Chapter 1-6 Review: Homeostasis, Metabolism, and Enzymes
Metabolism
Metabolism is the sum total of all the chemical reactions happening inside an organism (the human body in this transcript).
Cells produce energy in the form of ATP (adenosine triphosphate) and use that ATP to perform their specific jobs.
After energy is used, it must be replaced; metabolism is essentially cells using ATP to get their job done.
Maintaining the environment of each cell and the body as a whole requires homeostasis.
Homeostasis: dynamic equilibrium and set point
Homeostasis is defined as a dynamic state of equilibrium: a set point represents a comfortable internal environment, but the external environment is constantly changing (day/night, light/dark, temperature, wind, etc.).
The body continuously adjusts to maintain internal stability despite external fluctuations.
Homeostasis involves detecting changes (stimuli) and initiating responses to keep the internal environment within acceptable limits.
The concept of a dynamic equilibrium contrasts with a static balance; it is constantly adjusted but aims to keep conditions around a set point.
Cellular communication for homeostasis
Cells communicate mainly through two systems:
Nervous system: uses nerve impulses to rapidly relay information and elicit fast responses (e.g., regulate body temperature).
Endocrine system: uses hormones released into the blood to communicate with distant cells; slower but longer-lasting effects.
Process overview (common to both systems): stimulus → receptor detects change → control center (brain) processes information → effector organs/tactors execute a response → environment is adjusted toward set point.
Example: eating donuts increases blood glucose; endocrine signals tell cells to utilize the glucose and regenerate ATP.
Temperature regulation pathway (negative and positive feedback)
Temperature homeostasis example involves receptors sensing external temperature changes, sending information to the brain, which then signals effectors (e.g., sweat glands, skeletal muscles).
Negative feedback (thermostat-like): if temperature rises, responses lower it; if temperature falls, responses raise it.
Positive feedback is less common and amplifies the original stimulus (e.g., blood clotting).
Temperature set point and responses
Normal body temperature is about 37^ ext{o} ext{C} (Celsius).
In Fahrenheit the approximate reference is 98.6^ ext{o} ext{F} (the transcript mentions this conversion; note the common nurse reference).
If external temperature is very hot (e.g., 110^ ext{o} ext{F}), receptors trigger sweating via exocrine glands to evaporatively cool the body and return to the set point.
If external temperature is very cold (e.g., 30^ ext{o} ext{F} in winter), muscles (skeletal) generate heat via shivering to raise temperature toward the set point.
A balanced state is when internal temperature is within about ext{±}1^ ext{o} ext{C} of the set point.
Blood clotting as a positive feedback example
When a blood vessel is damaged, the body initiates a positive feedback loop to rapidly seal the leak.
Endothelial damage triggers a signal that recruits platelets to the site.
Recruited platelets release chemicals that attract more platelets, amplifying the response.
The loop continues until the damaged area is covered and bleeding stops (off switch).
Reaction rates, activation energy, and factors affecting them
Substrates (reactants) are converted into products; there is a high-energy barrier called the activation energy, (E_a), that must be overcome for the reaction to proceed.
Higher activation energy barrier ((E_a)) → slower reaction rate.
Lower activation energy barrier → faster reaction rate.
Temperature increases diffusion and collision frequency of substrates, raising the chance of productive encounters that form products.
Three main factors affecting reaction rates:
Temperature (thermal energy): higher temperatures increase molecular motion and collisions, speeding up reactions; lower temperatures slow them down.
Activation energy barrier height ((E_a)): higher barriers require more energy for the reaction to proceed, slowing the rate.
Substrate concentration: higher concentrations increase the likelihood of collisions and product formation.
In a chemical system, substrates diffusing and colliding can lead to spontaneous reactions, but in the body, enzymes provide a controlled and efficient pathway.
Enzymes: catalysts of metabolic reactions
Enzymes are proteins (made of amino acids) folded into a specific shape to perform a particular job; they act as catalysts to increase reaction rates by lowering the activation energy.
An enzyme lowers the activation energy barrier so that substrates can reach products more readily without requiring a large increase in temperature.
Enzymes are not consumed in the reaction and can be reused; they can act on specific substrates repeatedly.
Enzymes are commonly named with the suffix -ase (e.g., kinase, phosphatase).
Enzyme specificity stems from the precise fit between enzyme and substrate.
Three ways enzymes affect substrates to form products
Bonding substrates together to form a product (synthetic reaction).
Breaking substrates apart to form multiple products (cleavage).
Rearranging substrates to form an isomer or alternate product (rearrangement).
Why enzymes are needed in homeostasis
Without enzymes, many reactions would proceed too slowly at body temperature; to speed them up sufficiently, you would otherwise need higher temperatures, which would disrupt homeostasis.
Enzymes allow necessary metabolic pathways to run efficiently at normal body temperatures.
Enzyme properties: specificity, reuse, and nomenclature
Enzymes are highly specific: each enzyme acts on particular substrates to produce specific products.
Enzymes can be reused; they are not consumed by the reaction.
Enzymes are identified by the suffix -ase (e.g., kinase, phosphatase).
Models of how enzymes interact with substrates
Lock-and-key model:
Substrate fits precisely into the enzyme's active site like a key in a lock.
The product is released; mechanism explains forward reaction well but struggles to explain reverse reaction and how products can rebind for the reverse reaction.
Induced-fit model:
Substrate binds to the enzyme not in perfect fit; the enzyme adjusts its shape to better fit the substrate.
After catalysis, the product is released; this model better explains how reverse reactions may occur.
Cofactors and coenzymes in enzyme activity
Cofactors:
Often trace metals (e.g., magnesium, zinc) incorporated into the enzyme's structure.
Charge-bearing cofactors can help attract oppositely charged substrates and assist binding.
Coenzymes:
Small organic molecules often derived from vitamins; they transfer small chemical groups (e.g., hydrogen).
Examples: NAD and FAD; NADH and FADH participate in the citric acid cycle to help generate ATP.
Coenzymes shuttle hydrogen and other groups between reactions.
Saturation kinetics and the factory analogy
Think of a cell as a factory with enzymes as workers and yarn as substrate.
If you have 100 workers and 100 yarn pieces, all workers can operate simultaneously to produce 100 scarves at once (maximum rate).
If you have fewer yarns, not all workers can work; increasing substrate beyond the number of workers does not increase the rate beyond the maximum (saturation).
Saturation point (Vmax): the maximum rate achieved when all enzymes are working at their maximum capacity.
Increasing substrate concentration increases rate up to saturation; increasing enzyme concentration increases the maximum rate (Vmax).
Substrate affinity affects how quickly saturation is reached:
Higher binding affinity between substrate and enzyme leads to reaching saturation more quickly.
Lower affinity requires more substrate to reach the same rate.
Regulation of enzyme activity
Cells regulate enzyme activity to meet changing demands; there are two main regulatory strategies discussed:
Allosteric regulation
Enzymes with two binding sites:
Active site: where the substrate binds.
Regulatory (allosteric) site: where a modulator binds.
Modulators (ligands) bind reversibly to the regulatory site and alter the enzyme's shape, changing the active site's affinity for the substrate.
Outcomes:
Allosteric activator increases substrate affinity and reaction rate; saturation is reached sooner.
Allosteric inhibitor decreases substrate affinity and reaction rate; saturation is reached later or not at all under the same substrate conditions.
Allosteric enzymes can have two forms of regulation, leading to different sigmoidal kinetics compared with simple Michaelis-Menten behavior.
Covalent regulation
Enzyme activity is turned on or off by covalent modification, typically via phosphorylation or dephosphorylation.
Process involves a covalent bond between a chemical group and the enzyme, changing its shape and activity.
Key players:
Kinase: adds a phosphate group (phosphorylation).
Phosphatase: removes a phosphate group (dephosphorylation).
Common chemical group used: phosphate (from ATP).
Example sequence:
Kinase transfers a phosphate from ATP to a target protein (enzyme), forming a phosphorylated enzyme that may be active or inactive depending on the system.
Phosphatase removes the phosphate, reversing the effect.
General reaction depiction:
Kinase action: ext{ATP} + ext{substrate}
ightarrow ext{ADP} + ext{phosphorylated substrate}Phosphatase action: ext{phosphorylated substrate}
ightarrow ext{substrate} + ext{Pi}
ATP is commonly the phosphate donor; its hydrolysis to ADP provides the phosphate group used in covalent regulation.
Key enzymes and terminology
Kinases: enzymes that phosphorylate other proteins (suffix -ase).
Phosphatases: enzymes that remove phosphate groups (suffix -ase).
The dynamic interplay between kinases and phosphatases provides a reversible switch to regulate enzyme activity and metabolic pathways.
Mathematical and conceptual notes (LaTeX-formatted)
Activation energy concept:
Activation energy barrier: (E_a)
Lowering (Ea) increases reaction rate; higher (Ea) slows it down.
Temperature and rate (Arrhenius-like relation, conceptual):
For many reactions, rate constant (k) increases with temperature and decreases with higher (E_a):
Conceptual representation: k \,\propto\, e^{-\frac{E_a}{RT}}
Where (R) is the gas constant and (T) is temperature in Kelvin.
Temperature references from transcript:
Normal body temperature: 37^{\circ}\mathrm{C}
Approximate normal human body Fahrenheit equivalent: 98.6^{\circ}\mathrm{F}
Examples: external heat ~110^{\circ}\mathrm{F}; external cold ~30^{\circ}\mathrm{F}
In balance, body temperature is within \pm 1^{\circ}\mathrm{C} of the set point.
ATP hydrolysis and phosphate transfer (simplified):
Kinase step: \text{ATP} + \text{substrate} \rightarrow \text{ADP} + \text{phosphorylated substrate}
Phosphatase step: \text{phosphorylated substrate} \rightarrow \text{substrate} + \text{P_i}
Enzyme saturation concept (Vmax):
Saturation occurs when all enzymes are bound and operating at maximum capacity; increasing substrate beyond this point does not increase rate.
Substrate affinity and saturation: higher affinity means faster approach to saturation; lower affinity means slower approach.
Connections to broader concepts
Homeostasis integrates signals across systems (nervous and endocrine) to maintain internal stability.
The nervous system provides rapid regulation; the endocrine system provides slower but sustained regulation.
Regulatory mechanisms (allosteric and covalent) allow dynamic tuning of metabolic pathways in response to changing physiological demands.
Enzyme kinetics underlie most physiological processes, including metabolism, signal transduction, and tissue homeostasis.