By GERARD CHRETIEN BIOLOGY
Several principles govern metabolic pathways in the cell:
A. Complex chemical transformations in the cell do not occur in a single reaction, but in a number of small steps that are connected in a pathway.
B. Each reaction is catalyzed by a specific enzyme.
C. Metabolic pathways is catalyzed by a specific enzyme.
D. Many metabolic pathways are compartmentalized, with certain steps occurring inside an organelle.
E. Metabolic pathways in organisms are regulated by the activities of a few enzyme.
Obtaining Energy and Electrons from Glucose
The most common fuel for living cells is the sugar Glucose.
Cells trap energy while metabolizing glucose
If glucose is burned in a flame, it readily forms carbon dioxide, water, and a lot of energy—-but only if oxygen gas(O2) is present. The balance equation for this combustion reaction is:
C6 H12 O6 + 6 O2 —- 6 CO2 + 6 H2O + ENERGY (HEAT AND LIGHT)
This same equation applies to the metabolism of glucose in cells, except that metabolism is a multi-step, controlled series of reactions, ending up with almost half of the energy captured in ATP.
Three metabolic processes play roles in the utilization of glucose for energy: GLYCOSIS, CELLULAR RESPIRATION, AND FERMENTATION.
A. Glycosis is a series of reactions that begins the metabolism of glucose in all cells and produces the three-carbon product pyruvate. A small amount of the energy stored in the glucose is released in usable form.
B. Cellular Respiration occurs when the environment is aerobic (contains oxygen gas , O2), and essentially converts pyruvate to carbon (CO2). In the process, a great deal of the energy stored in the covalent bonds of pyruvate is released and trapped in ATP.
C. Fermentation occurs when the environment is anaerobic (lacking in O2). Instead of energy-poor CO2, relatively energy-rich molecules such as lactic acid or ethanol are produced, so the energy extracted from glucose is far than under aerobic conditions.
Redox reactions transfer electrons and energy
a.Reaction in which one substance transfers one or more electrons to another substance is called an oxidation-reduction reaction, or redox-reaction.
The gain of one or more electrons by an atom, ion, or molecule is called reduction. The loss of one or more electron is called oxidation.
Oxidation and reduction always occur together.
In a redox reaction, energy is transferred.
The coenzyme NAD is a key electron carrier in redox reactions
The main pair of oxidizing and reducing agents in cells is based on the compound NAD (NICOTINAMIDE ADENINE DINUCLEOTIDE).
An Overview: Releasing Energy from Glucose
The three energy-extracting processes of cells may be divided into distinct pathways:
A. When O2 is available as the final electron acceptor, four pathways operate. Glycosis takes place first, and is followed by the three pathways of cellular respiration: pyruvate oxidation, the citric acid cycle, and the respiration.
B.When O2 is unavailable , pyruvate oxidation, the citric acid cycle , and the respiratory chain do not function, and fermentation is added to the glycolytic pathway.
In prokaryotes, the enzymes the used in glycolysis, fermentation, and the citric acid cycle are soluble in the cytosol.
In eukaryotes, glycosis and fermentation take place in the cytoplasm outside of the mitochondria.
Glycosis begins the breakdown of glucose.
Cellular Respiration operates when O2 is available, yielding Co2 and H2o as products.
In pyruvate oxidation, the end product of glycosis(pyruvate) is oxidized to acetate, which is activated by the addition of a coenzyme and further metabolized by the citric acid cycle.
The Citric Acid cycle is a cycle series of reactions in which the acetate becomes completely oxidized, forming Co2 and transferring electrons (along with their hydrogen nuclei) to carrier molecules.
The fourth energy-extracting pathway for aerobic cells is the Respiratory Chain., which releases energy from the reduced NADH+H+ in such a way that it can be used to form ATP.
Glycosis:From Glucose to Pyruvate
Glycosis can be divided into two groups of reactions: energy-investing reactions that use ATP, and energy-harvesting reactions that produce ATP.
The energy-investing reactions of glycolysis require ATP
The first five reactions are endergonic; that is, the cell is investing free energy rather than gaining it during the early reactions of glycosis.
A kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to another substrate.
The energy-investing reactions of glycolysis yield ATP and NADH + H+
Substrate-Level Phosphorylation is called substrate-level phosphorylation
Glycolysis May Be Allowed By Fermentation
A review of the glycolytic shows that the beginning of glycolysis, two molecules of ATP are used per molecule of glucose, but that ultimately four molecules of ATP are produced (two for each of the two BPG molecules)- a net gain of two ATP molecules and two NADH + H+
When fermentation follows glycolysis, the total usable energy yield is just these two ATP molecules per glucose molecule.
In eukaryotes, these reactions take place in the mitochondria.
The oxidation of pyruvate to acetate is link between glycolysis and cellular respiration. Pyruvate oxidation is a multi-step reaction catalyzed by an enormous enzyme complex that is attached to the inner mitochondria membrane.
There are three steps in this oxidation reaction:
A. Pyruvate is oxidized to the acetyl group, and Co2 is released.
B. Part of the energy from the oxidation in the first step is saved by the reduction of NADH+ to NADH+ H+.
C. Some of the remaining energy is stored temporarily by the combining of the acetyl group with CoA.
The Citric Acid Cycle
Acetyl CoA is the starting point for the citric acid cycle (also called the Krebs cycle or the tricarboxylic cycle). This pathway, which consist of eight reactions, completely oxidizes the two-carbon acetyl group to two molecules of carbon dioxide. The free energy released from these reactions is captured by NAD, FAD, ADP.
THE principle inputs to the citric cycle are acetate(in the form of acetyl CoA), water, and oxidized electron carriers. The principal outputs are carbon dioxide and reduced electron carriers. Overall, for each acetyl group, the citric acid cycle removes two carbons as CO2 and uses four, the pairs of hydrogen atoms to reduce carrier molecules.
The citric acid cycle produces two Co2 molecules and reduced carriers
At the beginning of the citric acid cycle , acetyl acetylCoA, whicjh has two carbon atoms in its acetyl group, reacts with a four-carbon acid , oxaloacetate, to form the six-carbon compound citrate (citric acid). The remainder of the cycle consists of a series of enzyme -catalyzed reactions in which citrate is degraded to a new four-carbon molecule of oxaloacetate.
The citric acid cycle is maintained in a steady state-that is, although materials enter and leave intermediate compounds are formed as they are metabolized, the concentrations of molecules in the cycle do not change much.
The energy temporarily stored in acetyl CoA drives the formation of citrate form oxaloacetate(reaction 1).
Although most of the enzymes of the citric acid cycle are dissolved in the mitochondrial matrix, there are two exceptions: succinate dehydrogenase, which catalyzes reaction 6, and ketoglutarate dehyrogenase, which catalyzes reaction 4.
The Respiratory Chain: Electrons, Protons Pumping, and ATP
Without NAD+ and FAD, the oxidative steps of glycosis, pyruvate oxidation oxidation, and the citric acid cycle could not occur.
The story has three parts:
A.First, the electrons pass through a series of membrane-associated electron carriers called the respiratory chain.
B.Second, the flow of electrons along the chain causes the active transport of protons across the inner mitochondria membrane, out of the matrix, creating a concentration gradient.
C. Third, the protons diffuses back into the mitochondrial matrix through a proton channel, which couples this diffusion to the synthesis of ATP.
THE overall process of ATP synthesis resulting from electron transport through the respiratory chain is called oxidative phosphorylation.
The respiratory chain transports electron and releases energy
The respiratory chain contains three components:
A.Three large protein complexes, containing carrier molecules and their associated enzymes
B. A small protein called cytochrome c
C. A nonprotein component called ubiquinone(Q)
The large protein complexes are bound to the folds of the inner mitochodrial membranes, the cristae, in eukayotes, or to the plasma membrane of aerobic prokayotes.
Active proton transport is followed by diffusion coupled to ATP synthesis
As we have seen, all the carriers and enzymes of the respiratory chain (except cytochrome c) are embedded in the inner mitochondrial membrane.
Together, the proton concentration gradient and the charge difference constitute a source of potential energy called the proton-motive force.This force tends to drive the protons back across the membrane, just as the charge on a battery drives the flow of electrons, discharging the battery.
The conversion of the proton-motive force into kinetic energy is prevented by the fact that the lipid bilayer of the inner membrane is impermeable to protons. However, they can diffuse across the membrane by passing through a specific channel protein, called ATP SYNTHASE, that couples proton movement to the synthesis of ATP. This coupling of proton-motive and ATP synthesis is called the chemiosmotic mechanism.
The Chemiosmotic Mechanism Couples Electron Transport to ATP Synthesis
A. The flow of electrons from NADH(OR FADH2) from one electron carrier to another in the respiratory chain is a series of exergonic reactions that occurs in the inner mitochondrial membrane.
B.These exergonic reactions drive the endergonic pumping of H+out of the mitochondrial matrix and across the inner membrane into intermembrane space. This pumping forms a H+ gradient.
C. The potential energy of the H+ gradient, or proton-motive force, is harnessed by ATP synthase. This protein has two roles:IT acts as a channel allowing the H+ to diffuse back into the matrix, and it uses the energy of that diffusion to make ATP from ADP AND Pi:
ATP—ADP + Pi + free energy
If the reaction goes to the right, free energy is released and is used to pump H+ out of the mitochondrial matrix. If the reaction goes to left, it uses free energy from H+ diffusion into the matrix to make ATP.
Proton Diffusion Can BE UNCOUPLED FROM ATP PRODUCTION
For the chemiosmotic mechanism to work, the diffusion of H+ and the formation of ATP must be tightly coupled; that is , the protons must through the ATP synthase channel in order to move inward.
FERMENTATTION: ATP FROM GLUCOSE, WITHOUT O2
Under anaerobic conditions, many (but not all)cells can continue to carry out glycolysis and produce a limited amount of ATP by FERMENTATION. This process occurs in the cytoplasm with glycolysis.
Fermentation has two defining characteristics. First, it uses NADH+H+ formed by GLYCOLYSIS to reduce pyruvate or one of its metabolites, and consequently NAD+ is regenerated. Second, fermentation enables glycolysis to produce a small but sustained amount of ATP;
Some fermentating cells produce lactic acid and others produce alcohol
Many different types of fermentation are carried out by different bacteria and eukaryotic body cells. These different fermentations are distinguished by the final product produced. For example, in lactic acid fermentation, pyruvate is reduced to lactate.
Certain yeasts and some plant cells carry on a process called Alcoholic Fermentation under anaerobic conditions
Contrasting Energy Yields
The total net energy yield from fermentation is two molecules of ATP per molecules of glucose oxidized. Fermentation is an incomplete oxidation of glucose. The total gross yield of ATP from one molecule of glucose taken through glycolysis and cellular respiration is 38.
Glycolysis and the respiratory pathways do not operate in isolation from the rest of metabolism. Rather, there is an interchang, with biochemical traffic flowing both into these pathways and out of them, to and from the synthesis and breakdown of amino acids, nucleotides, fatty acids and so forth.
Catabolism and Anabolism invovle interconversions using carbon skeletons
Polysaccharide, lipids, and proteins can all be broken down to provide energy.
A. Polysaccharide are hydrolyzed to glucose phosphate, an intermediate in glycolysis. This molecule then passes through the rest of glycolysis and the citric acid cycle,where its energy is extracted in NADH and ATP.
B. Lipids are converted to their substituents, glycerol and fatty acids. Glycerol is converted to dihydroxyacetone phosphate, an intermediatein glycolysis, and fatty acids to acetate and then acetyl CoA in the mitochondria. In both cases, further oxidation to CO2 and release of energy of energy then occur.
C. Proteins are hydrolyzed to their amino acid building blocks. The 20 amino acids feeds into glycosis or the citric acid cycle at different points.
Catabolism and Anabolism are Integrated
Glucose is an excellent source of energy. Polysaccharides and fats have no such catalytic roles. The level of acetylCoA rises as a fatty acids are broken down.
Allostery regulates metabolism
Glycolysis, the citric acid cycle, and the respiratory chain are regulated by allosteric control of the enzymes involved. The main control point in glycolysis is the enzyme PHOFRUCTOKINASE. The main control in the citric acid cycle is the enzyme ISOCITRATE DEHYROGENASE, which converts isocitrate to ketoglutarate..