MCAT Biochemistry Review

Chapter 12: Bioenergetics and Regulation of Metabolism

Conclusion

In this chapter, we reviewed the principles of thermodynamics and thermochemistry that were introduced in general chemistry and physics and their applications to biological systems. We looked at the specific energy molecules of human metabolism, the sources of energy, and key reaction types in ATP synthesis and hydrolysis. We compared different energy states and their impact on overall metabolism and tissue-specific metabolism.

At this point you should have a decent idea about how to determine what energy sources are being used from experimental data, and be able to make predictions about the changes in metabolism under varying conditions. Congratulations, because this is the last chapter of MCAT Biochemistry Review and you're just about ready to tackle any of the challenges that you will face on Test Day. Continue practicing, and try not to skip lunch!

Concept Summary

Thermodynamics and Bioenergetics

·        Biological systems are considered:

o   Open, wherein matter and energy can be exchanged with the environment, or

o   Closed, wherein only energy can be exchanged with the environment.

o   This determination is made based on the examination of the entire organism or an isolated process.

·        Changes in enthalpy in a closed biological system are equal to changes in internal energy, which is equal to heat exchange within the environment.

·        No work is performed in a closed biological system because pressure and volume remain constant.

·        Entropy is a measure of energy dispersion in a system.

·        Physiological concentrations are usually much less than standard concentrations.

·        Free energy calculations must be adjusted for pH (ΔG°′), temperature (37°C = 310 K), and concentrations.

The Role of ATP

·        ATP is a mid-level energy molecule.

·        ATP contains high-energy phosphate bonds that are stabilized upon hydrolysis by resonance, ionization, and loss of charge repulsion.

·        ATP provides energy through hydrolysis and coupling to energetically unfavorable reactions.

·        ATP can also participate in phosphoryl group transfers as a phosphate donor.

Biological Oxidation and Reduction

·        Biological oxidation and reduction reactions can be broken down into component half-reactions.

·        Half-reactions provide useful information about stoichiometry and thermodynamics.

·        Many oxidation–reduction reactions involve an electron carrier to transport high-energy electrons.

·        Electron carriers may be soluble or membrane-bound.

o   Flavoproteins are one subclass of electron carriers that are derived from riboflavin (vitamin B2).

Metabolic States

·        Equilibrium is an undesirable state for most biochemical reactions because organisms need to harness free energy to survive.

·        In the postprandial/well-fed (absorptive) state, insulin secretion is high and anabolic metabolism prevails.

·        In the postabsorptive (fasting) state, insulin secretion decreases while glucagon and catecholamine secretion increases.

o   This state is observed in short-term fasting (overnight).

o   There is a transition to catabolic metabolism.

·        Prolonged fasting (starvation) dramatically increases glucagon and catecholamine secretion.

o   Most tissues rely on fatty acids.

o   At maximum,  of the brain's energy can be derived from ketone bodies.

Hormonal Regulation of Metabolism

·        Insulin and glucagon have opposing activities during most aspects of metabolism.

o   Insulin causes a decrease in blood glucose levels by increasing cellular uptake.

o   Insulin increases the rate of anabolic metabolism.

o   Insulin secretion by pancreatic β-cells is regulated by blood glucose levels.

o   Glucagon increases blood glucose levels by promoting gluconeogenesis and glycogenolysis in the liver.

o   Glucagon secretion by pancreatic α-cells is stimulated by both low glucose and high protein levels.

·        Glucocorticoids increase blood glucose in response to stress by mobilizing fat stores and inhibiting glucose uptake.

o   Glucocorticoids increase the impact of glucagon and catecholamines.

·        Catecholamines promote glycogenolysis and increase basal metabolic rate through their sympathetic nervous system activity.

·        Thyroid hormones modulate the impact of other metabolic hormones and have a direct impact on basal metabolic rate.

o   T3 is more potent than T4, but has a shorter half-life and is available in lower concentrations in the blood.

o   T4 is converted to T3 at the tissues.

Tissue-Specific Metabolism

·        The liver is the most metabolically diverse tissue.

o   Hepatocytes are responsible for the maintenance of blood glucose levels by glycogenolysis and gluconeogenesis in response to pancreatic hormone activity.

o   The liver also participates in the processing of lipids and cholesterol, bile, urea, and toxins.

·        Adipose tissue stores lipids under the influence of insulin and releases them under the influence of epinephrine.

·        Skeletal muscle metabolism differs based on the current activity level and fiber type.

o   Resting muscle conserves carbohydrates in glycogen stores and uses free fatty acids from the bloodstream.

o   Active muscle may use anaerobic metabolism, oxidative phosphorylation of glucose, direct phosphorylation from creatine phosphate, or fatty acid oxidation, depending on fiber type and exercise duration.

·        Cardiac muscle uses fatty acid oxidation in both the well-fed and fasting states.

·        The brain and other nervous tissues consume glucose in all fasting states, except for prolonged fasts, where up to  of the brain's fuel may come from ketone bodies.

Integrative Metabolism

·        Metabolic rates can be measured using calorimetryrespirometry, consumption tracking, or measurement of blood concentrations of substrates and hormones.

·        Composition of fuel that is actively consumed by the body is estimated by the respiratory quotient (RQ).

·        Body mass regulation is multifactorial with consumption and activity as modifiable factors.

o   The hormones leptinghrelin, and orexin, as well as their receptors, play a role in body mass.

o   Long-term changes in body mass result from changes in lipid storage.

o   Changes in consumption or activity must surpass a threshold to cause weight change. The threshold is lower for weight gain than for weight loss.

Answers to Concept Checks

·        12.1

1.    ΔG°′ adjusts only for the pH of the environment by fixing it at 7. Temperature and concentration of all other reagents are still fixed at their values from standard conditions and must be adjusted for if they are not 1 M.

2.    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.

3.     

 

+ΔH

−ΔH

S

Spontaneous at high temperatures

Spontaneous

−ΔS

Nonspontaneous

Spontaneous at low temperatures

·        12.2

1.    ATP hydrolysis yields about  of energy, 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.

2.    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.

3.   

·        12.3

1.    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.

2.     

Electron Carrier

Metabolic Pathway(s)

NADH

Glycolysis, fermentation, citric acid cycle, electron transport chain

NADPH

Pentose phosphate pathway, lipid biosynthesis, bleach formation, oxidative stress, photosynthesis

Ubiquinone (CoQ)

Electron transport chain

Cytochromes

Electron transport chain

Glutathione

Oxidative stress

·        12.4

1.    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.

2.    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.

3.    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.

·        12.5

1.    Insulin promotes glucose uptake by adipose tissue and muscle, glucose utilization in muscle cells, and macromolecule storage (glycogenesis, lipogenesis). Glucagon increases blood glucose levels by promoting glycogenesis, gluconeogenesis, lipolysis, and ketogenesis. Cortisol increases lipolysis and amino acid mobilization, while decreasing glucose uptake in certain tissues and enhancing the activity of other counterregulatory hormones. Catecholamines increase glycogenolysis in muscle and liver and lipolysis in adipose tissue. Thyroid hormones increase basic metabolic rate and potentiate the activity of other hormones.

2.    Thyroid storm presents with hyperthermia (high temperature), tachycardia (fast heart rate), hypertension (high blood pressure), and tachypnea (high respiratory rate).

·        12.6

1.    The preferred fuel for most cells in the well-fed state is glucose; the exception is cardiac muscle, which prefers fatty acids.

2.    The brain consumes the greatest amount of glucose relative to its percentage of body mass.

3.    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.

·        12.7

1.    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.

2.    False; energy expenditure, genetics, socioeconomic status, geography, and other hormones also play a role in body mass regulation.

3.    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.

4.    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.

Equations to Remember

(12.1) Gibbs free energy: ΔG = ΔH − TΔS

(12.2) Modified standard state: ΔG = ΔG° + RT ln (Q)

(12.3) Respiratory quotient

Shared Concepts

·  Biochemistry Chapter 9

·  Carbohydrate Metabolism I

·  Biochemistry Chapter 10

·  Carbohydrate Metabolism II

·  Biochemistry Chapter 11

·  Lipid and Amino Acid Metabolism

·  Biology Chapter 11

·  The Endocrine System

·  General Chemistry Chapter 11

·  Oxidation–Reduction Reactions

·  Physics and Math Chapter 3

·  Thermodynamics