MCAT Biochemistry Review

Chapter 12: Bioenergetics and Regulation of Metabolism

12.7 Integrative Metabolism

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.

MCAT EXPERTISE

The MCAT does not expect you to know what levels are healthy for any of these indicators, but can easily pose data interpretation questions related to them.

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:

Equation 12.3

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 action of different hormones.

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.

REGULATION OF BODY MASS

Until now, we've been discussing metabolism on a very small scale, but metabolic controls are also involved in maintaining body mass (weight loss or gain). Body mass is primarily determined by several factors, including water, carbohydrates, proteins, and lipids, while nucleic acids do not contribute significantly to its maintenance. The overall mass of carbohydrates and proteins tends to be stable over time, although it can be modified slightly by periods of prolonged starvation or by significant muscle-building activities. Water is very quickly adjusted by the endocrine system and the kidneys; therefore, it does not factor into our discussion of obesity and weight regulation. Water is the primary source of frequent minor weight fluctuations because it is subject to rapid adjustment. Therefore, lipids, stored in adipocytes, are the primary factor in the gradual change of body mass over time.

An individual who is maintaining his weight consumes the same amount of energy that is spent on average each day. If energy consumed is greater than energy expenditure over a significant period of time, then fat stores begin to accumulate. The opposite is also seen. If an energy deficit exists where calories consumed are less than calories burned, then a decrease in weight is observed. As individuals increase in mass, basal metabolic rate (the amount of energy required for one sedentary day) also increases. Thus, a caloric excess will cause an increase in body mass until equilibrium is reached between the new basal metabolic rate and the existing intake. In weight loss the reverse trend is seen.

This effect does have a threshold that differs between individuals. Small adjustments in intake, even over a prolonged period of time, are partially or fully compensated by changes in energy expenditure. Similarly, a small increase or decrease in activity level will be compensated by changes in hunger. Deliberate alterations of body mass require alterations above this threshold level, which is higher in negative energy balance than in positive energy balance—in other words, larger changes must be made to lose weight than to gain it.

Diet (energy intake) and exercise (energy expenditure), genetics, socioeconomic status, and geography all play key roles in weight control. As described earlier, hormonal control by thyroid hormones, cortisol, epinephrine, glucagon, and insulin is critical to the integration of metabolism. In addition, there are hormones that control hunger and satiety, including ghrelinorexin, and leptin. Have you ever wondered why, even if you don't feel hungry, when you walk into your favorite restaurant you're suddenly ravenous? This is the job of ghrelin and orexin. 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. Orexin further increases appetite, and is involved in alertness and the sleep–wake cycle. Hypoglycemia is also a trigger for orexin release. 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; a knockout mouse unable to produce leptin is shown on the left in Figure 12.11. These messengers and receptors are the target of current research; for now, questions regarding body mass modifications on the MCAT mostly come down to food and exercise.

Figure 12.11. Leptin Knockout Mouse (left) Compared to Normal Mouse (right)

BRIDGE

Motivation, a psychological concept discussed in Chapter 5 of MCAT Behavioral Sciences Review, is often linked with physiological drives and signaling pathways. The hypothalamus, which produces orexin and responds to leptin and ghrelin, is responsible for regulating hunger, thirst, and libido.

MCAT Concept Check 12.7:

Before you move on, assess your understanding of the material with these questions.

1.    How is the respiratory quotient expected to change when a person transitions from resting to brief exercise?

2.    True or False: Body mass can be predicted by the leptin receptor phenotype and caloric intake alone.

3.    True or False: It is easier to gain weight than to lose weight.

4.    If you were designing a study to assess metabolism, which measurement method would you choose? Defend your answer.