ENERGY METABOLISM All reactions involve a change in energy. 1st Law of Thermodynamics Energy is neither created nor destroyed 2nd Law of Thermodynamics No energy conversion is 100% efficient. There is always an increase in disorder (i.e. ENTROPY, S) of the system. Heat-emitting reactions are EXOTHERMIC (or EXERGONIC). Synthetic reactions require the input of heat and are thus ENDOTHERMIC (ENDERGONIC). The ENTHALPY (H) is the heat content of the system. We are primarily concerned with the change in free energy (G) associated with a reaction. This involves both a change in H and a change in S. Delta G = delta H - T delta S, where T = absolute temperature. Many biological reactions involve OXIDATIONS (exothermic) and REDUCTIONS (Endothermic). Oxidation = removal of electrons (often accompanied by addition of oxygen and/or removal of hydrogen. Reduction = addition of electrons (often accompanied by removal of oxygen and/or addition of hydrogen. These tend to be coupled reactions: AH2 + B –> A + BH2 A is oxidized and B is reduced. Example: C6H12O6 + 6O2 –> 6CO2 + 6H2O Complete oxidation of glucose = -673 kcal/mole Typical increase in entropy = 13 kcal/mole Therefore, delta G = -673 -13 = -686 kcal/mole Although the reaction is exothermic, glucose will not oxidize spontaneously. An ACTIVATION ENERGY barrier must be overcome before the reaction will proceed. [see Figure] ENZYMES are organic catalysts, which lower the activation energy barrier and greatly accelerate a reaction. The enzyme itself is not consumed in the reaction. S + E <–> ES complex –> E + P S = substrate, E = enzyme, P = product [Fig. 3-33] Alternative models for enzyme action: The first model suggests that the substrate(s) fit the binding site like a key in a lock. The second model suggests that attachment of the substrate(s) induces a shape change in the enzyme, which triggers a binding reaction. [see Animation] Reaction velocity varies with substrate concentration: [see Figure] Km if the Michaelis Constant. 1/Km is a measure of the affinity of an enzyme for the substrate. Reactions are also influenced by factors such as pH, temperature, and inhibitors. [see Figures] Biological oxidations are step-wise processes. This allows free energy to be "trapped" (e.g. converted to ATP) at various steps in the pathway. Pathways are linked with other pathways to form complex networks ("webs"). The "flow" can thus be shifted from one pathway to another depending upon the activities of the enzymes that control each step. Metabolic reactions are affected by: [Fig. 3-41] [see Figure] Glycolysis [Fig. 3-42] [see Figure] Glycolysis provides a net yield of 2 molecules of ATP per glucose molecule. Free energy of ATP is approx. 7 kcal/mole. [see Figure] Kreb's Cycle Two CO2 molecules are produced per turn of the cycle. Although only one "ATP" is directly produced, many more can be formed via OXIDATIVE PHOSPHORYLATION in the mitochondria. [see Figure] Oxidative Phosphorylation One molecule of reduced NAD can be oxidized (i.e. "cashed in") to produce 3 ATP molecules. One reduced FAD will yield 2 ATP molecules. [Fig. 3-45] [see Animation] [see Figure] C6H12O6 –> 6 CO2 + 6 H2O The complete oxidation of glucose yields 36 ATPs Glucose –> 2 Pyruvate 2 ATP 2 NADH2 –> 2 FADH2 –> 4 ATP 2 Pyruvate –> 6 CO2 8 NADH2 –> 24 ATP 2 FADH2 –> 4 ATP 2 GTP –> 2 ATP TOTAL = 36 ATP [Fig. 3-40] CATABOLIC EFFICIENCY: Glucose –> lactate: Delta G = 47 kcal 2 ATP = 14 kcal Efficiency = 30% Glucose –> carbon dioxide and water Delta G = 686 kcal 36 ATP = 252 kcal Efficiency = 37% LIPID METABOLISM: Recall that neutral fat (triacylglycerol) consists of three fatty acids attached to glycerol (3C). The first step in the catabolism of neutral fat is to remove the fatty acids from the glycerol. Glycerol plugs directly into the glycolytic pathway. Fatty acids are oxidized two carbons at a time (beta oxidation) forming acetyl CoA, which plugs into the Kreb's Cycle. [Fig. 3-49] PROTEIN METABOLISM: Proteins are catabolized first to peptides (chains of amino acids) and then to amino acids. The amino group (NH2) is removed via deamination or transamination and the resulting organic acid is processed via the Kreb's Cycle. Mammals and some other animals convert ammonia (NH3) to urea via a second metabolic cycle. [Fig. 3-51] [see Figure] Urea Synthesis [see Figure] OVERVIEW OF CELLULAR METABOLISM [Fig. 3-53] ENERGY BALANCE The kilocalorie (kcal or Calorie or Cal) is the usual energy unit used by physiologists. This is the amount of heat needed to raise 1 kg of water from 15 to 16 C. Different foodstuffs have different caloric values: Carbohydrate = 4.1 Cal/g Lipid = 9.3 Cal/g Protein = 5.6 (4.1) Cal/g NOTE: 4.1 is the physiological heat value for protein When in balance: Energy intake = Energy expenditure Excess energy is primarily stored as body fat. The control centers for energy balance are in the HYPOTHALAMUS. The hormone LEPTIN, which is produced by adipose tissue, is the key (but not the only) element of the homeostatic system to maintain energy balance. Leptin decreases the drive to eat, and increased body fat is associated with inceased levels of leptin. Contemporary American society is obsessed with dieting and with associated real or imagined health problems. OBESITY is a genuine health concern. The health risk from obesity appears to be greater for men than for women – probably because men are prone to accumulate abdominal fat (more dangerous because more prone to enter circulating blood) as opposed to hip or thigh fat. [see Figure] Hunger is a strong and basic drive, and the greater the weight loss, the greater the hunger. Thus, regardless of motivation, dieting is generally ineffective in achieving substantial weight loss over the long run. Obesity is NOT a personal failing The body mass index (BMI) = the weight (in kg) divided by the square of the height (in m). BMI > 25 = overweight BMI > 30 = obese Facts about obesity:
1. Because obesity is defined as a threshold (BMI > 30), a small increase in average weight will lead to a disproportionate increase in obesity. i.e. The average BMI in the USA increased from 26.7 in 1991 to 28.1 in 2000, reflecting an average weight increase between 7 and 10 pounds. However, the incidence of obesity increased by 1/3 (from 23.3 to 30.9%). Facts about obesity:
2. The drive to eat is mostly hardwired, and differences in weight are generically determined with a heritability about equivalent to that for height. The great majority of obese individuals are leptin resistant. Facts about obesity:
3. Obesity was selected for in populations where food was only sporadically available and where the risk of famine was ever present (e.g. in hunter-gatherer societies). However, obesity was and is selected against in agricultural societies with the ability to store food (e.g. in "Fertile Crescent" or "Western" societies). Descendents of the former societies tend to be much more leptin resistant than are those of the latter groups. Does it matter WHAT one eats? No (a Calorie is a Calorie is a Calorie) and Yes (the cost of converting excess intake to stored fat varies with food type) [see Figure] OBESITY is a genuine health concern. However, there are enormous societal pressures (especially for young women) to conform to a certain body shape or weight. EATING ORDERS (such as ANOREXIA NERVOSA and BULIMIA) have reached epidemic proportions in certain segments of our society. CALORIMETRY is used to measure energy metabolism. We usually use indirect calorimetry (e.g. measure O2 consumption). BASAL METABOLIC RATE (BMR) = energy metabolism under standard resting post-absorptive conditions. This is often expressed as Cal/m^2/hr. BMRs tend to decrease with age and are typically greater for males than for females. The two major factors affecting the metabolic rate of a given organism are: When comparing the resting metabolic rates of different organisms at moderate temperatures, the two dominant factors are: [see Figures] We usually plot these data as a power function (i.e. log - log plot). Slope = 0.75 Metabolic rate is therefore proportional to body mass to the 0.75 power. THERMAL BIOLOGY Molecules are constantly moving at any temperature above absolute zero (-273 C). We experience this motion (i.e. kinetic energy) as HEAT. Temperature is a measure of the average kinetic energy of a system (i.e. a measure of heat intensity, not of heat content). Temperature is, arguably, the most important ABIOTIC factor affecting living organisms. Active animal life is restricted to quite a narrow range of body temperatures (roughly from -2 to +50 C), and no single species can operate effectively over this entire range. Most animals can not TOLERATE temperatures above +40 C, although a few have exceptional heat tolerance. Few animals can tolerate extreme subzero temperatures, though some can survive SUPERCOOLING to -10 C or lower and some can even withstand FREEZING of body tissues. There are four basic mechanisms of HEAT EXCHANGE between an animal and its environment: RADIATION CONDUCTION CONVECTION WATER VAPORIZATION The direction of heat transfer for the first three mechanisms is from hot to cold. The 4th mechanism is the only way for an animal to lose heat to a warmer environment (i.e. EVAPORATIVE COOLING). [see Figure] All living animals both produce heat metabolically and exchange heat with their environment. Tb = body temperature Ta = ambient temperature ECTOTHERMS: Tb depends primarily on Ta ENDOTHERMS: Tb depends primarily on metabolic heat HETEROTHERMS: Sometimes ectotherms, sometimes endotherms. HOMEOTHERMS: Tb is relatively constant POIKILOTHERMS: Tb varies with Ta [see Figures] Idealized Relaltionships The metabolic rate of an ectotherm (like the rate of a typical chemical reaction) tends to double or triple for each 10 C increase in temperature. Q
Q10 = (R2/R1)^10/(T2 - T1)
Where R
2 is the rate at the higher temperature (T2) and R1 the rate at T1.The metabolism - temperature curve for endotherms is more complex.
Newton's Law of Cooling:
[see Figure] Rate of cooling is proportional to (Tb - Ta)
Heat loss = C (Tb - Ta)
C = THERMAL CONDUCTANCE
C = heat loss/(Tb - Ta)
If an endotherm remains homeothermic at low temperatures via metabolic heat production, then
Heat loss = heat gain = metabolic rate
Therefore, C = metabolic rate/(Tb - Ta)
[see Figure]
Below the TNZ:
C = minimal and constant
Chemical thermoregulation
Exercise
Shivering
Non-shivering thermogenesis (NST)
Major tissue = Brown Adipose Tissue (BAT)
Within the TNZ:
C = variable
Physical thermoregulation
Peripheral vasoconstriction or dilation
Piloerection
Postural adjustments, etc.
Above the TNZ:
Behavioral adjustments
EVAPORATIVE COOLING
SWEATING
Takes little energy
Loss of electrolytes
Need to keep skin cool
PANTING
Some energy cost
Risk of RESPIRATORY ALKALOSIS
Passive heat loss from hot skin
[Fig. 16-18]