Metabolism: The Big Picture
For all chemical or biochemical reactions or conversions there is an equilibrium. Every biomolecule that has multiple paths of reaction is involved in multiple equilibria. However, biochemical systems are generally not at equilibrium. Living organisms can be considered as systems maintaining semi-stable states of disequilibrium. The energy input (e.g. sunlight for plants, or food for microbes and animals) is used to help maintain the system in the semi-stable disequilibrium. While the organism is alive, its complex network of biochemical reactions is kept from equilibrium. After an organism dies, all of its reactions move toward equilibrium. Equilibrium is death!
Do not confuse equilibria and rates of reactions. Every reaction has an equilibrium that determines the tendency of the reaction to proceed to the right or the left as written. The equilibrium constant is constant and is a function of the free energy change for that written equation. The rate of the reaction is not a constant and is not directly related to the Keq. Consider a sandwich. Sitting on a plate, it looks quite stable. Place it in a beaker of water and it will look soggy, but stable. Leave it for several hours and it appears to be unchanged. The sandwich is composed of biopolymers such as polysaccharides and proteins. These classes of molecules are composed of sugar and amino acid residues linked by glycosyl and amide bonds, respectively. Each polysaccharide and protein molecule can react with water, causing hydrolysis of the glycosyl or amide bonds and producing free sugars and amino acids. Because energy is released by the hydrolysis, the equilibrium state for the hydrolysis of polysaccharides and proteins lies far in the direction of the hydrolysis products.
Polysaccharide + H2O sugars + free energy Protein + H2O amino acids + free energy
Polysaccharide + H2O sugars + free energy
Protein + H2O amino acids + free energy
However, the system (the sandwich in a beaker of water) does not normally contain sufficient activation energy to initiate the process. Thus the sandwich, although far away from its equilibrium state, appears to be stable.
All organisms are heterotrophs. They rely on the oxidation of reduced carbon compounds for energy. Autotrophs use energy to reduce CO2 so that they can have reduced carbon compounds that they can oxidize and produce biological energy. Photoautotrophs (plants) make starch during the day so that they can live as heterotrophs and survive during the dark night.
Oxidation of reduced carbon compounds releases free energy and is exergonic and increases entropy.
Photosynthesis and Respiration are part of a global cycle driven by the sun.
(CH2O)n + O2 CO2 + H2O + energy
Reduction and Oxidation
Reduction and oxidation is one of those topics which many students find difficult because it can be viewed in different ways. At its most simple level, reduction is the gain of electrons whereas oxidation is the loss of electrons. Because electrons are real when one molecule is reduced, another molecule is oxidized. The two such molecules would be called a redox couple. Redox reactions in biological systems can involve transfer of only electrons as in the case of cytochrome c. Notice that in the case of cytochrome c, only one electron is transferred during oxidation or reduction.
The following is an oxidation, since electrons are lost.
Reduced Cyt c (Fe2+) ---> Oxidized Cyt c (Fe3+) + e-
The following is a reduction, since electrons are acquired.
Oxidized Cyt c (Fe3+) + e- ---> Reduced Cyt c (Fe2+)
Oxidation can also be represented as the simultaneous loss of electrons (e-) and protons (H+). Sometimes this is represented as the loss of a combined hydrogen and electron termed the hydride ion (H:-). Thus we could write the oxidation of ethanol to acetaldehyde as either
CH3CH2OH ---> CH3CHO + 2H+ + 2e- or CH3CH2OH ---> CH3CHO + H:- + H+
CH3CH2OH ---> CH3CHO + 2H+ + 2e-
or
CH3CH2OH ---> CH3CHO + H:- + H+
Notice that in this case, the transfer involves two electrons (or one hydride ion). You will see many two electron transfers in metabolism. Such transfers often are catalyzed by enzymes that use cofactors such as NAD, NADP, FMN or FAD. When you see these cofactors involved in an enzyme-catalyzed reaction, you can infer that the oxidation or reduction will involve two electrons.
Since many biochemical oxidations involve the loss of protons, we can often visually inspect molecules and infer which is the most oxidized. Study the following examples.
Where do all these electrons go? In anaerobic organisms the trick is to make some molecules more oxidized (toxic waste products like lactate) and extract a little energy. In aerobic organisms, they can dump all their electrons into O2 and produce H2O, extracting a lot of energy with no waste products.
Metabolism is complex.
Metabolism is the sum of all the reactions carried out within a cell, tissue or organism. It includes both catabolic reactions which are involved in the breakdown of macromolecules and oxidation of reduced organic molecules to release energy, and anabolic reactions which require energy to produce more reduced molecules and synthesize polymeric macromolecules. The anabolic and catabolic pathways are tightly coupled to one another.
Metabolism tends to be organized into a series of sequential reactions, each of which produces a small change to the metabolite which is the product of the previous reaction. Each reaction is catalyzed by a distinct enzyme. Because overall metabolism is broken down into a series of small reactions, the amount of energy released or required for each step is small enough to be possible at the temperatures and pressures found in cells.
The overall flow of metabolites through a metabolic pathway is termed a flux. Metabolic flux is generally tightly controlled by modulation of key enzyme activities. Allosteric regulation means regulation by effectors that are often substrates, products, or coenzymes of the pathway but not necessarily of the enzyme in question. Enzymes are often modulated by being sensitive to allosteric regulation by molecules which sense the overall energy availability within the cell (e.g. ATP or NADH) or the general balance between anabolism and catabolism. Enzymes can also be negatively regulated by products farther down the same metabolic pathway (feedback inhibition) or positively regulated by metabolites up the metabolic pathway (feed-forward activation). Some enzymes are also modulated by some sort of covalent modification (e.g. phosphorylation).
Competing metabolic pathways in eukaryotes are often carried out in different compartments.
Major Catabolic Pathways
Major Anabolic Pathways
Major Energy Transduction Mechanisms
Anabolism and catabolism are bioenergetically coupled. Part of the energy released by catabolism is conserved in ATP and NADH or NADPH. These molecules are used to keep metabolism poised at disequilibrium and fuel anabolism. Because the concentrations of these energy-mediating molecules is of critical importance, they are carefully monitored by all pathways and processes. All pathways respond in a manner that tends to keep ATP and NAD(P)H concentrations high and relatively constant. If their concentrations are high, anabolism is activated; if their concentrations are low, anabolism is inhibited. If their concentrations begin to decrease, catabolism is stimulated (to produce more ATP & NAD(P)H); when their concentrations are high again, catabolism slows.
Adenylate kinase helps stabilize [ATP]. When [ATP] starts to decrease, [ADP] increases and produces more ATP.
ATP + AMP <---> ADP + ADP
Pathways and fluxes are regulated by the modulation of relatively few enzymes. Regulated enzymes tend to catalyze reactions with a significant decrease in free energy, and are usually located near the beginning of a pathway or following a metabolic fork. If pathways were not regulated, anabolism and catabolism would both occur simultaneously and the energy from catabolism would be lost by a futile cycle of reduction and oxidation, of building macromolecules and hydrolyzing them.
Not all metabolic fluxes occur in linear pathways. Some are accomplished with cycles. Metabolic cycles can be either anabolic or catabolic. Examples include the Citric Acid cycle, the glyoxylate cycle and the urea cycle. In addition to control of key enzymes in a metabolic cycle, there is an additional regulatory mechanism that is not present in linear pathways. The concentration of the intermediates in the cycle can be increased or decreased. Since the cycle is closed, it acts like a catalyst. If the concentration of intermediates is increased, the rate of the overall reaction catalyzed by the cycle will increase. Similarly, if the concentration of metabolic intermediates in the cycle is decreased, the overall reaction catalyzed by the cycle will decrease.
WWW Sites for metabolic pathways:
