• Macrophages aggregate, cause inflammation, eventually causing a reduction in lumenal cross section, decreasing blood flow at very low lumen diameters
• Concurrently, sclerosis (fibrosis) of the artery becomes great, creating a stiff and rigid vessel
• Results include stiff arteries, clot formation, and potential block arterial blood flow
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Protein Metabolism • Proteins are polymeric amino acids, where the amino acid
sequence determines the protein function • An amino acid is formed from
• A central alpha-carbon, with one lone hydrogen • An amino (NH2) group • A carboxyl (COOH) group • An R side chain group determines the type of amino acid
• The central carbon atom is asymmetric, allowing the formation of L and D isomers • Proteins consist exclusively of L-amino acids
• A physiological pH (7.4) both the amino group and carboxyl group are ionized (amino group is NH3
+ / carboxyl group is COO-)
• Proteins are formed from a condensation reaction between an amino group and a carboxyl group, releasing water
Protein Metabolism Transport and Storage • Upon food digestion, almost all proteins are digested and absorbed in the form of
amino acids - rarely are polypeptides or proteins absorbed into the blood
• The normal blood concentration of amino acids is between 35 and 65 mg/dl • Concentration rises only slightly after eating, due to
• Digestion and absorption occur over the course of hours • Amino acid uptake by tissues, especially the liver, is quick
• Amino acids are too large for diffusion through cell membranes, thus are taken up by facilitated transport or active diffusion
• In the kidneys, amino acids are actively reabsorbed by the proximal tubular epithelium
• Absorbed amino acids are quickly reused in protein synthesis, thus storage of amino acids is low • Cells do contain small quantities of amino acids, releasable during deficiency • The liver contains proteins that are easily broken down for use as a amino acids • Excess amino acids can be converted into energy, fat, or glycogen
Protein Metabolism Plasma Proteins • The major plasma proteins include albumin, globulin,
and fibrinogen • Albumin contributes of colloid osmotic pressure • Globulins act in the immune response • Fibrinogen polymerizes to form blood clots
• Most plasma proteins are formed in the liver at extremely high rates (30 g/day), with the remainder - usually globulins - formed in the lymph tissues
• Plasma proteins act as a source of amino acids for the cellular needs of most tissues
• Total body protein synthesis is huge (400 g/day), establishing an equilibrium between bodily proteins and circulating plasma proteins
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Protein Metabolism Protein Utilization • Additional amino acids are utilized as a source of energy or as fat
• First, amino acids are deaminated, with the resulting amine group (-NH3) converted into urea and excreted
• Next, resulting keto acids are oxidized and enter the citric acid cycle • Alternatively, keto acids may be utilized to synthesize glucose (gluconeogenesis)
or fatty acids (ketogenesis)
• The body, lacking protein intake, will degrade approximately 20 to 30 gm of protein each day • Thus, the minimum protein intake is 20 to 30 gm per day • In times of starvation, once stored carbohydrates and fats are utilized, protein
degradation increases to 125 gm per day as the body seeks out alternative sources of energy
Liver Metabolic Functions • The liver performs vital metabolic functions for maintaining bodily homeostasis • Carbohydrate Metabolism
• Storage of glycogen • Conversion of galactose and fructose into glucose • Gluconeogenesis • Consumption of carbohydrate metabolism products
• Fat Metabolism • Oxidation of fatty acids for energy • Synthesis of cholesterol, phospholipids, and most lipoproteins • Synthesis of fat from proteins and carbohydrates
• Protein Metabolism • Deamination of amino acids • Formation of urea • Formation of plasma proteins • Interconversion of amino acids and proteins
Liver Bilirubin • The formation of bile is a major functional outcome of
the liver
• Many substances are excreted into the liver, including bilirubin • Bilirubin is a major end product of hemoglobin
degradation • Bilirubin is a valuable tool for measuring
hemolytic blood diseases as well as liver disease
• Red blood cells have a life span of approximately 120 days, when macrophages then take up the released hemoglobin • Hemoglobin is then split into globin and heme • Heme is degraded to give free iron as well as a
pyrrole nuclei from which bilirubin is formed and released into the blood by macrophages
• Bilirubin binds albumin, and the complex is transported throughout the circulation
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Liver Bilirubin • When large quantities of bilirubin collects in the
extracellular fluids, the bodily tissues including the skin turns a yellowish color known as jaundice • Normal plasma contains bilirubin at 0.5 mg/dl • Jaundice is visible at about 1.5 mg/dl, and can
increase to as high as 40 mg/dl
• Jaundice is caused by • Increased red blood cell destruction (hemolytic
jaundice), where most of the bilirubin is free • Obstruction of the bile ducts (obstructive
jaundice), where most of the bilirubin is conjugated
• In neonatal cases, the liver functions poorly and cannot conjugate significant amount of bilirubin with glucuronic acid (physiologic hyperbilirubinemia)
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Dietary Balances Introduction • The intake of carbohydrates, fats, and proteins provides energy to perform bodily
functions
• Stability of bodily weight and composition requires that energy intake must closely follow energy output • Intake too much, high levels of fat are stored and body mass increases • Intake too little, energy stores are depleted and body mass decreases
• On average, the physiologically available energy of foodstuffs are Carbohydrates 4 kcal/gram Fat 9 kcal/gram Protein 4 kcal/gram
Dietary Balances Introduction • Overall, bodily protein consumption is approximately 20 - 30 gm per day and thus an
average person must intake approximately 30 - 50 gm of protein per day
• Animal derived proteins tend to be complete, in terms of their inclusion of all essential amino acids, when compared to those derived from vegetable or grain sources
• A diet high in carbohydrates and fats will depress energy consumption from proteins
• In starvation, after carbohydrate and fat stores have been consumed, proteins stores are utilized as an energy sources
Dietary Balances Introduction • Nitrogen can be utilized to assess protein consumption
• Average protein contains 16% nitrogen by mass • Excretion of nitrogen occurs approximately 90% in urine (urea, uric acid,
creatinine) and 10% in feces • Thus, 8 gm nitrogen excreted in the urine indicates a consumption of
approximately 55 gm of protein
• Carbon dioxide can be utilized to assess carbohydrate and fat consumption • Respiratory quotient is defined as the ratio of carbon dioxide output to
oxygen usage during metabolism • Carbohydrates have a respiratory quotient of approximately 1.0 • Fats have a respiratory quotient of approximately 0.7
• Here, oxygen is consumed by excess hydrogen atoms • Thus, measuring carbon dioxide output and oxygen consumption
provides an estimate of consumption composition • As the respiratory quotient tends towards 1.0 a high carbohydrate
diet is found, as the respiratory quotient tends towards 0.7 a high fat diet is fond - note that proteins are ignored
Dietary Balances Regulation of Food Intake and Energy Storage • Intermediate and long term regulation of food intake controls the maintenance of
normal quantities of energy stores in the body
• Blood concentrations of glucose, amino acids, and lipids are key controlling mechanisms, increasing hunger as their concentrations fall, indicating glucostatic, aminostatic, and lipostatic theories of regulation
• High temperatures reduce food intake, while low temperature increase food intake due to an interaction between temperature regulating and food intake regulating systems • Increased food intake at low temperatures increases metabolic rate, thus heat
generation, and increases fat content, thus heat insulation • High fat storage increases leptin production from adipocytes, which stimulates POMC
neurons and results in a decrease fat storage due to • Decreased production NPY and AGRP • Release of α-MSH and corticotropin-releasing hormone • Increased metabolic rate and energy expenditure • Decreased insulin secretion
Dietary Balances Obesity • There have been a number of factors that have been implicated in obesity
• Sedentary lifestyle • Abnormal feeding, including both food content and eating habits • Childhood over nutrition • Neurogenic abnormalities and genetic factors
• See previous discussion of neurotransmitters involved in eating regulation
• Treatment of obesity involves the reduction of energy consumption and in the increase in energy output • Reduction in consumption of 500 kcal per day will achieve a weight loss of
approximately 1 pound per week • Reduction can be realized by a number of mechanisms
• Increase in consumption of non-nutritious substances • Drugs which attempt to decrease hunger • Drugs which alter fat metabolism, causing increased fat excretion • Increase in physical activity
Energetics Introduction • As described earlier, the consumption of carbohydrates, fats, and proteins is largely
the first step in the synthesis energy for cellular functions - and this occurs by the production of ATP • ATP contains 12,000 calories per mole under physiological conditions and can
“power” nearly all chemical reactions is the body
• ATP is the power source for many cellular functions • Protein synthesis from amino acids • Muscle contraction due to actin-myosin crossbridge formation • Molecular transport across cellular membranes by active mechanisms • Action potential transmission by the establishment of ion gradients across cell
Energetics Introduction • The most abundant source of energy in the body, however, is not
ATP but phosphocreatine which is 3 to 8 times more abundant • Phosphocreatine contains a high energy phosphate bond,
capable of producing 13,000 calories per mole under physiological conditions
• Phosphocreatine does not couple directly with chemical reactions that drive cellular functions, but acts as a buffer to maintain ATP concentration • High ATP concentrations increase phosphocreatine production • Low ATP concentrations cause phosphocreatine consumption
• The higher phosphate bond energy in phosphocreatine favors the production of ATP, while high ATP concentrations favor the retention of phosphocreatine
Energetics Metabolic Rate • A 70 kg man in bed consumes 1650 kcal per day • Eating and digestion consumes an additional 200
kcal per day • Sitting without exercising consumes an additional
150 to 400 kcal per day • Thus, a sedentary man consumes about 2000
kcal per day
• The minimal amount of energy needed to exist is defined as the basal metabolic rate (BMR) and accounts for 50 - 70% of daily energy needs in a sedentary person • Normal BMR is 65 - 70 kcal per hour • Skeletal muscle accounts for 20 - 30% of
BMR • BMR falls dramatically with age, following the
loss in skeletal muscle
Guyton & Hall. Textbook of Medical Physiology, 11th Edition
Energetics Metabolic Rate • Ingestion of food increases BMR due to the chemical reactions associated with
digestion, absorption, and storage of the food • Thermogenic effect of food, accounts for 8% of total daily energy expenditure • High carbohydrate meals increase BMR 4% • High protein meals increase BMR up to 30%
• Specific dynamic action of protein
• In response to cold, the body can engage in nonshivering thermogenesis • Here, the sympathetic nervous system releases norepinephrine and epinephrine,
causing brown fat, which is high in mitochondria content, to undergo uncoupled oxidative phosphorylation - producing heat, but little ATP
• Neonates have a high brown fat content • Adults have little brown fat content
• Note that shivering itself is a means of inducing skeletal muscle activity as a protection from cold temperatures
