Chapter 12: Bioenergetics and Regulation of Metabolism
Leptin
Leptin is a hormone secreted by fat cells that decreases appetite by suppressing orexin production. Genetic variations in the leptin molecule and its receptors have been implicated in obesity;
Respirometry
Respirometry allows accurate measurement of the respiratory quotient, which differs depending on the fuels being used by the organism. The respiratory quotient (RQ) can be measured experimentally, and can be calculated as: for the complete combustion of a given fuel source. The respiratory quotient for carbohydrates is around 1.0, while the respiratory quotient for lipids is around 0.7. In resting individuals, the respiratory quotient is generally around 0.8, indicating that both fat and glucose are consumed. The respiratory quotient changes under conditions of high stress, starvation, and exercise as predicted by the actions of different hormones.
Analysis of metabolism
There are several methods of analyzing metabolic control of an organism. In humans, levels of glucose, thyroid hormones and thyroid-stimulating hormone, insulin, glucagon, oxygen, and carbon dioxide can all be measured in the blood. Because these hormones and substrates have a predictable effect on metabolism, they can be used as indicators of metabolic function. They can also be used as indicators of disorders, as in the case of blood glucose or thyroid-stimulating hormone.
calculate the free energy change for the synthesis of ATP from cAMP and inorganic phosphate. Note: cAMP is hydrolyzed to AMP, and the free energy of hydrolysis for ATP and ADP is approximately equal.
cAMP + H2O -) AMP deltaG= -50.4 kJ/mol AMP = Pi -) ADP + H2O deltaG= 30.5 kJ/mol ADP + Pi -) ATP + H2O delta G = 30.5 kJ/mol add them all up cAMP + 2Pi -) ATP + H2O delta G= 10.6 kJ/mol
True or False: It is easier to gain weight than to lose weight.
True; the threshold is lower for uncompensated weight gain than it is for uncompensated weight loss. Therefore, it is easier to surpass this threshold and gain weight than to lose weight.
Steroid hormone ex.
cortisol
Bioenergetics
describes energy states in biological systems
Standard State conditions
25C, 1 atm, 1M
ATP structure
ATP consists of an adenosine molecule attached to three phosphate groups, and is generated from ADP and Pi with energy input from an exergonic reaction or electrochemical gradient. ATP is consumed either through hydrolysis or the transfer of a phosphate group to another molecule
ATP hydrolysis
ATP hydrolysis is most likely to be encountered in the context of coupled reactions. Many coupled reactions use ATP as an energy source. For example, the movement of sodium and potassium against their electrochemical gradients requires energy, which is harnessed from the hydrolysis of ATP.
How does coupling with ATP hydrolysis alter the energetics of a reaction?
ATP hydrolysis yields about 30 kJ/mol which can be harnessed to drive other reactions forward. This may either allow a nonspontaneous reaction to occur or increase the rate of a spontaneous reaction.
Hormonal Regulation of Metabolism
In order to make the most efficient use of the resources available, metabolism must be regulated across the entire organism. This regulation is accomplished best through hormonal means. Water-soluble peptide hormones, like insulin, are able to rapidly adjust the metabolic processes of cells via second messenger cascades, while certain fat-soluble amino acid-derivative hormones, like thyroid hormones, and steroid hormones, like cortisol, enact longer-range effects by exerting regulatory actions at the transcriptional level. Hormone levels are regulated by feedback loops with other endocrine structures, such as the hypothalamic-pituitary axis, or by the biomolecule upon which they act; for example, insulin causes a decrease in blood glucose, which removes the trigger for continued insulin release.
Peptide hormone ex.
insulin
A respiratory quotient approaching 0.7 indicates metabolism primarily of which macromolecule?
lipids The respiratory quotient (RQ) gives an indication of the primary fuel being utilized. An RQ around 0.7 indicates lipid metabolism, 0.8-0.9 indicates amino acid metabolism, (D), and 1.0 indicates carbohydrate metabolism, (A). Nucleic acids do not contribute significantly to the respiratory quotient.
−ΔS, +ΔH
non-spontaneous
Which of the following is most dependent on insulin
resting skeletal muscle Adipose tissue and resting skeletal muscle require insulin for glucose uptake. Active skeletal muscle, (A), uses creatine phosphate and glycogen (regulated by epinephrine and AMP) to maintain its energy requirements.
Glucocorticoids have been implicated in stress-related weight gain because:
they increase glucose levels, which causes insulin secretion. Short-term glucocorticoid exposure causes a release of glucose and the hydrolysis of fats from adipocytes. However, if this glucose is not used for metabolism, it causes an increase in glucose level which promotes fat storage. The net result is the release of glucose from the liver to be converted into lipids in the adipose tissue under insulin stimulation.
Amino acid derivative hormone ex.
thyroid hormones
Adding heat to a closed bio system does what
increase the internal energy of the system. increase the average of the vibrational, rotational, and translational energies. increase the enthalpy of the system.
Adenosine Diphosphate (ADP)
when one phosphate group has been removed from ATP
Adenosine Monophosphate (AMP)
when two phosphate groups has been removed from ATP
At 25°C the ΔG° for a certain reaction A⇌B+2Cis0. If the concentration of A, B, and C in the cell at 25°C are all 10 mM, how does the ΔG compare to the measurement taken with 1M concentrations?
ΔG is less thanΔG°, thus the reaction is spontaneous. See pg 753
What conditions does ΔG°′ adjust for that are not considered with ΔG°?
ΔG°′ adjusts only for the pH of the environment by fixing it at 7. Temperature and concentrations of all other reagents are still fixed at their values from standard conditions and must be adjusted for if they are not 1 M.
Phosphoric Group Transfers
ATP can provide a phosphate group as a reactant. For example, in the phosphorylation of glucose in the early stages of glycolysis, ATP donates a phosphate group to glucose to form glucose 6-phosphate. The information in Table 12.1 indicates the free energy of hydrolysis, which can be conceptualized as the transfer of the phosphate group to water. To determine the free energy of phosphoryl group transfer to another biological molecule, one could use Hess's law and calculate the difference in free energy between the reactants and products pg. 707
ATP cleavage
ATP cleavage is the transfer of a high-energy phosphate group from ATP to another molecule. Generally, this activates or inactivates the target molecule. With these phosphoryl group transfers, the overall free energy of the reaction will be determined by taking the sum of the free energies of the individual reactions.
Explain why ATP is an inefficient molecule for long-term energy storage.
ATP is an intermediate-energy storage molecule and is not energetically dense. The high- energy bonds in ATP and the presence of a significant charge make it an inefficient molecule to pack into a small space. Long-term storage molecules are characterized by energy density and stable, nonrepulsive bonds, primarily seen in lipids.
Which of the following statements is FALSE?
ATP stores are turned over more than 10,000 times daily. ATP stores are turned over about 1,000 times per day, not 10,000.
Adipose tissue
After a meal, elevated insulin levels stimulate glucose uptake by adipose tissue. Insulin also triggers fatty acid release from VLDL and chylomicrons (which carry triacylglycerols absorbed from the gut). Lipoprotein lipase, an enzyme found in the capillary bed of adipose tissue, is also induced by insulin. The fatty acids that are released from lipoproteins are taken up by adipose tissue and re-esterified to triacylglycerols for storage. The glycerol phosphate required for triacylglycerol synthesis comes from glucose that is metabolized in adipocytes as an alternative product of glycolysis. Insulin can also effectively suppress the release of fatty acids from adipose tissue. During the fasting state, decreased levels of insulin and increased epinephrine activatehormone-sensitive lipase in fat cells, allowing fatty acids to be released into circulation.
Brain
Although the brain represents only 2 percent of total body weight, it obtains 15 percent of the cardiac output, uses 20 percent of the total O2, and consumes 25 percent of the total glucose, the brain's primary fuel. Blood glucose levels are tightly regulated to maintain a sufficient glucose supply for the brain (and sufficient concentration while studying). Normal function depends on a continuous glucose supply from the bloodstream. In hypoglycemic conditions (<70.g/dL) hypothalamic centers in the brain sense a fall in blood glucose level, and the release of glucagon and epinephrine is triggered. Fatty acids cannot cross the blood-brain barrier and are therefore not used at all as an energy source. Between meals, the brain relies on blood glucose supplied by either hepatic glycogenolysis or gluconeogenesis. Only during prolonged fasting does the brain gain the capacity to use ketone bodies for energy, and even then, the ketone bodies only supply approximately two-thirds of the fuel; the remainder is glucose.
What is an advantage of analyzing the half-reactions in biological oxidation and reduction reactions?
Analyzing half-reactions can help to determine the number of electrons being transferred. This type of analysis also facilitates balancing equations and the determination of electrochemical potential if reduction potentials are provided.
Provide an example of disequilibrium that is maintained at the expense of cellular energy.
Any excitable cell is maintained in a state of disequilibrium. Classic examples include muscle tissue and neurons. In addition, cell volume and membrane transport are regulated by the action of the sodium-potassium pump, which can maintain a stable disequilibrium state in most tissues.
How is the respiratory quotient expected to change when a person transitions from resting to brief exercise?
As a person begins to exercise, the proportion of energy derived from glucose increases. This transition to almost exclusively carbohydrate metabolism will cause the respiratory quotient to approach 1.
Modified Standard State
Biochemical analysis works well under all standard conditions except one: pH. A 1 Mconcentration of protons would correspond to a pH of 0, which is far too acidic for most biochemical reactions. Therefore, in the modified standard state, [H+] = 10−7 M and the pH is 7. With this additional condition, ΔG° is given the special symbol ΔG°′, indicating that it is standardized to the neutral buffers used in biochemistry. Note that if the concentrations of other reactants and products differ from 1 M, these must still be adjusted for in the equation above. The shift in ΔG as a result of changing concentration is not universally toward or away from spontaneity. There is a general trend that reactions with more products than reactants have a more negative ΔG, while reactions with more reactants than products have a more positive ΔG. While this trend is useful for making quick assessments, always double check with numbers on Test Day.
Open system
Biological systems are often considered open systems because they can exchange both energy and matter with the environment. Energy is exchanged in the form of mechanical work when something is moved over a distance, or as heat energy. Matter is exchanged through food consumption and elimination, as well as respiration.
Body Mass Index
Body mass can be measured and tracked using the body mass index (BMI), which is given by: where mass is measured in kilograms and height is measured in meters. A normal BMI is considered to be between 18.5 and 25; values lower than this are considered underweight. A BMI between 25 and 30 is considered overweight, whereas a BMI over 30 is considered obese.
In the absence of oxygen which tissue will experience most damage
Brain The brain uses aerobic metabolism of glucose exclusively and therefore is very sensitive to oxygen levels. The extremely high oxygen requirement of the brain (20% of the body's oxygen content) relative to its size (2% of total body weight) implies that brain is the most sensitive organ to oxygen deprivation.
Calorimeters
Calorimeters can measure basal metabolic rate (BMR) based on heat exchange with the environment. Human calorimetry makes use of large insulated chambers with specialized heat sinks to determine energy expenditure. Because of the isolationist nature of testing and the expense of creating a calorimetry chamber, other measures of BMR are preferred. Because of previous experimentation, BMR can be estimated based on age, weight, height, and gender.
Catecholamines
Catecholamines are secreted by the adrenal medulla and include epinephrine andnorepinephrine, also known as adrenaline and noradrenaline. Catecholamines increase the activity of liver and muscle glycogen phosphorylase, thus promoting glycogenolysis. This increases glucose output by the liver. Glycogenolysis also increases in skeletal muscle, but because muscle lacks glucose-6- phosphatase, glucose cannot be released by skeletal muscle into the bloodstream; instead, it is metabolized by the muscle tissue itself. Catecholamines act on adipose tissue to increase lipolysis by increasing the activity of hormone-sensitive lipase. Glycerol from triacylglycerol breakdown is a minor substrate for gluconeogenesis. Epinephrine also acts directly on target organs like the heart to increase the basal metabolic rate through the sympathetic nervous system. This increase in metabolic function is often associated with an adrenaline rush.
What tissue is least able to change its fuel source in periods of prolonged starvation?
Cells that rely solely on anaerobic respiration are the least adaptable to different energy sources. Therefore, red blood cells are the least flexible during periods of prolonged starvation and stay reliant on glucose.
Entropy
Changes in entropy (ΔS) measure the degree of disorder or energy dispersion in a system. Units: J/K
Free energy
Changes in free energy (ΔG) provide information about chemical reactions and can predict whether a chemical reaction is favorable and will occur. In biological systems, ATP plays a crucial role in transferring energy from energy-releasing catabolic processes to energy-requiring anabolic processes.
Which of the following side effects would be anticipated in someone taking leptin to promote weight loss
Drowsiness Leptin acts to decrease appetite by inhibiting the production of orexin. Orexin is also associated with alertness, so decreasing the level of orexin in the body is expected to cause drowsiness. Even without this information, the answer should be apparent because the body tends to maintain an energy balance. If consumption decreases, energy expenditures are expected to decrease as well.
During what stage is there the greatest decrease in the circulating concentration of insulin?
During the postabsorptive state, there is the greatest decrease in insulin levels. The concentrations of the counterregulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, and growth hormone) begin to rise.
Cytochromes
Electron transport chain
Ubiquinone (CoQ)
Electron transport chain
Enthalpy
Enthalpy measures the overall change in heat of a system during a reaction. At constant pressure and volume, enthalpy (ΔH) and thermodynamic heat exchange (Q) are equal.
Which process is expected to begin earliest in a prolonged fast?
Enzyme phosphorylation and dephosphorylation. A prolonged fast is characterized by an increase in glucagon, which accomplishes its cellular activity by phosphorylating and dephosphorylating metabolic enzymes. Glycogen storage,(B), is then halted, but this requires enzyme regulation by glucagon to occur. Later in the postabsorptive state, protein breakdown, (C), begins. Eventually, in starvation, ketone bodies, (A), are used by the brain for its main energy source.
True or False: Body mass can be predicted by the leptin receptor phenotype and caloric intake alone.
False; energy expenditure, genetics, socioeconomic status, geography, and other hormones also play a role in body mass regulation.
Flavoproteins
Flavoproteins contain a modified vitamin B2, or riboflavin. They are nucleic acid derivatives, generally either flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). Flavoproteins are most notable for their presence in the mitochondria and chloroplasts as electron carriers. Flavoproteins are also involved in the modification of other B vitamins to active forms. Finally, flavoproteins function as coenzymes for enzymes in the oxidation of fatty acids, the decarboxylation of pyruvate, and the reduction of glutathione.
Ghrelin
Ghrelin is secreted by the stomach in response to signals of an impending meal. Sight, sound, taste, and especially smell all act as signals for its release. Ghrelin increases appetite and also stimulates secretion of orexin.
Glucagon
Glucagon is a peptide hormone secreted by the α-cells of the pancreatic islets of Langerhans The primary target for glucagon action is the hepatocyte. Glucagon acts through second messengers to cause the following effects: -Increased liver glycogenolysis. Glucagon activates glycogen phosphorylase and inactivates glycogen synthase. -Increased liver gluconeogenesis. Glucagon promotes the conversion of pyruvate to phosphoenolpyruvate by pyruvate carboxylase and phosphoenolpyruvate carboxykinase(PEPCK). Glucagon increases the conversion of fructose 1,6-bisphosphate to fructose 6- phosphate by fructose-1,6-bisphosphatase. -Increased liver ketogenesis and decreased lipogenesis. -Increased lipolysis in the liver. Glucagon activates hormone-sensitive lipase in the liver. Because the action is on the liver and not the adipocyte, glucagon is not considered a major fat-mobilizing hormone. --- Low plasma glucose (hypoglycemia) is the most important physiological promoter of glucagon secretion, and elevated plasma glucose (hyperglycemia) is the most important inhibitor. Amino acids, especially basic amino acids (arginine, lysine, histidine), also promote the secretion of glucagon. Thus, glucagon is secreted in response to the ingestion of a meal rich in proteins.
Postabsorptive (Fasting) state
Glucagon, cortisol, epinephrine, norepinephrine, and growth hormone oppose the actions of insulin. These hormones are sometimes termed counterregulatory hormones because of their effects on skeletal muscle, adipose tissue, and the liver, which are opposite to the actions of insulin. In the liver, glycogen degradation and the release of glucose into the blood are stimulated, as shown in Figure 12.3. Hepatic gluconeogenesis is also stimulated by glucagon, but the response is slower than that of glycogenolysis. Whereas glycogenolysis begins almost immediately at the beginning of the postabsorptive state, gluconeogenesis takes about 12 hours to hit maximum velocity. The release of amino acids from skeletal muscle and fatty acids from adipose tissue are both stimulated by the decrease in insulin and by an increase in levels of epinephrine. Once carried into the liver, amino acids and fatty acids can provide the necessary carbon skeletons and energy required for gluconeogenesis.
Glucocorticoids
Glucocorticoids from the adrenal cortex are responsible for part of the stress response. In order to make a getaway in the "fight-or-flight" response, glucose must be rapidly mobilized from the liver in order to fuel actively contracting muscle cells while fatty acids are released from adipocytes. Glucocorticoids, especially cortisol, are secreted with many forms of stress, including exercise, cold, and emotional stress. Cortisol, is a steroid hormone that promotes the mobilization of energy stores through the degradation and increased delivery of amino acids and increased lipolysis. Cortisol also elevates blood glucose levels, increasing glucose availability for nervous tissue through two mechanisms. First, cortisol inhibits glucose uptake in most tissues (muscle, lymphoid, and fat) and increases hepatic output of glucose via gluconeogenesis, particularly from amino acids. Second, cortisol has a permissive function that enhances the activity of glucagon, epinephrine, and other catecholamines. Long- term exposure to glucocorticoids may be required clinically, but causes persistent hyperglycemia, which stimulates insulin. This actually promotes fat storage in the adipose tissue, rather than lipolysis.
NADH
Glycolysis, fermentation, citric acid cycle, electron transport chain
Homeostasis
Homeostasis is a physiological tendency toward a relatively stable state that is maintained and adjusted, often with the expenditure of energy. Most compounds in the body are actually maintained at a homeostatic level that is different from equilibrium, which allows us to store potential energy; for example, keeping sodium concentrations much higher outside a neuron than inside it creates a gradient that stores energy. In this state, reactions can proceed such that equilibrium is put off for a long time (someone born today can delay equilibrium for about 80 years).
How do hormonal controls of glycogen metabolism differ from allosteric controls?
Hormonal control is systemic and covalent. Hormonal controls are coordinated to regulate the metabolic activity of the entire organism, while allosteric controls can be local or systemic. The modification of the enzymes of glycogen metabolism by insulin and glucagon is either through phosphorylation or dephosphorylation, both of which modify covalent bonds.
Insulin
Insulin is a peptide hormone secreted by the β-cells of the pancreatic islets of Langerhans It is a key player in the uptake and storage of glucose. Glucose is absorbed by peripheral tissues via facilitated transport mechanisms that utilize glucose transporters located in the cell membrane. The tissues that require insulin for effective uptake of glucose are adipose tissue and resting skeletal muscle. Tissues in which glucose uptake is not affected by insulin include: -Nervous tissue -Kidney tubules -Intestinal mucosa -Red blood cells (erythrocytes) -β-cells of the pancreas Insulin impacts the metabolism of the different nutrient classes in different ways. For carbohydrates, insulin increases the uptake of glucose and increases carbohydrate metabolism in muscle and fat. Increased glucose in muscle can be used as additional fuel to burn during exercise, or can be stored as glycogen. Insulin also increases glycogen synthesis in the liver by increasing the activity of glucokinase and glycogen synthase, while decreasing the activity of enzymes that promote glycogen breakdown (glycogen phosphorylase and glucose-6- phosphatase). While the primary effects of insulin are on carbohydrate metabolism, it also changes the way that the body processes other macromolecules. For instance, insulin increases amino acid uptake by muscle cells, thereby increasing levels of protein synthesis and decreasing breakdown of essential proteins. Insulin also exhibits a significant impact on the metabolism of fats, especially in the liver and adipocytes. --- The effects of insulin on the metabolism of fats Insulin increases: -Glucose and triacylglycerol uptake by fat cells -Lipoprotein lipase activity, which clears VLDL and chylomicrons from the blood -Triacylglycerol synthesis (lipogenesis) in adipose tissue and the liver from acetyl-CoA Insulin decreases: -Triacylglycerol breakdown (lipolysis) in adipose tissue -Formation of ketone bodies by the liver The most important controller of insulin secretion is plasma glucose. Above a threshold of 100 mg/dL or about 5.6 mM glucose, insulin secretion is directly proportional to plasma glucose. For glucose to promote insulin secretion, it must not only enter the β-cell but also be metabolized, increasing intracellular ATP concentration. Increased ATP leads to calcium release in the cell, which promotes exocytosis of preformed insulin from intracellular vesicles. Insulin secretion is also affected by signaling initiated by other hormones, such as glucagon and somatostatin.
Functional Relationship of Glucagon and Insulin
Insulin, associated with a well-fed, absorptive metabolic state, and glucagon, associated with a postabsorptive metabolic state, usually oppose each other with respect to pathways of energy metabolism. Enzymes that are phosphorylated by glucagon are generally dephosphorylated by insulin; enzymes that are phosphorylated by insulin are generally dephosphorylated by glucagon. Figure 12.6 displays a feedback diagram of the interaction of insulin and glucagon on plasma glucose concentration, as well as fat and protein metabolism.
Describe the primary metabolic function of each of the following hormones:
Insulin: Insulin promotes glucose uptake by adipose tissue and muscle, glucose utilization in muscle cells, and macromolecule storage (glycogenesis, lipogenesis). Glucagon: Glucagon increases blood glucose levels by promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis. Cortisol: Cortisol increases lipolysis and amino acid mobilization, while decreasing glucose uptake in certain tissues and enhancing the activity of other counterregulatory hormones. Catecholamines: Catecholamines increase glycogenolysis in muscle and liver and lipolysis in adipose tissue. Thyroid Hormones (T3/T4): Thyroid hormones increase basic metabolic rate and potentiate the activity of other hormones.
With prolonged fasting, the brain can turn to which alternative fuel for energy?
Ketone bodies
Prolonged Fasting (Starvation)
Levels of glucagon and epinephrine are markedly elevated during starvation. Increased levels of glucagon relative to insulin result in rapid degradation of glycogen stores in the liver. As liver glycogen stores are depleted, gluconeogenic activity continues and plays an important role in maintaining blood glucose levels during prolonged fasting; after about 24 hours, gluconeogenesis is the predominant source of glucose for the body. Lipolysis is rapid, resulting in excess acetyl-CoA that is used in the synthesis of ketone bodies. Once levels of fatty acids and ketones are high enough in the blood, muscle tissue will utilize fatty acids as its major fuel source and the brain will adapt to using ketones for energy. After several weeks of fasting, the brain derives approximately two-thirds of its energy from ketones and one-third from glucose. The shift from glucose to ketones as the major fuel reduces the quantity of amino acids that must be degraded to support gluconeogenesis, which spares proteins that are vital for other functions. Cells that have few, if any, mitochondria, like red blood cells, continue to be dependent on glucose for their energy.
Adenosine Triphosphate (ATP)
Major energy currency in the body formed from substrate-level phosphorylation as well as oxidative phosphorylation Why do we want ATP to be a mid-level carrier and not a higher-level one? Think about your wallet. If you never had the ability to get change back after a purchase, what type of bill would you want in abundance? One dollar bills! Similarly, ATP cannot get back the "leftover" free energy after a reaction, so it's best to use a carrier with a smaller free energy. ATP provides about 30 kJ/mol of energy under physiological conditions If a reaction only requires 10 kJ/mol to overcome a positive ΔG value, then 20 kJ/mol have been wasted. The waste would be even higher with a higher-energy compound like creatine phosphate.
Closed System -internal energy (U)
Most biochemical studies are performed on the cellular or subcellular level rather than in an entire organism. These systems can be considered closed because there is no exchange of matter with the environment. In such a system, we can make useful simplifications about the internal energy, U. Internal energy is the sum of all of the different interactions between and within atoms in a system; vibration, rotation, linear motion, and stored chemical energies all contribute. Because the system is closed, the change in internal energy can come only in the form of work or heat. This can be represented mathematically through the First Law of Thermodynamics, ΔU = Q - W. Work in thermodynamics refers to changes in pressure and volume. These are constant in most living systems, so the only quantity of interest in determining internal energy is heat.
The reduction half-reaction in the last step of the electron transport chainis:
O2+ 4e-+ 4 H+→2 H2O Reduction is a gain of electrons, which eliminates (B) because it is an oxidation reaction NADPH, (C), is a product of the pentose phosphate pathway. Ubiquinone, (D), transfers electrons during the course of the electron transport chain, but is not the final electron acceptor. This title belongs to oxygen.
Orexin
Orexin further increases appetite, and is also involved in alertness and the sleep-wake cycle. Hypoglycemia is also a trigger for orexin release
Glutathione
Oxidative stress
NADPH
Pentose phosphate pathway, lipid biosynthesis, bleach formation, oxidative stress, photosynthesis
What energy state was described in the introduction to this chapter?
Postabsorptive Skipping a single meal is not a prolonged fast. However, the increase in hormones that promote gluconeogenesis and glycogenolysis indicates that the absorptive phase has ended.
Fast-twitch muscle fibers have a high capacity for anaerobic glycolysis but are quick to fatigue. They are involved primarily in short-term, high-intensity exercise. Slow-twitch muscle fibers in arm and leg muscles are well vascularized and primarily oxidative. They are used during prolonged, low-to-moderate intensity exercise and resist fatigue. Slow- twitch fibers and the number of their mitochondria increase dramatically in trained endurance athletes.
Slow twitch= red Fast twitch= white
What organ consumes the greatest amount of glucose relative to its percentage of body mass?
The brain consumes the greatest amount of glucose relative to its percentage of body mass.
Why can heat be used as a measure of internal energy in living systems?
The cellular environment has a relatively fixed volume and pressure, which eliminates work from our calculations of internal energy; if ΔU = Q - W and W = 0, ΔU = Q.
Which of the following statements is true about the hydrolysis of ATP?
The free energy of hydrolysis of ATP is nearly the same as for ADP. The hydrolysis of ATP is energetically favorable because there are repulsive negative charges that are relieved when hydrolyzed, and the new compounds are stabilized by resonance. This is true of both ATP and ADP. Some of the other answer choices are tempting, though. In (A), ATP hydrolysis relies on pH because a protonated ATP molecule contains less negative charge and therefore experiences less repulsive force. For (B), the energy released by one mole of creatine phosphate upon hydrolysis is not sufficient to phosphorylate two moles of ADP according to Table 12.1; creatine phosphate donates one phosphate group to a molecule of ADP, so one mole of creatine phosphate will phosphorylate one mole of ADP. For (D), the removal of two phosphate groups from ATP yields AMP, not cyclic AMP.
Describe the major metabolic functions of the liver.
The liver is responsible for maintaining a steady-state concentration of glucose in the blood through glucose uptake and storage, glycogenolysis, and gluconeogenesis. The liver also participates in cholesterol and fat metabolism, the urea cycle, bile synthesis, and the detoxification of foreign substances.
Resting Muscle
The major fuels of skeletal muscle are glucose and fatty acids. Because of its enormous bulk, skeletal muscle is the body's major consumer of fuel. After a meal, insulin promotes glucose uptake in skeletal muscle, which replenishes glycogen stores and amino acids used for protein synthesis. Both excess glucose and amino acids can also be oxidized for energy. In the fasting state, resting muscle uses fatty acids derived from free fatty acids circulating in the bloodstream. Ketone bodies may also be used if the fasting state is prolonged.
If you were designing a study to assess metabolism, which measurement method would you choose? Defend your answer.
The methods described in the text include chemical analysis, which is objective and can quantify specific metabolic substrates, products, and enzymes; calorimetry, which is most accurate for basal metabolic rate but also most expensive; respirometry, which provides basic information about fuel sources; and caloric analysis at constant weight (food and exercise logs), which is the least invasive. Any of these answers could be defended.
Postprandial (Absorptive State)
The postprandial state, also called the absorptive or well-fed state, occurs shortly after eating. This state is marked by greater anabolism (synthesis of biomolecules) and fuel storage than catabolism (breakdown of biomolecules for energy). Nutrients flood in from the gut and make their way via the hepatic portal vein to the liver, where they can be stored or distributed to other tissues of the body. The postprandial state generally lasts three to five hours after eating a meal. Just after eating, blood glucose levels rise and stimulate the release of insulin. The three major target tissues for insulin are the liver, muscle, and adipose tissue, as shown in Figure 12.2. Insulin promotes glycogen synthesis in liver and muscle. After the glycogen stores are filled, the liver converts excess glucose to fatty acids and triacylglycerols. Insulin promotes triacylglycerol synthesis in adipose tissue and protein synthesis in muscle, as well as glucose entry into both tissues. After a meal, most of the energy needs of the liver are met by the oxidation of excess amino acids. Two types of cells—nervous tissue and red blood cells—are notably insensitive to insulin. Nervous tissue derives energy from oxidizing glucose to CO2 and water in both the well-fed and normal fasting states. Only in prolonged fasting does this situation change. Red blood cells can only use glucose anaerobically for all their energy needs, regardless of the individual's metabolic state.
What is the preferred fuel for most cells in the well-fed state? What is the exception and its preferred fuel?
The preferred fuel for most cells in the well-fed state is glucose; the exception is cardiac muscle, which prefers fatty acids.
Active Muscle
The primary fuel used to support muscle contraction depends on the magnitude and duration of exercise as well as the major fibers involved. A very short-lived source of energy (2-7 seconds) comes from creatine phosphate, which transfers a phosphate group to ADP to form ATP. Skeletal muscle has stores of both glycogen and some triacylglycerols. Blood glucose and free fatty acids may also be used. Short bursts of high-intensity exercise are also supported by anaerobic glycolysis drawing on stored muscle glycogen. During moderately high-intensity, continuous exercise, oxidation of glucose and fatty acids are both important, but after 1 to 3 hours of continuous exercise at this level, muscle glycogen stores become depleted, and the intensity of exercise declines to a rate that can be supported by oxidation of fatty acids.
High-energy electron carriers
These are all soluble and include NADH, NADPH, FADH2, ubiquinone, cytochromes, and glutathione. Some of these electron carriers are used by the mitochondrial electron transport chain, which leads to the oxidative phosphorylation of ADP to ATP. As electrons are passed down the electron transport chain, they give up their free energy to form the proton-motive force across the inner mitochondrial membrane. In addition to soluble electron carriers, there are membrane-bound electron carriers embedded within the inner mitochondrial membrane. One such carrier is flavin mononucleotide (FMN), which is bonded to complex I of the electron transport chain and can also act as a soluble electron carrier. In general, proteins with prosthetic groups containing iron-sulfur clusters are particularly well suited for the transport of electrons.
First Law of thermodynamics
This can be represented mathematically through the First Law of Thermodynamics, ΔU = Q - W. Work in thermodynamics refers to changes in pressure and volume. These are constant in most living systems, so the only quantity of interest in determining internal energy is heat.
Thyroid Hormones
Thyroid hormone activity is largely permissive. In other words, thyroid hormone levels are kept more or less constant, rather than undulating with changes in metabolic state. Thyroid hormones increase the basal metabolic rate, as evidenced by increased O2 consumption and heat production when they are secreted. The increase in metabolic rate produced by a dose of thyroxine (T4) occurs after a latency of several hours but may last for several days, while triiodothyronine (T3) produces a more rapid increase in metabolic rate and has a shorter duration of activity. The subscript numbers refer to the number of iodine atoms in the hormone; iodine atoms are represented by purple spheres in the structures shown in Figure 12.10. T4 can be thought of as the precursor to T3; deiodonases (enzymes that remove iodine from a molecule) are located in target tissues and convert T4 to T3. Thyroid hormones have their primary effects in lipid and carbohydrate metabolism. They accelerate cholesterol clearance from the plasma and increase the rate of glucose absorption from the small intestine. Epinephrine requires thyroid hormones to have a significant metabolic effect.
Thyroid storm is a potentially lethal state of extreme hyperthyroidism in which T3 and T4 levels are significantly above normal limits. What vital sign abnormalities might be expected in a patient with thyroid storm?
Thyroid storm presents with hyperthermia (high temperature), tachycardia (fast heart rate), hypertension (high blood pressure), and tachypnea (high respiratory rate).
Tissue Specific Metabolism
Tissues have evolved so that their metabolic needs are met in a way corresponding to their form and function. The major sites of metabolic activity in the body are the liver, skeletal and cardiac muscles, brain, and adipocytes. Connective tissue and epithelial cells do not make major contributions to the consumption of energy. Remember though, that epithelial cells are the primary secretory cells, so they are involved in the regulation of metabolism. We have already discussed how the body operates under different nutritional conditions.
Liver
Two major roles of the liver in fuel metabolism are to maintain a constant level of blood glucose under a wide range of conditions and to synthesize ketones when excess fatty acids are being oxidized. After a meal, glucose concentration in the portal blood is elevated. The liver extracts excess glucose and uses it to replenish its glycogen stores. Any glucose remaining in the liver is then converted to acetyl-CoA and used for fatty acid synthesis. The increase in insulin after a meal stimulates both glycogen synthesis and fatty acid synthesis in the liver. The fatty acids are converted to triacylglycerols and released into the blood as very-low-density lipoproteins(VLDL). In the well-fed state, the liver derives most of its energy from the oxidation of excess amino acids. Between meals and during prolonged fasts, the liver releases glucose into the blood. The increase in glucagon during fasting promotes both glycogen degradation and gluconeogenesis. Lactate from anaerobic metabolism, glycerol from triacylglycerols, and amino acids provide carbon skeletons for glucose synthesis.
Cardiac Muscle
Unlike other tissues of the body, cardiac myocytes prefer fatty acids as their major fuel, even in the well-fed state. When ketones are present during prolonged fasting, they can also be used. Thus, not surprisingly, cardiac myocytes most closely parallel skeletal muscle during extended periods of exercise. In patients with cardiac hypertrophy (thickening of the heart muscle), this situation reverses to some extent. In a failing heart, glucose oxidation increases and β-oxidation falls.
What makes ATP such a good energy carrier?
What makes ATP such a good energy carrier is its high-energy phosphate bonds. The negative charges on the phosphate groups experience repulsive forces with one another, and the ADP and Pi molecules that form after hydrolysis are stabilized by resonance. While ATP doesn't rapidly break down on its own in the cell, it is much more stable after hydrolysis. This accounts for the very negative value of ΔG. Under standard conditions ΔG° is about -55 kJ/mol At pH 7 and with excess magnesium, the standard free energy change is still -30.5 kJ/mol ADP, which also displays charge repulsion and resonance stabilization after hydrolysis, has similar ΔG values, but AMP has a much smaller ΔG° near -9.2 kJ/mol
Gibbs free energy Equation
When combined together mathematically, along with temperature (T), these quantities (enthalpy and entropy) can be related through the Gibbs free energy equation: ΔG=ΔH−TΔS which predicts the direction in which a chemical reaction proceeds spontaneously. Spontaneous reactions proceed in the forward direction, exhibit a net loss of free energy, and therefore have a negative ΔG. In contrast, nonspontaneous reactions, which would be spontaneous in the reverse direction, exhibit a net gain of energy and have a positive ΔG. Free energy approaches zero as the reaction proceeds to equilibrium and there is no net change in concentration of reactants or products.
Adding heat to a closed biological system will do all of the following EXCEPT:
cause the system to do work to maintain a fixed internal energy. In a closed biological system, enthalpy, heat, and internal energy are all directly related because there is no change in pressure or volume. Because pressure and volume are fixed, work cannot be done, thus (C) is correct.
The ability to exist in both an oxidized and a reduced state is characteristic of:
electron carriers. In order to transport electrons, electron carriers like flavoproteins must be able to exist in a stable oxidized state and a stable reduced form. ATP can be dephosphorylated but is generally not oxidized or reduced. Regulatory enzymes may also be phosphorylated or dephosphorylated but are not generally oxidized or reduced.
Counterregulatory hormones
glucagon, epinephrine, norepinephrine, growth hormone, cortisol
+ΔS, −ΔH
spontaneous at all temp
+ΔS, +ΔH
spontaneous at high temp
−ΔS, −ΔH
spontaneous at low temp
Change in free energy
standard free energy (ΔG°) is the energy change that occurs at standard concentrations of 1 M, pressure of 1 atm, and temperature of 25°C where R is the universal gas constant, T is the temperature, and Q is the reaction quotient.
