1. An Introduction to Metabolism
Chapter 8

2. The chemistry of life is organized into metabolic pathways
Metabolism -- chemical processes in an organism; processes material and energy.
Metabolic pathways are orderly series of enzymatically controlled reactions; Two types:
Catabolic pathways -- release energy by breaking down complex molecules to simpler compounds (cellular respiration).
Anabolic pathways -- consume energy to build complicated molecules from simpler ones (photosynthesis).
Metabolic reactions may be coupled, so that energy released from a catabolic reaction can be used to drive an anabolic one.

4. The energy transformations of life are subject to two laws of thermodynamics
• Kinetic energy of sunlight can be transformed into the potential energy of chemical bonds during photosynthesis.
• Potential energy in the chemical bonds of gasoline can be transformed into kinetic mechanical energy which pushes the pistons of an engine.
First Law of Thermodynamics -- Energy can be transferred and transformed, but it cannot be created or destroyed.
Second Law of Thermodynamics – Each step in energy transfer or transformation makes the universe more disordered (increases entropy).

5. Energy and Chemical Reactions
G = H – TS (where T is a certain temperature)
G or Free Energy -- Amount of energy that is available to do work.
H -- total energy in the system (enthalpy).
S -- energy not available for work (entropy).
Exergonic reaction -- A reaction that proceeds with a decrease of free energy; spontaneous; enthalpy decreases and entropy increases. (∆G is negative)
Endergonic reaction -- An energy-requiring reaction that proceeds with an increase of free energy; enthalpy increases and entropy decreases. (∆G is positive)

6. Exergonic / Endergonic

7. ATP powers cellular work
1. Mechanical work: beating of cilia, muscle contraction, cytoplasmic flow, and chromosome movement during mitosis and meiosis.
2. Transport work: pumping substances across membranes.
3. Chemical work: endergonic process of polymerization.

8. ATP Structure
ATP (adenosine triphosphate) -- Nucleotide with unstable, high-energy phosphate bonds. ATP consists of:
• Adenine, a nitrogenous base.
• Ribose, a five-carbon sugar.
• Chain of three phosphate groups.
Bonds between the phosphate groups can be hydrolyzed in an exergonic reaction that releases energy; coupled with other endergonic rxns in cells.
ATP H2O ————»ADP Pi

9. The Regeneration of ATP
ATP rapidly, continually regenerated by the cell. (10 molecules used and regenerated/sec/cell).
Energy to do this comes from cellular respiration.
Reverse of hydrolysis  condensation rxn.
Occurs in mitochondria.

11. Enzymes speed up metabolic reactions
Biochemical reactions require enzymes to speed up and control reaction rates.
Catalyst -- Chemical that accelerates a reaction without being permanently changed.
Enzymes -- Biological catalysts; usually proteins (and some RNA).
Free energy of activation (Activation energy) -- Amount of energy that reactant molecules must absorb to start a reaction (EA).

12. Enzymes are substrate-specific
Depends upon the enzyme's three-dimensional shape.
Substrate -- Substance an enzyme acts on and makes more reactive.
Substrate + enzyme  enzyme-substrate complex  product + enzyme
Active site -- region of an enzyme molecule which binds to the substrate.
• Usually a pocket or groove on the protein's surface.
• Formed with a few of the enzyme's amino acids.
Induced fit -- Change in the shape of an enzyme's active site, which is induced by the substrate to enhance ability to interact.

13. Clip

15. Chemical and physical environment affects enzyme activity
Temperature and pH
Reaction rate increases with increasing temperature. Kinetic energy increases, which increases substrate collisions with active sites.
Enzyme denatures when weak bonds are disrupted, changing conformation.
H+ concentration can also disrupt hydrogen bonding within the enzyme.
Optimal temperature range of most human enzymes is 35°- 40°C.
Optimal pH range for most enzymes is pH 6-8.

16. Chemical and physical environment affects enzyme activity
Cofactors
Small nonprotein molecules that are required for enzyme activity.
• May bind tightly to active site.
• May bind loosely to both active site and substrate.
• Some are inorganic (metal atoms of zinc, iron or copper).
• Some are organic and are called coenzymes (most vitamins).

19. Chemical and physical environment affects enzyme activity(cont)
Enzyme Inhibitors
Competitive inhibitors -- Chemicals that resemble an enzyme's normal substrate and compete with it for the active site.
Noncompetitive inhibitors -- Do not enter the enzyme's active site, but bind to another part of the enzyme molecule.
• Causes enzyme to change its shape so the active site cannot bind substrate.
Many drugs and poisonous substances are inhibitors. Aspirin inhibits production of prostaglandins. Penicillin inhibits cell wall formation in bacteria.

20. Chemical and physical environment affects enzyme activity(cont)
Allosteric Regulation
Allosteric site -- Specific receptor site on some part of the enzyme molecule other than the active site; found in enzymes with two or more polypeptide chains.
Binding of an activator to an allosteric site results in an active conformation.
Binding of an inhibitor to an allosteric site results in an inactive conformation.

24. Chemical and physical environment affects enzyme activity(cont)
Cooperativity
Substrate binding to the active site of one subunit changes shape of the enzyme; enhances substrate binding at the active sites of the other subunits.

25. Feedback Inhibition
Regulation of a metabolic pathway by its end product, which inhibits an enzyme within the pathway.
Cells do not make more product than necessary.

26. Clip