Chapter 1
Biological Structure and Function

1. 1.1 Cell Energy Related to Whole-Body Function
2. 1.2 Tissue and Organ Systems
3. 1.3 Cell Structure and Energy Metabolism

Living organisms operate much like a complicated chemical factory in which raw materials from the surrounding environment are distributed to chemical reactors that produce desired products along with waste that must be discarded back to the environment. And just like a chemical factory, a living organism must be capable of purifying raw materials and separating desired products from wastes. In humans, nutrients are separated from food in the upper gastrointestinal tract, oxygen is separated from air in the lungs, and many of the critical reactions that utilize these raw materials occur in the liver. Waste products are eliminated through the lower gastrointestinal tract and the kidneys as well as the lungs. It is the collection of all these chemical processes that enable an organism to maintain itself, perform work, grow, and reproduce.

The human body consists of about 100 trillion cells, each bathed in its own fluid microenvironment. In an adult, there is about 40?L of fluid, a third of which are extracellular (located outside of cells) and two-thirds of which are intracellular (located within cells). Various chemical species are nonuniformly distributed between the extracellular and intracellular fluids (Fig. 1.0-1), and there is a constant movement of ions, nutrients, waste products, and other substances between these fluid compartments. A function required of all cells is the regulation of these dynamics such that the chemical and energy needs of an organism are met.

Figure 1.0-1 Homeostatic concentration conditions.

Nature has provided for this by enclosing cells in a specialized membrane that supports a variety of transport processes, some of which are passive and others that are active in nature. During passive diffusion, the movement of a substance across a membrane occurs spontaneously in the direction of decreasing chemical potential. The uptake of O2 from a relatively high concentration in extracellular fluid to a lower concentration in intracellular fluid is an example of passive diffusion. During active transport, energy from an independent chemical source is harnessed, allowing a substance to cross a membrane in the direction of increasing chemical potential. The maintenance of a low intracellular sodium level, for example, requires active transport of sodium out of cells to compensate for the passive leakage of sodium into cells.

Several energy-requiring processes in addition to active transport are necessary if an organism is to function properly and maintain its structural integrity. Energy is consumed by many of the metabolic reactions that synthesize essential molecules within cells. Energy is needed for muscular contraction in the heart, lungs, and limbs. Also, energy dissipation as heat is necessary to maintain a normal body temperature of about 37°C. The ultimate source of energy for all these tasks is the controlled oxidation of nutrients. In the remainder of this chapter, we will discuss how metabolic reactions and chemical transport are coordinated at different levels of structural organization, beginning at the whole-body level, progressing to the organ level, and ending at the cellular level.

1.1 Cell Energy Related to Whole-Body Function

Food entering the mouth is degraded to simpler molecules by hydrolytic reactions that occur in the oral cavity and the stomach. Additional chemical reactions occur downstream in the small intestine where the digested nutrients are absorbed into the bloodstream, ultimately reaching the intracellular space where they are oxidized to liberate energy. Humans eat foods containing a variety of different carbohydrates, fats, and proteins. However, the chemical selectivity of transport and reaction processes in the gastrointestinal tract produces a limited number of digestive products, such as glucose, fructose, and galactose, resulting from carbohydrate breakdown; triglycerides from fat breakdown; and amino acids from protein breakdown. Most of the galactose and fructose absorbed by the intestines are rapidly converted to glucose in the liver. Thus, glucose, triglycerides, and amino acids are the principal substrates for energy metabolism and chemical synthesis in the body.

During resting conditions, the minimal power requirement of an adult is about 70?W. This rate of energy production is provided primarily by the complete oxidation of glucose and triglycerides into CO2 and water. These combustion reactions require about 250?ml/min of O2 uptake through the respiratory tract. Even when a person's energy requirement is greater than 70?W, a suitable O2 supply is usually available to sustain this aerobic metabolism. When a person is involved in very strenuous exercise, however, the energy demand can be so great that glucose is incompletely oxidized, forming a waste product, lactic acid, by anaerobic metabolism. Whether energy metabolism is aerobic or anaerobic, amino acids can never be completely oxidized. Rather, they are partially oxidized and form nitrogenous waste products, urea and creatinine, that are excreted by the kidneys.

1.1.1 Energy Generation

Suppose we burn a nutrient with O2 in a closed vessel at an initial temperature of 37°C and we measure the heat that must be removed to reach a final temperature of 37°C. According to thermodynamics, the heat extracted from this calorimeter is identical to the total energy extracted as heat and work when the same reaction is carried out in a person at a constant body temperature of 37°C. Thus, the thermal information obtained from an inanimate calorimeter experiment is directly applicable to energy metabolism in a living organism, even though the mechanisms of nutrient oxidation are quite different.

The complete combustion of glucose with a stoichiometric amount of O2 carried out in a calorimeter at atmospheric pressure and body temperature conditions yields the following information about carbohydrate metabolism:

The respiratory quotient (RQ), defined as the molar output of CO2 relative to the molar input of O2 (equivalent to the CO2 production volume relative to the O2 consumption volume), is a direct result of the reaction stoichiometry. The heat of combustion ?Hr is defined as heat that must be added per gram of glucose that is consumed. Because heat must actually be removed from a calorimeter to maintain a fixed pressure and temperature, ?Hr is a negative quantity. The calorific equivalent (CE) represents the value of relative to the volume of O2 consumed. Therefore, the combustion of 1?g of glucose produces 15.6?kJ of energy, burns 15.6/21.0?=?0.743?L of O2, and produces 0.743(1.00)?=?0.743?L of CO2.

Although many triglycerides participate in energy metabolism, we can model these reactions by focusing on a single triglyceride with a relative number of carbon-hydrogen-oxygen atoms similar to most other triglycerides. Calorimetric measurements of the complete combustion of triolein (C57H104O6), one such model of triglyceride, result in the following data:

We see from these values that 1?g of triolein produces 16.0?kJ of energy, burns 16.0/18.5?=?0.865?L of O2, and produces 0.865(0.713)?=?0.617?L of CO2. Thus, on a per gram basis, fat metabolism produces slightly more energy, requires substantially more O2, and produces significantly less CO2 than carbohydrate metabolism.

Because of diversity in the structure of amino acids, we cannot model their energy metabolism with a specific compound. However, calorimetric measurements of a typical mix of foodstuffs have established representative parameter values for the oxidation of ingested proteins: RQ?=?0.81, , and CE?=?19.2?kJ/L O2. Although these values indicate that proteins are a favorable energy source, the amino acids created during protein digestion are normally more important for synthesizing new proteins than for producing energy.

Indirect calorimetry is a convenient procedure for evaluating energy metabolism from the rates at which a person excretes CO2 to and extracts O2 from the surroundings. The RQ associated with this CO2-O2 exchange can identify the types of nutrients being metabolized. Values of CE can then be used to predict energy production, and nutrient consumption rate can be estimated from ?Hr. Consider the example of a person who consumes 300?ml/min of O2 and excretes CO2 at 300?ml/min as determined from respired gas measurements. With RQ?=?300/300?=?1, it is likely that carbohydrates are the primary substrates being consumed. It follows that energy is produced at (21,000?J/L)(0.300?L/min)?=?6300?J/min and the person metabolizes carbohydrates at a rate of (6300?J/min)(1440?min/day)/(15,600?J/g)?=?582?g/day?~?1?lb/day.

1.1.2 Energy Transfer

By virtue of their high-energy phosphate groups, several nucleotides act as intermediates between the chemical reactions that generate energy and those that utilize energy. The most abundant of these nucleotides is adenosine triphosphate (ATP). At the fairly neutral pH conditions in physiological systems, ATP has a valence of...