Ch. 12: Bioenergetics and Regulation of Metabolism Flashcards
why are biological systems often considered open systems?
because they can exchange both energy and matter with the environment
in the body, how is energy exchanged? how is matter exchanged?
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
at what level are most biochemical studies performed?
cellular or subcellular, NOT the entire organism
why are the cellular or subcellular studies considered closed systems?
there is no exchange of matter with the environment
defn: internal energy
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)
how does the fact that the system is closed affect the change in internal energy?
it can come only in the form of work (changes in pressure and volume) or heat
why is heat the only quantity of interest in determining internal energy?
because pressure and volume (which together are work) are constant in most living systems
defn: bioenergetics
the term used to describe energy states in bilogical systems
what information do changes in free energy (G) provide? (2)
- info about chemical reactions
- can predict whether a chem reaction is favorable and will occur
in biological systems, what is the crucial role that ATP plays?
crucial role in transferring energy from energy-releasing catabolic processes to energy-requiring anabolic processes
what determines whether a chemical reaction proceeds?
by the degree to which enthalpy and entropy change during a chemical reaction
defn: enthalpy
measures the overall change in heat of a system during a reaction
what is true about change in enthalpy (H) and thermodynamic heat exchange (Q) at constant pressure and volume?
they are equal
defn: changes in entropy (S)
measure the degree of disorder or energy dispersion in a system
unit: entropy
J/K
eqn + func: Gibbs free energy equation
predicts the direction in which a chemical reaction proceeds spontaneously
char: spontaneous vs. nonspontaneous reactions vs. equilibrium
SPONTANEOUS = proceed forward, exhibit a net loss of free energy, have negative deltaG
NONSPONTANEOUS = would be spontaneous in reverse, have net gain of energy, positive deltaG
APPROACHING EQUILIBRIUM = free energy approaches zero, no net change in concentration of reactants or products
defn: change in free energy vs. change in standard free energy
CHANGE IN FREE ENERGY = predicts changes occurring at any concentration of products and reactants and at any temperature
STANDARD FREE ENERGY = the energy change that occurs at standard concentrations of 1 M, pressure of 1 atm, temperature of 25 deg C
how can change in free energy and change in standard free energy be related? (eqn)
where R is the universal gas constant
T is temperature
Q is the reaction quotient
biochemical analysis works well under all standard conditions except one, what is that one?
pH
values: modified standard state
ΔG°′ indicates that it is standardized to the neutral buffers used in biochem
what is the general trend of the relationship between deltaG and the ratio of products to reactants?
products > reactants tend to have more negative deltaG
reactants > products tend to have more positive deltaG
the human body can make use of different energy sources with roughly the same efficiency, so are all nutrient molecules created equally?
no (i.e fats are more energy-rich than carbohydrates, proteins, or ketones)
value of energy: complete combustion of fat vs. carbohydrates, proteins, or ketones
fat: 9 kcal/g of energy
others: 4 kcal/g
why are fats preferred for long-term energy storage?
fats are so much more energy-dense than other biomolecules
analogy: fats vs. carbs for storage
fats = 16 GB flash drive
carbs = 8 GB flash drive
they occupy the same amount of physical space, but fat holds twice as much data
what is the readily available form of energy fot the cell?
ATP! (adenosine triphosphate)
what is ATP formed from?
substrate-level phosphorylation and 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
main source of production for ATP + 2 secondary sources
main: mitochondrial ATP synthase
secondary: 1. during glycolysis 2. indirectly from GTP in the citric acid cycle
structure + generated from + consumed by: ATP
- consists of an adenosine molecule attached to 3 phosphate groups
- generated from ADP and Pi with energy input from an exergonic reaction or electrochemical gradient
- consumed either through hydrolysis or the transfer of a phosphate group to another molecule
what results if one phosphate is removed from ATP? if 2 phosphates are removed from ATP?
1 phosphate –> adenosine diphosphate (ADP) is produced
2 phosphates –> adenosine monophosphate (AMP) produced
in a single day, what % of a person’s body weight does an average sized person use in ATP? how many grams of ATP are available at any given time?
what accounts for this discrepancy?
90%
50g
continuous recycling of ATP, ADP, and Pi more than 1000 times per day accounts for this discrepancy
func (2): ATP
to fuel energetically unfavorable reactions or to activate or inactive other molecules
it is the major energy currency in the body and is a mid-level energy carrier
what makes ATP such a good energy carrier? + how
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
is ATP more stable before or after hydrolysis? what thermodynamic value does this acccount for?
after, although its not UNSTABLE before hand
accounts for the negative value of deltaG
values: deltaGknot for
standard conditions
at pH 7 and with excess magnesium
ADP
AMP
standard conditions: - 55 kJ/mol
at pH 7 and excess magnesium: - 30.5 kJ/mol
ADP similar to above
AMP: -9.2 kJ/mol
in what reaction layout is ATP hydrolysis most likely to be in countered?
in the context of coupled reactions
how is ATP used in many coupled reactions?
as an energy source
defn: ATP cleavage
the transfer of a high-energy phosphate group from ATP to another molecule which generally activates or inactivates the target molecule
how is the overall free energy of the reaction determined with the phosphoryl group transfers that happen with ATP cleavage?
by taking the sum of the free energies of the individual reactions
how can we conceptualize the free energy of hydrolysis?
the transfer of the phosphate group to water
how can one determine the free energy of the phosphoryl group transfer to another biological molecule?
use Hess’s law and calculate the difference in free energy between the reactants and products
true or false: many key enzymes in ATP synthesis and other biochemical pathways have oxidoreductase activity
true
sign of delta G and E for spontaneous redox reactions
negative deltaG
positive E (electromotive force)
what are 6 molecules that act as soluble, high-energy electron carriers in the cytoplasm?
- NADH
- NADPH
- FADH2
- ubiquinone
- cytochromes
- gluatathione
what happens to electrons as they are passed down the electron transport chain?
they give up their free energy to form the proton-motive force across the inner mitochondrial membrane
are their electron carriers other than the soluble ones we have just discussed?
yes there are also membrane-bound electron carriers embedded within the inner mitochondrial membrane
what is an example of an inner mitochondrial membrane bound electron carrier
flavin mononucleotide (FMN), which is bonded to complex I of the ETC and can also act as a soluble electron carrier
proteins with prosthetic groups containing iron-sulfur clusters are particularly well suited for what
the transport of electrons
defn: riboflavin
a modified vitamin B2 contained in flavoproteins
defn: flavoproteins
nucleic acid derivatives
generally either flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN)
what are flavoproteins most notable for?
their presence in the mitochondria and chloroplasts as electron carriers
2 other funcs: flavoproteins
- involved in the modification of other B vitamins to active forms
- function as coenzymes for enzymes in the oxidation of fatty acids, the decarboxylation of pyruvate, and the reduction of glutathione
what is one of the key differences between general chemistry and biochemistry?
whether or not equilibrium is seen as a desirable state
biochemists: no
what do biochemists seek instead of equilibrium?
homeostasis
defn: equilibrium vs. homeostasis
equilibrium = a fixed state, thus preventing us from storing any energy for later use or creating an excitable environment
homeostasis = a physiological tendency toward a relatively stable stat that is maintained and adjusted, often with the expenditure of energy
what is the impact of the fact that most compounds in the body are actually maintained at a homeostatic level that is different from equilibrium?
we can store potential energy
reactions can proceed such that equilibrium is put off for a long time
what do the pathways that are operational in fuel metabolism depend on?
the nutritional status of the organism
what 2 things are very pronounced when going from the well-fed state to an overnight fast?
- shifts between storage and mobilization of a particular fuel
- shifts among the types of fuel being used
2 aka + defn: + char postprandial state
aka: absorptive state, well-fed state
occurs shortly after eating and generally lasts 3-5 hours after eating a meal
marked by greater anabolism and fuel storage than catabolism
defn: anabolism vs. catabolism
anabolism = synthesis of biomolecules
catabolism = breakdown of biomolecules for energy
what happens during the postprandial state?
nutrients flood fro 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
what happens just after eating? (4)
- blood glucose levels rise and stimulate the release of insulin
- 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 the adipose tissue and protein synthesis in muscle, as well as glucose entry into both tissues
what are the 3 major target tissues for insulin?
- the liver
- muscle
- adipose tissue
after a meal, how are most of the energy needs of the liver met?
by the oxidation of excess amino acids
what 2 types of cells are notably insensitive to insulin?
- nervous tissue
- red blood cells
how do nervous tissue and red blood cells interact with glucose?
NERVOUS TISSUE derives energy fro oxidizing glucose to CO2 and water in both the well-fed and normal fasting states (only changes in prolonged fasting)
RED BLOOD CELLS can only use glucose anaerobically for all their energy needs, regardless of the individual’s metabolic state
what 5 hormones oppose the actions of insulin? what and why are these hormones called?
- glucagon
- cortisol
- epinephrine
- norepinephrine
- growth hormone
called: counterregulatory hormones because of their effects on skeletal muscle, adipose tissue, and the liver which are opposite to the actions of insulin
what happens after several weeks of fasting? (3)
- the brain derives approx. 2/3 of its energy from ketones and 1/3 from glucose
- the shift from glucose to ketones as the main 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 to no mitochondria like red blood cells continue to be dependent on glucose for their energy
in a broad stroke: how is metabolism regulated best?
through hormonal means
func in metabolism:
water-soluble peptide hormones
vs.
fat-soluble amino acid-derivative hormones and steroid hormones
water-soluble peptide hormones (like insulin) able to rapidly adjust the metabolic processes of cells via second messenger cascades
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
how are hormone levels regulated? (2)
- by feedback loops with other endocrine structures (such as the hypothalamic-pituitary axis)
- by the biomolecule upon which they act (i.e. insulin causes a decrease in blood glucose, which removes the trigger for continued insulin release)
defn: insulin
a peptide hormone secreted by the beta-cells of the pancreatic islets of Langerhans
func: insulin
a key player in the uptake and storage of glucose
by what and how is glucose absorbed?
by peripheral tissues via facilitated transport mechanisms that utilize glucose transporters located in the cell membrane
what 2 tissues require insulin for effective glucose uptake?
- adipose tissue
- resting skeletal muscle
what are the 5 tissues in which glucose uptake is not affected by insulin?
what is a difference in these types of tissues?
- nervous tissue
- kidney tubules
- intestinal mucosa
- red blood cells
- beta-cells of the pancreas
difference:
some tissues that require insulin actively store glucose when it is present in high concentrations, while other tissues that do not require insulin must still be able to absorb glucose even when the glucose concentration is low
how does insulin affect the metabolism of carbohydrates? (4)
- increases glucose uptake, 2. carbohydrate metabolism in muscle and fat and 3. glycogen synthesis in the liver
- decreases the activity of enzymes that promote glycogen breakdown
func (2): increase glucose in muscle
- used as additional fuel to burn during exercise
- can be stored as glycogen
how does insulin affect amino acid uptake by muscle cells?
it increases amino acid uptake by muscle cells, thereby increasing levels of protein synthesis and decreasing breakdown of essential proteins
how does insulin affect metabolism of fats? sum + 5 specifics
sum: significant impact especially in the liver and adipocytes
insulin increases:
1. glucose and triacylglycerol uptake by fat cells
2. lipoprotein lipase activity, which clears VLDL and chylomicrons from the blood
3. triacylglycerol synthesis (lipogenesis) in adipose tissue and the liver from acetyl-CoA
insulin decreases:
1. triacylglycerol breakdown (lipolysis) in adipose tissue
2. formation of ketone bodies by the liver
what is the most important controller of insulin secretion?
plasma glucose
above what threshold is insulin secretion directly proportional to plasma glucose?
100 mg/dL OR about 5.6 mM glucose
what must happen for glucose to promote insulin secretion?
glucose must not only enter the beta-cell but also can be metabolized, increasing intracellular ATP concentration
what impact does increased ATP have on insulin?
increased ATP –> calcium release in the cell –> promotes exocytosis of preformed insulin from intracellular vesicles
what else is insulin secretion affected by?
signaling initiated by other hormones, such as glucagon and somatostatin
do patients with type 1 diabetes synthesize insulin or glucagon? what impact does this have?
they CANNOT make insulin, but DO make glucagon
this increases blood sugar much more than if an individual were to lose all pancreatic function or to develop insulin insensitivity
defn: glucagon
a peptide hormone secreted by the alpha-cells of the pancreatic islets of Langerhans
what is the primary target for glucagon action?
the hepatocyte
what 5 affects does glucagon have as it acts through second messengers?
increased liver:
1. glycogenolysis
- gluconeogenesis
3.ketogenesis
- lipolysis
decrease: lipogenesis
what are the most important physiological promoter and inhibitor of glucagon secretion?
PROMOTER = low plasma glucose (hypoglycemia)
INHIBITOR = elevated plasma glucose (hyperglycermia)
do amino acids promote or inhibit the secretion of glucagon? which ones?
PROMOTE
especially basic amino acids (arginine, lysine, histidine)
THUS, glucagon is secreted in response to the ingestion of a meal rich in proteins
functional relationship: insulin and glucagon
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 and enzymes that are phosphorylated by insulin are generally dephosphorylated by glucagon
func + where/when do they come from: glucocorticoids
from the adrenal cortex
secreted with many forms of stress
responsible for part of the stress response
why must glucose be rapidly mobilized from the liver? (2)
- in order to fuel actively contracting muscle cells while fatty acids are released from adipocytes
- in order to make a getaway in the “fight-or-flight” response
defn: cortisol
a steroid hormone that promotes the mobilization of energy stores through the degradation and increased delivery of amino acids and increased lipolysis
how does cortisol elevate blood glucose levels? what is the impact of this?
increases glucose availability for nervous tissue through two mechanisms
- cortisol inhibits glucose uptake in most tissues (muscle, lymphoid, and fat) and increases hepatic output of glucose via gluconeogenesis, particularly from amino acids
- cortisol has a permissive function that enhances the activity of glucagon, epinephrine, and other catecholamines
impact of long-term exposure to glucocorticoids
causes persistent hyperglycemia, which stimulates insulin
this promotes fat storage in the adipose tissue, rather than lipolysis
difference in what is produces by the adrenal cortex vs. the adrenal medulla
ADRENAL CORTEX produces steroid hormones (glucocorticoids, mineralocorticoids, and sex hormones)
ADRENAL MEDULLA produces catecholamines
what secretes catecholamines? what 2 things are included in this group + their akas + diagram
secreted by the adrenal medulla
- epinephrine (aka adrenaline)
- norepinephrine (aka noradrenaline)
func (3): 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
- act on adipose tissue to increase lipolysis by increasing the activity of hormone-sensitive lipase
func: epinephrine
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 adrenal rush
4 symptoms of hypothyroidism (insufficient thyroid hormone)
- cold intolerance
- fatigue
- weight gain
- depression
metabolism suffers
4 symptoms of hyperthyroidism (excessive thyroid hormone levels)
- rapid weight loss
- anxiety
- jitteriness
- fever
what does it mean that thyroid activity is largely permissive?
thyroid hormone levels are kept more or less constant, rather than undulating with changes in metabolic state
func (3) + char (2): thyroid hormones
func: 1. increase the basal metabolic rate
2. accelerate cholesterol clearance from the plasma
3. increase the rate of glucose absorption from the small intestine
char: 1. increase in BMR is evidenced by increased O2 consumption and heat production when they are secreted
2. have primary effects in lipid and carbohydrate metabolism
difference in increase in metabolic rate produced by thyroxine (T4) and triiodothryonine (T3)
T4: increase in metabolic rate occurs after a latency of several hours but may last for several days
T3: produces a more rapid increase in metabolic rate and has a shorter duration of activity
what do the subscript numbers in T3 and T4 indicate?
the number of iodine atoms in the hormone
relationship between T4 and T3
T4 can be thought of as the precursor to T3
defn + func: deiodonases
enzymes that remove iodine from a molecule
located in target tissues and convert T4 to T3
what does epinephrine require of thyroid hormones?
to have a significant metabolic effect
what are the 4 major sites of metabolic activity in the body?
- the liver
- skeletal and cardiac muscles
- brain
- adipocytes
what type of cells are the primary secretory cells?
epithelial cells
what role do epithelial cells have with metabolism?
they are involved in the regulation of metabolism because they are the primary excretory cells, but they do not make major contributions to the consumption of energy
what are the 2 major roles of the liver in fuel metabolism?
- maintain a constant level of blood glucose under a wide range of conditions
- synthesize ketones when excess fatty acids are being oxidized
how does the liver act in the well-fed state?
between meals and during prolonged fasts?
WELL-FED: the liver derives most of its energy from the oxidation of excess amino acids
BETWEEN MEALS/PROLONGED FASTS : liver releases glucose into the blood; the increase in glucagon promotes both glycogen degradation and gluconeogenesis
what 3 things provide carbon skeletons for glucose synthesis?
- lactate from anaerobic metabolism
- glycerol from triacylglycerols
- amino acids
what 2 places does insulin trigger fatty acid release from?
- VLDL
- chylomicrons
where does the glycerol phosphate required for triacylglycerol synthesis come from?
glucose that is metabolized in adipocytes as an alternative product of glycolysis
what happens to fatty acids during the fasting state? why?
fatty acids are released into circulation
why? decreased levels of insulin and increase epinephrine activate hormone-sensitive lipase in fat cells
what are the 2 major fuels of skeletal muscle? 2 minor?
- glucose
- fatty acids
minor:
1. excess glucose
2. amino acids
why is skeletal muscle the body’s major consumer of fuel?
because of its enormous bulk
what does insulin do to skeletal muscle after a meal?
insulin promotes glucose uptake in skeletal muscle, which replenishes glycogen stores and amino acids used for protein synthesis
what happens to resting muscle 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)
what does the primary fuel used to support muscle contraction depend on?
the magnitude and duration of exercise as well as the major fibers involved
func: creatine phosphate
transfers a phosphate group to ADP to form ATP
provides a very short-lived source of energy (2-7 seconds)
what 2 things does skeletal muscle have stores of?
what 2 things may also be used?
- glycogen
- some triacylglcyerols
secondary:
1. blood glucose
2. free fatty acids
how are short bursts of high-intensity exercise supported?
by anaerobic glycolysis drawing on stored muscle glycogen
how is moderately high-intensity, continuous exercise supported? + what happens after 1-3 hours of this
oxidation of glucose and fatty acids are important, but after 1-3 hours of exercise at this level, muscle glycogen stores becomes depleted and the intensity of exercise declines to a rate that can be supported by oxidation of fatty acids
what do cardiac myocytes use for fuel?
they love fatty acids! even in the well-fed state
(or ketones if they are present during prolonged fasting)
what other type of muscle do cardiac myocytes most closely parallel in terms of energy usage?
skeletal muscle during extended periods of exercise
what happens in a failing heart? (2)
- glucose oxidation increases
- beta-oxidation falls
what is the brain’s primary fuel?
glucose
why are blood glucose levels tightly regulated?
to maintain a sufficient glucose supply for the brain
what does normal brain function depend on?
a continuous glucose supply from the bloodstream
what happens to the brain during hypoglycemic conditions (<70 mg/dL)?
hypothalamic centers in the brain sense a fall in blood glucose level and the release of glucagon and epinephrine is triggered
why are fatty acids not used as an energy source by the brain?
they cannot cross the blood-brain barrier
what does the brain use for energy between meals?
the brain relies on blood glucose supplied by either hepatic glycogenolysis or gluconeogenesis
what does the brain use for energy during prolonged fasting?
the brain gains the capacity to use ketone bodies for energy, and even then still, the ketone bodies supply 2/3 of the fuel, but the rest is still glucose
levels of what 6 things can be measured in the blood of humans to analyze metabolic control?
why can these all be used as indicators of metabolic function?
- glucose
- thyroid hormones and thryoid-stimulating hormone
- insulin
- glucagon
- oxygen
- carbon dioxide
because they have a predictable effect on metabolism
func: respirometry
allows accurate measurement of the respiratory quotient
what does the respiratory quotient differ depending on?
the fuels being used by the organism
eqn + how is it determined: respiratory quotient (RQ)
measured experimentally
for the complete combustion of a given fuel source
value: respiratory quotient for
carbs
lipids
resting individuals
carb: 1.0
lipids: 0.7
resting: 0.8 (indicates that both fat and glucose are consumed)
what 3 conditions change the respiratory quotient?
- high stress
- starvation
- exercise
func: calorimeter
can measure basal metabolic rate (BMR) based on heat exchange with the environment
what 4 things can BMR be estimated by?
- age
- weight
- height
- sex
what 4 things contribute to body mass? what 1 thing doesnt?
does:
1. water
2. carbs
3. proteins
4. fats
doesn’t:
1. nucleic acids
how do carbs, protein, water, and lipids change in the body mass/composition?
overall mass of carbs and proteins tend to be stable over time (modified slightly by starvation or muscle-building)
WATER –> very quickly adjusted by the endocrine system and the kidneys (so does not factor into obesity and weight regulation), however it is the primary source of frequent minor weight fluctuations
LIPIDS (stored in adipocytes) –> the primary factor in the gradual change of body mass over time
defn: basal metabolic rate
the amount of energy required for one sedentary day
how does BMR change as individuals increase in mass? what impact does this have on body mass?
the BMR increases
a caloric excess will cause an increase in body mass until equilibrium is reached between the basal metabolic rate and the existing intake
true or false: larger changes must be made to lose weight than to gain it
true
what are 5 factors that all have key roles in weight control?
- diet (energy intake)
- exercise (energy expenditure)
- genetics
- socioeconomic status
- geography
what 5 hormones are critical to the integration of metabolism?
- thyroid hormones
- cortisol
- epinephrine
- glucagon
- insulin
what 3 hormones control hunger and satiety?
- ghrelin
- orexin
- leptin
what causes it to come out + func: ghrelin
secreted by the stomach in response to signals of an impending meal
sight, sound, taste, and smell all act as signals for its release
increases appetite and stimulates secretion of orexin
func: orexin
further increases appetite and is also involved in alertness and the sleep-wake cycle
hypoglycemia is a trigger for its release
defn: leptin
a hormone secreted by fat cells that decreases appetite by suppressing orexin production
genetic variations in which hormone: ghrelin, orexin, or leptin; and its receptors have been implicated in obesity? + diagram of mouse
a knockout mouse unable to produce leptin
equation: body mass index (BMI)
mass (kg)
height (m)
values: normal, underweight, overweight, obese BMIs
underweight: <25
normal: 18.5-25
overweight: 25-30
obese: >30
