Download
1 / 43
E N D
Chem 150Unit 12 - Metabolism • Metabolism is the sum total of all the reactions that take place in a living cell. These reactions are used to extract energy and materials form the environment (catabolism), and to use this energy and these materials to produce new molecules (anabolism ) that will sustain the cell and allow it to to propagate itself. There are literally thousands of reactions involved in metabolism, but we will focus our attention on a core set of reactions that will allow us to understand some of core principals that define metabolism.
Introduction • In this unit we will look at some themes which define metabolism. • There are literally thousands of chemical reactions that take place in a living cell • If you wrote the chemical equations for all of these reactions down on a single piece of paper, it would look something like this: View the Metabolic Chart
Introduction • Some of the themes include: • The reactions are arranged into pathways, where the product for one reaction is the reactant (substrate) for the next reaction. • The arrangement of reactions looks very much like a wiring diagram, but instead of tracing the flow of electrons, the metabolic pathways trace the flow of atoms and molecules. • Every chemical reaction in metabolism is catalyzed by an enzyme. • The enzymes are used like valves to control the flow of material through the pathways. • Nonspontaneous reactions are driven by coupling them to spontaneous reactions. • An outside source of energy is needed drive metabolism
Pathways, Energy, and Coupled Reactions • Metabolic reactions are arranged in pathways • The product of one reaction is the substrate for the next reaction in the pathway. • There are different topologies for metabolic pathways.
Pathways, Energy, and Coupled Reactions • The molecules that are placed along the pathway are the intermediates in the reactions • Other reactants and products are usually represented by side arrows • This reaction equation could also be written as
Pathways, Energy, and Coupled Reactions • When two reactions are connected through a common intermediate, they are said to be coupled. • The coupling of reactions allows spontaneous reactions to drive nonspontaneous reactions.
Pathways, Energy, and Coupled Reactions • The phosphorylation of ADP can be coupled to the dephosphorylation of 1,3-Bisphosphoglycerate:
Pathways, Energy, and Coupled Reactions • The phosphorylation of ADP can be coupled to the dephosphorylation of 1,3-Bisphosphoglycerate:
Overview of Metabolism • Metabolism • The sum of all reactions that take place in a living organism. • Metabolism = Catabolism + Anabolism • Catabolism - larger molecules are broken down into smaller ones in a process that usually releases energy • Anabolism - larger molecules are made from small ones in a process the usually requires energy View the Metabolic Chart
Overview of Metabolism • One of the common links between catabolism and anabolism is ATP. • ATP is used to shuttle chemical energy from catabolism to anabolism.
Overview of Metabolism • One of the common links between catabolism and anabolism is ATP. • ATP is used to shuttle chemical energy from catabolism to anabolism.
Overview of Metabolism • This is done by coupling the spontaneous reactions in catabolism to the phosphorylation of ADP to produce ATP: • And then coupling the unfavorable reactions in anabolism to the hydrolysis of ATP:
B is reduced A is oxidized Overview of Metabolism • The biological oxidation/reduction agents NAD+ and FAD are also used to shuttle energy from the favorable oxidations that take place in catabolism, to the unfavorable reductions that take place in anabolism catabolism anabolism
Overview of Metabolism • Catabolism • Occurs in stages. • Occupies the center of the metabolic chart.
Overview of Metabolism • The reactions from Acetyl-Co and below require molecular oxygen (O2). • These reactions take place in a specialized organelle called the mitochondria.
Digestion • Digestion is the first stage of metaboism in which large molecule are broken done in small molecules that can be absorbed into the blood in the small intestine. • Most of these reactions are hydrolysis reactions • Proteins are hydrolyzed in to amino acids • Polysaccharides are hydrolyzed into monosaccharides • Triglycerides are hydrolyzed into fatty acids and glycerol.
Glycolysis • Glycolysis is a series of 10 coupled reactions • The pathway starts with glucose that comes into a cell from the blood and is immediately phosphorylated to glucose-6-phosphate. • The phosphorylation traps the glucose in the cell. • The pathway then goes on to split (lyse) the the 6-carbon glucose molecule into two 3-carbon molecules and to oxidize these to α-keto acids (Pyruvic acid). • The energy released in the pathway is used to produce two types of energy rich molecules: • Two molecules of ADP are phosphorylated to ATP. • Two molecules of NAD+ are reduced to NADH/H+.
Glycolysis • Step 1: Glucose is brought into the cell and phosphorylated. • The phosphorylation is coupled to the hydrolysis of ATP.
Glycolysis • Step 2: Glucose-6-phosphate (an aldohexose) is isomerized to fructose-6-phosphate (a ketohexose). • This reaction occurs near equilibrium, which allows it to go in either direction.
Glycolysis • Step 3: Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate. • This reaction is coupled to the hydrolysis of ATP. • This sets things up for the cleavage, which occurs in the next step. • So far 2 ATP’s have been used instead of produced.
Glycolysis • Step 4: Fructose-1,6-bisphosphate splits into two three carbon monosaccharides • Glyceraldehyde-3-phophate. • Dihydroxyacetone phosphate
Glycolysis • Step 5: Dihydroxyacetone phosphate is isomerized to glyceraldehyde-3-phosphate. • The last five reactions in glycolysis start with glyceraldehyde-phosphate. • The remaing reactions will couple the oxidation of glyceraldhyde-3-phosphate to the production of ATP and NADH/H+.
Glycolysis • Step 6: Glyceraldehyde-3-phosphate is oxidized to 1,3-Bisphosphoglycerate. • The oxidation of the aldehyde to an acid is coupled to the reduction of NAD+ to NADH/H+ and the phosphorylation of the acid to a mixed phosphate anhydride. • The hydrolysis of a phosphate anhydride has a large negative ΔG.
Glycolysis • Step 7: The hydrolysis of the phosphate from 1,3-bisphosphoglycerate is coupled to the phosphorylation of ADP to generate ATP • Since two 1,3-bisphosphoglycerates are produced per glucose molecule, the two ATP’s that were invested in the first part of glycolysis have now been recovered.
Glycolysis • The remaining three steps will convert the phosphate ester in 3-phosphoglycerate into a phosphate whose hydrolysis can be coupled to the phosphorylation of ADP to produce ATP. • Phosphate esters do not have a large enough negative ΔG to be coupled to the phosphorylation of ADP.
Glycolysis • Step 8: 3-Phosphoglycerate is isomerized to 2-phosphoglycerate. • The phosphate ester is moved form carbon 3 to carbon 2. • Like most isomerization reactions, this reaction can go in either direction.
Glycolysis • Step 9: 2-Phosphoglycerate is dehydrated to form phosphoenolpyruvate. • The dehydration of the alcohol produces a double bond between carbons 2 and 3. • This produces a phosphate with a large negative free energy for hydrolysis, which can now be coupled to the phosphorylation of ADP.
Glycolysis • Step 10: The hydrolysis of the phosphate from phosphoenolpyruvate is coupled to the phosphorylation of ADP. • The hydroxyl group that is produced next to the carbon-carbon double-bond spontaneously isomerizes to a ketone.
Glycolysis • The net reaction for coupling all ten steps in glycolysis: • The energy released in the pathway is used to produce two types of energy rich molecules: • Two molecules of ADP are phosphorylated to ATP. • Two molecules of NAD+ are reduced to NADH/H+.
Glycolysis • Fates of pyruvate when molecular oxygen cannot be used to reoxidize the NADH/H+ back to NAD+. • The fermentation pathways provide away of reoxidizing NADH/H+ back to NAD+, so that it can be used to keep glycolysis going.
Gluconeogenesis • Gluconeogenesis is the synthesis of glucose from pyruvate • It uses 7 out of the 10 reactions from glycolysis. • The remaining three have too large a negative free energy to be reversed. • These include steps • 1, 3 and 10 • Alternative reactions are used to get around these falls.
Glycogen Metabolism • When glucose is not needed to meet energy needs, it can be stored as the polysaccharide glycogen and used for future energy needs. • The liver and the muscles are where glycogen is synthesized and stored. • The muscles store it for future muscular activity. • The liver stores it to help regulate blood glucose levels.
Citric Acid Cycle • If an organism can utilize molecular oxygen to accept electrons from the reduced nucleotides NADH/H+ and FADH2, then the pyruvate from glycolysis can be completely oxidized to CO2 and H2O. • These reactions occur within a cellular organelle called the mitochondria. • The first step in the complete oxidation is the decarboxylation of pyruvate to produce Acetyl-S-CoA.
Citric Acid Cycle • The Acetyl-CoA is fed into the citric acid cycle, where its two carbons are oxidized to CO2. • In the process • 3 more NAD+ are reduced to NADH/H+ • 1 FAD is reduced to FADH2 • 1 GDP is phosphorylated to GTP
Citric Acid Cycle • The net reaction for coupling all 8 steps in glycolysis:
Electron Transport Chain andOxidative Phosphorylatioin • The reoxidation of the NADH/H+ to NAD+ and FADH2 to FAD using molecular oxygen (O2) as the oxidizing agent, is carried out by the electron transport chain. • The electron transport chain is located within the inner membrane of mitochondria.
Electron Transport Chain andOxidative Phosphorylatioin • The reoxidation of the NADH/H+ to NAD+ and FADH2 to FAD using molecular oxygen (O2) as the oxidizing agent, is carried out by the electron transport chain. • The energy released in the reoxidation is coupled to the synthesis of ATP from ADP and Pi by the enzyme ATP synthase. • The coupling involves the creation of a hydrogen ion concentration gradient across the inner mitochondrial membrane. • The energy for synthesizing the ATP comes from allowing the the hydrogen ions to flow back across the membrane.
