jimtrue.com : school : BSC2010 : CH 06: Introduction to Metabolism

Posted by Jim True on February 3, 2004 5:23 AM. Last Updated October 22, 2006 9:23 PM

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CH 06: Introduction to Metabolism

Metabolic Pathways

Up to this point we've talked about the building blocks; metabolism is one of the first of the 'cellular processes' we will discuss. You need to understand process; it can't be memorized. Metabolism is not possible without energy.

• As mentioned before, metabolism is the sum total of all chemical and physical processes in living organisms.
• If you understand that:
  • ALL chemical reactions (which can also result in the building and breakdown of physical structure) involve electrons being transferred or shared via chemical bonds, and;
  • Electrons represent potential energy
• Then, metabolism is the sum total of all energy relationships in an organism.
• Even the simplest cells will have a tremendous number of metabolic reaction. (Figure 6.1, p.88)
• Some of these involve the breakdown of complex molecules into simpler ones (catabolism) [hydrolysis], while others involve the construction of larger molecules from smaller (anabolism) [dehydration synthesis].
• With respect to energy, catabolic reactions typically release energy while anabolism stores energy. Working off food by exercizing is 'catabolizing the food'; creating glycogen is a result of anabolic reactions.
• Cells will typically use energy released by catabolism to drive anabolism; you digest food to give you the energy to walk, think, etc.
• Even so, as we will see, living things must have an outside original source of energy to draw from in order to allow the metabolic reactions to continue. Energy does not just 'spring into being' and 'vanish into nothing'. The way energy is captured, converted and used differs among different lifeforms.

Energy

• Energy -- Capacity to do work (put mass in motion).
• Potential Energy -- Stored energy, energy that is available to do work. Anabolism results in Potential energy.
• Kinetic Energy -- Energy in action, work is being performed. Kinetic energy can draw on Potential Energy for fuel.
• Kinetic Energy can take one of three general forms:
  • Electrical -- Energy moves as a current between charged particles (ionic particles, electrolytes) e.g. nervous system impulses, and to a lesser extent the muscular system.
  • Chemical -- Energy released or absorbed by the breaking or making of chemical bonds, e.g. cellular respiration and photosynthesis (in part).
  • Radiant -- Energy is propagated as a waveform, e.g. light, x-ray, radio, ultraviolet, gamma waves.
• As we will see, all three of these will play varying roles in living systems.
• All forms of energy can be converted to a form of radiant energy called Heat -- amount of kinetic energy a substance possesses.
• Heat can be measured. Temperature - a measure of the heat energy of a substance or system. (Celsium 100 boiling point of water; 0 is freezing point of water, Fahrenheit, Kelvin)
• System -- Term used to describe the matter being studied. A cell is a system, your body is a system, the solar system is a system.
• Surroundings -- everything outside the specific system.
• Closed System -- A system that is isolated from its surroundings.
• Open System -- Energy can be transferred between the system and its surroundings. Nothing can generate its own energy source.
• Living organisms are open systems. Regardless of the scale we are looking at.
• Calorie (cal) -- the basic unit measure of heat energy. It is the amount of heat energy needed to raise 1g of water by 1 degree C.
• Kilocalorie (kcal) -- Equals 1000 calories. This is the standard unit of measure for heat energy in biological systems.
• For nutritionists and biologists, the calorie (c) = 1 kcal. Biological calorie is much larger than the physical calorie.

Thermodynamics

• Thermodynamics ("Therm" -- heat + "dynamo" -- energy) -- the physical study of energy transformations that occur in matter (a branch of physics).
• There are two physical laws that apply to ALL energy transformations:
  • 1st Law of Thermodynamics (AKA the Law of Conservation of Energy) -- The Total amount of energy in the universe is constant, therefore the total amount of energy in any system is constant.
    • the 1st law basically states that energy can neither be created nor destroyed, only transformed.
    • The transformation of energy is never perfect. Disorganized heat energy is known as 'entropy'.
    • Some energy in a system may not be able to be converted from one form to another, but even if all energy is converted, some energy is ALWAYS lost in the conversion process! Its in a form that can't be transformed.
  • 2nd Law of Thermodynamics -- All systems tend towards entropy -- disorder. As energy is transformed, a system tends toward entropy because of heat loss.
    • Solar system springs into being; every living process uses a portion of that energy, and loses a portion to entropy. Percentage of usable energy is dropping and percentage of entropy is rising.
    • Application of energy maintains order. Showering, shaving, putting on clean clothes. If you don't maintain that system, disorder arises in a very short time.
• Because of these two laws, for any system, including biological systems, a continual input of energy is always required to maintain order (organization) in the system.

Free Energy and Work

• Free Energy -- the amount of energy in a system available to do work.
• In living systems (as with all systems), all physical and chemical processes (metabolism in living organisms) proceed in a direction where available free energy decreases and entropy increases.
• The greater the amount of free energy, the less stable a system is. All systems will tend towards increased stability.
• In order to do this, free energy is used, ie. work is performed.
• Equilibrium -- the point of stability. The free energy has been used in performing work to the point where the system is stable.
• In chemical reactions, this would be where the rate of:
  • A + B --> C = C --> A + B, thus
  • A + B < -- > C
• More free energy, less stable, greater work capacity --> Less free energy, more stable, less work capacity.
• The problem is that once equilibrium is reached, work stops because the free energy to do work has been used up, the system is stable.
• Thus, systems tending TOWARDS equilibrium have free energy to do work and will do so SPONTANEOUSLY, i.e., without any additional energy input. You don't have to put energy input in to go towards equilibrium, it will happen spontaneously as bodies will tend to go towards a lower state of energy. Universal Law of Laziness, ground state of matter.
• Systems tending AWAY from equilibrium require an energy input to do so, which builds their free energy content once more.
• The tendency AWAY from equilibrium is non-spontaneous.
• Because energy must be input to do this, and because ANY energy transformation is subject to the Laws of Thermodynamics, energy input to keep a system from equilibrium must always occur!

Free Energy & Metabolism

• The more free energy a system has the more stable it is; cells need an unstable environment to thrive.
• Chemical reactions may or may not require free energy to proceed.
• Exergonic -- No energy is needed to start the reaction, which proceeds spontaneously. Free energy is released for use in work. Sodium exposed to one drop of water; exergonic, it will explode instantly.
• Most metabolic activities are endergonic reactions -- they require some free energy to start the reaction process.
• Free energy will be stored from endergonic reactions. Exergonic is spontaneous output of energy; endergonic requires input. Figure 6.6, p.93
• If a cell was a closed system, the metabolic reactions of exergonic and endergonic reactions would eventually reach equilibrium, there would be no further free energy available for work (life) and the cell would die.
• Fortunately, all cells are open systems and as such, can maintain what is called metabolic disequilibrium, which is a constant imbalance between exergonic and endergonic reactions so that work is always done. We need reach complete equilibrium because we always have continous input of energy from outside to maintain the energy. Teeter totter requires energy to keep the seesaw going up and down. Also have to have way to get rid of the waste process.
• Thus, cells will always need an outside energy source to keep metabolic reactions running.
• Internally, metabolism will function via energy coupling, where an exergonic reaction drives an endergonic reaction. Energy stored from endergonic reactions can then be used to drive exergonic reactions.
• In all cells, there is one basic molecule whose energy coupling reactions that drives all other metabolic energy couplings.

ATP

• The molecule AdenosineTriPhosphate is THE energy source that drives ALL metabolism in ALL living things.
• It is a nucleotide molecule composed of:
• One five carbon surgar ribose
• A double ring N base called adenine -- the combination of the sugar and the base is called adenosine
• Three phosphate functional groups - coiled tightly together with potential energy waiting to react. ATP will require hydrolysis to release energy. Converts ATP to ADP (adenosine diphosphate) with a large release of energy. This energy is the ONLY usable energy form for metabolism.
• The free energy released as ATP is hydrolyzed is used for three types of cellular work:
  • Mechanical -- actual physical actions of cell, e.g. locomotion
  • Transport -- The pushing of substances across cell membranes against their normal direction of movement, eg "pumps"
  • Chemical -- Generating endergonic reactions that would not otherwise occur.
• ADP can be tranformed into ATP by the addition of a phosphate group through a process of dehydration synthesis.
• As the bonds between the 2nd and 3rd P groups are hydrolyzed:
  • ATP + H2O --> ADP + P release ~13 kcal of energy for cellular use (7.3 in lab tests)
• Phosphorylation -- Phosphate groups can easily be linked back together by dehydration synthesis to form ATP.
• However, this requires energy. The energy comes from catabolic reactions that release energy stored in chemical bonds. Cellular respiration is NOT breathing. The energy for this catabolic reactions comes from the food we digest.
• The most important of these catabolic reactions is cellular respiration, which we will deal with in Chapter 9. figure 6.10, p.95
• Cells can not store ATP, it is produced and broken constantly.
• Tidbit: 140 lb human, at rest, breathing and heart rate at minimum, estimated they will use 90 lbs of ATP! However, there is < 1 g present at any given time in the entire body!
• This translates to ONE MILLION molecules of ATP formed and broken every second!

Enzymes

• Enzyme -- a special group of proteins used by cells to regulate the speed of chemical reactions. any enzyme is a protein.
• An enzyme acts as an organic catalyst -- A substance that affects a chemical reaction but is not itself used by the reaction. all enzymes are catalysts; but not all catalysts are enzymes.
• As previously mentioned, any chemical reaction involves altering one or more substances by changing chemical bonds.
• Activation Energy -- Energy required to break the original bonds and start a chemical reaction. Energy required to 'kickstart' a reaction. Products require a certain amount of energy to get them unstable to react (this is the activation energy). Figures 6.12 & 6.13, p.97
• Enzymes speed up the reaction rate by lowering the amount of activation energy.
• Enzymes do not influence the direction or concentrations in any reaction.
• Enzymes can only work in a reaction that would normally occur.
• Enzymes work in liquid medium, with a certain amount of heat in that system. The molecules have kinetic energy; reactions are caused by collision. Catabolic means they are twisted in space to snap apart.
• Substrate -- The reactant substance(s) to which an enzyme temporarily links in order to speed the formation of the product(s). These are the chemical reactants; in an enzyme reaction, we call them substrates.
• Active site -- a specific shape on the enzyme where the substrate(s) bind temporarily. The binding is temporary; very very brief. Once the reaction ends, the products and enzymes are no longer attracted to each other.
• Enzyme-substrate complex -- when the enzyme and substrates are linked (this connection is extremely short).
• Some enzymes are formed by, and operate solely as, a protein molecule. Many enzymes are JUST protein.
• However some enzymes require a cofactor (usually a metal ion) to function, e.g., Cu, Zn, Fe, Mn.
• Still other proteins require a coenzyme (an organic non-protein cofactor), eg many vitamins (like Vitamin B and B Complexes).
• Enzymes operate by forming a temporary enzyme-substrate complex that is unstable.
• As the substrate(s) bind(s) to the active site, they are brought together at precisely correct orientation so that they react quickly (joining or breaking apart). After the reaction, their shape has changed and they are released.
• This is because the enzyme is attracted to the substrate(s), but once the substrate changes during the reaction, the enzyme is no longer attracted and releases the product(s). Basically, the enzyme will attract to A + B to make C, but once C is formed that enzyme is no longer playing a role. Another enzyme is used to convert C --> B + A.
• Most enzymes end in the letters 'ase'; there are some exception to this. Pepsin and Tripsin. the name prior to the 'ase' shows the substrate that they work on. Lactase --> Lactose. Protease --> Proteins. Lipase --> Lipids.
• The enzyme is not permanently changed by the reaction and so can be reused.
• Induced fit -- The enzyme active site is similar to the substrate and once the substrate binds, the enzyme changes shape to a precise fit. (Old model was 'lock and key'). Think of the concept of a funnel; substrate only has to aim towards the activator site and the enzyme will change shape to lock into the substrate.
• Enzymes operate at different rates of speed depending on their environment and the presence/absence of other substances.
• Optimum -- The condition in which an enzyme works at its fastest rate.
• We tend to focus on the human condition; the optimum environment for enzymes in the human body are not necessarily the optimum environment for all enzymes. Optimal pH for pepsin is 2, optimal pH for trypsin is 8, 10,000,000 times more acidic. In the human body, the liver dumps bile (an alkali substance) into the intestines to allow trypsin to work.
• Enzymes typically operate in very specific conditions and if these conditoins are not present, their activity may slow or stop.
• Enzyme activities can be altered or regulated in a variety of ways.
• Activator -- any condition/substance that starts or speeds up an enzyme's activity.
• Inhibitor -- any condition/substance that stops or slows an enzyme's activity.
• Denature -- Any permanent alteration of a molecule's shape. Denaturation of an enzyme destroys its ability to function. Permanently altering the nature of the molecule. With respect to enzymes, this is considered destruction of the enzyme.
• Egg whites are pure protein; quite sensitive to heat. You cannot reverse the egg from a cooked egg white back to its liquid state.
• Enzyme (are very very sensitive; because of their protein structure they can twist and alter shape quite easily when their environment changes). Enzyme is either ON or OFF; when you modify the enzyme activity they just do not function, either permanent or temporarily. This optimum enzyme activity can be regulated by:
  • Temperature -- most enzymes have a very narrow range of temperatures in which they will function.
    • Temperatures lower than optimum usually slow or stop enzyme activity temporarily.
    • Temperatures higher than normal will eventually denature the enzyme. Higher than normal will denature.
  • pH -- Most enzyme's also require very specific pH's. Changes on either side of the optimal pH add or remove H+ ions from the ENZYME, thereby altering its properties, shape and function.
    • Both low and high pH's lead to denaturation.
  • Chemical Agents -- Cause either temporary or permanent inhibition depending on the circumstances. Temperature and pH are conditions of the environment; other chemical agents, are something that causes something else to happen (agents of mutagen, cause mutations; agents of pathogen, cause pathology (disease)). Some chemical agents can be reversed.
    • Reversible Inhibition -- Two types:
      • Competitive Inhibition -- The chemical agent has a shape very similar to the substrate and "competes" with the substrate to occupy the active site. The binding to the active site is temporary and does not damage the enzyme.
      • Non-Competitive Inhibition -- Allosteric inhibitor alters enzyme shape temporarily.
        • Allosteric -- "another position/location" refers to a receptor site on the enzyme away from the active site. Attachment of a regulator to this site causes activation or inhibition. Allosteric activator causes the enzyme's active site to active; allosteric inhibitor causes the enzyme's active site to be inhibited.
    • Irreversible Inhibition -- the enzyme is denatured by the chemical inhibitor. This is the way in which many organic poisons work. Cyanide is an inhibitor and attaches itself to the enzymes responsible for ATP production.
      • Enzymes often work in teams or series, with each enzyme producing a single reaction step. Each step may have an enzyme that uses the product(s) from the previous step as its substrate, e.g. cellular respiration. Metabolic reactions are often not A+B=C; have multiple steps and series of enzymes. Most genetic disorders are due to a lack of, reduction in number of, or mutation of a specific enzyme. Very few enzymes can mediate the forward and backward sides of a chemical reaction (switch-hitter enzymes).
    • Feedback Inhibition -- an enzyme's activity, and thus a metabolic pathway, is switched off by the product.
      • As the product concentration builds, it basically switches off the reaction sequence so that no more is made until the concentration drops.
  • Cooperativity -- a form of enzyme activation that occurs in enzymes that have multiple subunits, i.e., the enzyme has two or more active sites for the same substrate. Trigger them and they're all on; or trigger them and they're all off. Cooperation (they all activate to work together, or all deactivate to NOT work together.
    • The formation of one enzyme-substrate complex causes all active sites to acquire the correct shape for linking to the substrate.
  • Enzyme systems for different organisms differ; closer the organisms are to each other, closer their enzyme systems are.

Disclaimer: These are MY notes taken from classroom lectures while I'm in the classroom. While I'm perfectly happy to share my notes with my classmates and I know I take very good notes, you should still make every effort to attend the class and TAKE YOUR OWN NOTES. I will not transcribe everything the instructor says in the classroom, and I will NEVER post pre-exam reviews. My notes will not replace the value of actually attending class and taking your own class notes.I also cannot attest to their accuracy, other than they are what was provided in the lecture; you should not reference my notes as "expert opionion" by any means, and if you notice an error or omission, please do me the favor of e-mailing me with the correction and I will re-post my notes. End of Disclaimer.