Homeostasis

Homeostasis plays a pervasive role in shaping the form and function of all biological molecules and organisms

Students should be able to explain and apply core concepts of underlying homeostasis, including the need for biological balance, linked steady state processes, quantification of homeostasis, the organization of chemical processes, and control mechanisms.

The learning goals below are categorized as introductory A, intermediate B and upper C.

1. Biological need for homeostasis

Biological homeostasis is the ability to maintain relative stability and function as changes occur in the internal or external environment. Organisms are viable under a relatively narrow set of conditions. As such, there is a need to tightly regulate the concentrations of metabolites and small molecules at the cellular level to ensure survival. To optimize resource use and to maintain conditions, the organism may sacrifice efficiency for robustness. Breakdown of homeostatic regulation can contribute to the cause or progression of disease or lead to cell death.

Associated learning goals

• Students should be able to describe why maintenance of homeostasis is advantageous to an organism. A
• Students should be able to define homeostasis in a biochemical context to both scientifically trained and lay audiences. B
• Students should be able to describe how homeostatic pathways and mechanisms have been conserved throughout evolution. B
• Students should be able to appraise the costs and benefits of different homeostatic mechanisms to an organism. C
• Students should be able to relate different environmental factors necessitating homeostasis to a specific adaptation. C

2. Link steady state processes and homeostasis

A system that is in a steady state remains constant over time, but that constant state requires continual work. A system in a steady state has a higher level of energy than its surroundings. Biochemical systems maintain homeostasis via regulation of gene expression, metabolic flux and energy transformation but are never at equilibrium.

Associated learning goals

• Students should be able to explain that a system at chemical equilibrium (or just equilibrium) is stable over time, but no energy or work is required to maintain that condition. A
• Students should be able to apply the principles of kinetics to describe flux through biochemical pathways. A
• Students should be able to discuss a metabolic pathway in terms of equilibrium and Le Chatelier’s principle. A
• Students should be able to relate the laws of thermodynamics to homeostasis and explain how the cell or organism maintains homeostasis. B
• Students should be able to model how perturbations to the steady state can result in changes to the homeostatic state. C
• Students should be able to propose how resources stored in the homeostatic state can be utilized in times of need. C

3. Quantifying homeostasis

Multiple reactions with intricate networks of activators and inhibitors are involved in biological homeostasis. Modifications of such networks can lead to activation of previously latent metabolic pathways or even to unpredicted interactions between components of these networks. These pathways and networks can be mathematically modeled and correlated with metabolomics data and kinetic and thermodynamic parameters of individual components to quantify the effects of changing conditions related to either normal or disease states.

Associated learning goals

• Students should be able to describe experiments discussing how signaling and regulatory molecules and metabolic intermediates can be quantitated in the laboratory. A
• Students should be able to relate concentrations of key metabolites to steps of metabolic pathways and describe the roles they play in homeostasis. A
• Students should be able to calculate enzymatic rates and compare these rates and relate these rates back to cellular or organismal homeostasis. B
• Students should explain that organismal homeostasis can be measured in multiple ways and over different time scales (seconds, minutes, hours, days and months). B
• Students, given a metabolic network and appropriate data, should be able to predict the outcomes of changes in parameters of the system such as increased concentrations of certain intermediates or the changes in the activity of certain enzymes. C

4. Control mechanisms

Homeostasis is maintained by a series of control mechanisms functioning at the organ, tissue or cellular level. These control mechanisms include substrate supply, activation or inhibition of individual enzymes and receptors, synthesis and degradation of enzymes, and compartmentalization. The primary components responsible for the maintenance of homeostasis can be categorized as stimulus, receptor, control center, effector and feedback mechanism.

Associated learning goals

• Students should be able to discuss how chemical processes are compartmentalized in the organism, organ and the cell. A
• Students should be able to explain why biochemical pathways proceed through the intermediates that they do (gradual oxidation or reduction) and why pathways share intermediates. A
• Students should be able to summarize the different levels of control (including reaction compartmentalization, gene expression, covalent modification of key enzymes, allosteric regulation of key enzymes, substrate availability and proteolytic cleavage) and relate these different levels of control to homeostasis. A
• Students should be able to compare the temporal aspect of different control mechanisms (e.g. how quickly phosphorylation occurs versus changes in gene expression). A
• Students should be able to hypothesize why and how organs evolved with specialized function in metazoans. B
• Students should be able to discuss different models of allosteric regulation. B
• Students should be able to formulate models relating changes in flux through a pathway to other pathways and overall homeostasis. C
• Students should be able to defend why anabolic and catabolic pathways are compartmentalized in the cell. C

5. Cellular and organismal homeostasis

Homeostasis in an organism or colony of single celled organisms is regulated by secreted proteins and small molecules often functioning as signals. Homeostasis in the cell is maintained by regulation and by the exchange of materials and energy with its surroundings.

Associated learning goals

• Students should be able to describe how the cell and organism store resources (both in terms of stored energy and chemical building blocks) for times of need and how they mobilize these resources. A
• Students should be able to integrate homeostasis from the cellular to the organismal level. In other words, students should be able to describe how a complex metazoan can have both a cellular and organismal response to maintain homeostasis. B
• Students should be able to compare and contrast homeostasis in different organisms. B
• Students should be able to describe homeostasis at the level of the cell, organism or system of organisms and hypothesize how the system would react to deviations from homeostasis. C