Chapter 18: Metabolic Pathways and Energy Production

18.1: Metabolism

• Metabolism: All the chemical reactions that provide energy and the substances required for continued cell growth.

• Catabolic Reactions: These are complex molecules that are broken down into simpler ones with an accompanying release of energy.

• Anabolic Reactions: These utilize the energy available in the cell to build large molecules from simple ones.

• Adenosine Triphosphate (ATP): A high-energy compound that stores energy in the cells. It consists of adenine, a ribose sugar, and three phosphate groups.

  

Cell Structure for Metabolism

• Cell membrane: It separates the contents of a cell from the external environment and contains structures that communicate with other cells.

• Cytoplasm: It consists of the cellular contents between the cell membrane and nucleus.

• Cytosol: It is the fluid part of the cytoplasm that contains enzymes for many of the cell’s chemical reactions.

• Endoplasmic reticulum: It is the rough type that processes proteins for secretion and synthesizes phospholipids; smooth type synthesizes fats and steroids.

• Golgi complex: It modifies and secretes proteins from the endoplasmic reticulum and synthesizes cell membranes.

• Lysosome: It contains hydrolytic enzymes that digest and recycle old cell structures.

• Mitochondrion: It contains the structures for the synthesis of ATP from energy-producing reactions.

• Nucleus: It contains genetic information for the replication of DNA and the synthesis of protein.

• Ribosome: It is the site of protein synthesis using mRNA templates.

  

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Three Stages of Catabolism

1. Catabolism begins with the processes of digestion in which enzymes in the digestive tract break down large molecules into smaller ones.

   • The polysaccharides break down to monosaccharides, fats break down to glycerol and fatty acids, and the proteins yield amino acids.
   • These digestion products diffuse into the bloodstream for transport to cells.

2. Within the cells, catabolic reactions continue as the digestion products are broken down further to yield two- and three-carbon compounds.

3. The major production of energy takes place in the mitochondria, as the two-carbon acetyl group is oxidized in the citric acid cycle.

   • As long as the cells have oxygen, the hydrogen ions and electrons from the reduced coenzymes are transferred to electron transport to synthesize ATP.

     

18.2: Digestion of Foods

Digestion of Carbohydrates

• Enzymes produced in the salivary glands hydrolyze some of the 𝜶-glycosidic bods in amylose and amylopectin, producing maltose, glucose, and dextrins — which contain three to eight glucose units.

• After swallowing, the partially digested starches enter the acidic environment of the stomach, where the low pH stops carbohydrate digestion.

• In the small intestine, which has a pH of about 8, enzymes produced in the pancreas hydrolyze the remaining dextrins to maltose and glucose.

• Then enzymes produced in the mucosal cells that line the small intestine hydrolyze maltose as well as lactose and sucrose.

• The resulting monosaccharides are absorbed through the intestinal wall into the bloodstream, which carries them to the liver, where the hexose fructose and galactose are converted to glucose.

• Glucose is the primary energy source for muscle contractions, red blood cells, and the brain.

  

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Digestion of Fats

• It begins in the small intestine when the hydrophobic fat globules mix with bile salts released from the gallbladder.

• Emulsification: A process where the bile salts break the fat globules into micelles.

• Enzymes from the pancreas hydrolyze the triacylglycerols to yield monoacylglycerols and fatty acids, which are then absorbed into the intestinal lining where they recombine to form triacylglycerols.

• Chylomicrons: The nonpolar compounds are then coated with proteins to form lipoproteins which are more polar and soluble in the aqueous environment of the lymph and bloodstream.

  

Digestion of Proteins

• It begins in the stomach, where hydrochloric acid at pH 2 denatures the proteins and activates enzymes.

• Polypeptides move out of the stomach into the small intestine, where trypsin and chymotrypsin complete the hydrolysis of the peptides to amino acids.

• The amino acids are absorbed through the intestinal walls into the bloodstream for transport to the cells.

  

18.3: Coenzymes in Metabolic Pathways

• Oxidation: A reaction that involves the loss of hydrogen or electrons by a substance, or an increase in the number of bonds to oxygen.

• Reduction: A reaction that involves the gain of hydrogen ions and electrons or a decrease in the number of bonds to oxygen.

• Nicotinamide adenine dinucleotide (NAD+)

  • An important coenzyme in which the vitamin niacin provides the nicotinamide group, which is bonded to ribose and ADP.

  • The oxidized NAD+ undergoes reduction when carbon in the nicotinamide ring reacts with 2H, leaving one H+.

  • The NAD+ coenzyme is required for metabolic reactions that produce carbon–oxygen double bonds.

    

• Flavin adenine dinucleotide (FAD)

  • A coenzyme that contains ADP and riboflavin.

  • Riboflavin: Also known as Vitamin B2, consists of ribitol and flavin.

  • The oxidized form of FAD undergoes reduction when the two nitrogen atoms in the flavin part of the FAD coenzyme react with 2H reducing FAD to FADH2.

  • It is used as a coenzyme when an oxidation reaction converts a carbon–carbon single bond to a carbon–carbon double bond.

    

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• Coenzyme A

  • Its function is to prepare small acyl groups for reactions with enzymes.

  • The reactive feature of coenzyme A is the thiol group which bonds to a two-carbon acetyl group to produce the energy-rich thioester acetyl-CoA.

    

18.4: Glycolysis: Oxidation of Glucose

• Glycolysis

  • A pathway wherein the glucose in the bloodstream enters our cells where it undergoes degradation.

  • It is an anaerobic process; no oxygen is required.

  • A six-carbon glucose molecule is broken down to two molecules of three-carbon pyruvate.

  • All the reactions in glycolysis take place in the cytoplasm of the cell.

  • Energy-investing phase: The energy is obtained from the hydrolysis of two ATP, which is needed to form sugar phosphates; the first five reactions.

  • In reactions 4 and 5, a six-carbon sugar phosphate is split to yield two molecules of three-carbon sugar phosphate.

  • Energy-generating phase: The energy is obtained from the hydrolysis of the energy-rich phosphate compounds and used to synthesize four ATP; the last five reactions (6-10).

    

Energy-Investing Reactions 1 to 5

• Reaction 1: Phosphorylation
  • In the initial reaction, a phosphate group from ATP is added to glucose to form glucose6-phosphate and ADP.
• Reaction 2: Isomerization
  • The glucose-6-phosphate, the aldose from reaction 1, undergoes isomerization to fructose6-phosphate, which is a ketose.
• Reaction 3: Phosphorylation
  • The hydrolysis of another ATP provides a second phosphate group, which converts fructose-6-phosphate to fructose-1,6-bisphosphate.
• Reaction 4: Cleavage
  • Fructose-1,6-bisphosphate is split into two three-carbon phosphate isomers: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
• Reaction 5: Isomerization
  • Because dihydroxyacetone phosphate is a ketone, it cannot react further. However, it undergoes isomerization to provide a second molecule of glyceraldehyde-3-phosphate, which can be oxidized.

Energy-Generating Reactions 6 to 10

• Reaction 6: Oxidation and Phosphorylation
  • The aldehyde group of each glyceraldehyde-3-phosphate is oxidized to a carboxyl group by the coenzyme NAD+, which is reduced to NADH and H+.
  • A phosphate group adds to each of the new carboxyl groups to form two molecules of the high-energy compound, 1,3-bisphosphoglycerate.
• Reaction 7: Phosphate Transfer
  • Phosphorylation transfers a phosphate group from each 1,3-bisphosphoglycerate to ADP to produce two molecules of the high-energy compound ATP.
  • At this point in glycolysis, two ATP are produced, which balance the two ATP consumed in reactions 1 and 3.
• Reaction 8: Isomerization
  • Two 3-phosphoglycerate molecules undergo isomerization, which moves the phosphate group from carbon 3 to carbon 2 yielding two molecules of 2-phosphoglycerate.
• Reaction 9: Dehydration
  • Each of the phosphoglycerate molecules undergoes dehydration 1loss of water2 to give two high-energy molecules of phosphoenolpyruvate.
• Reaction 10: Phosphate Transfer
  • In a second direct phosphorylation, phosphate groups from two phosphoenolpyruvate are transferred to two ADPs to form two pyruvate and two ATP.

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Pathways for Pyruvate

• The pyruvate produced from glucose can now enter pathways that continue to extract energy.
• Aerobic Conditions
  • In glycolysis, two ATP were generated when one glucose molecule was converted to two pyruvates.
  • Under these conditions, pyruvate moves from the cytoplasm into the mitochondria to be oxidized further.
  • In a complex reaction, pyruvate is oxidized, and a carbon atom is removed from pyruvate as CO2.
  • The coenzyme NAD+ is reduced during oxidation.
  • The resulting two-carbon acetyl compound is attached to CoA, producing acetyl-CoA, an important intermediate in many metabolic pathways
• Anaerobic Conditions
  • When we engage in strenuous exercise, the oxygen stored in our muscle cells is quickly depleted.
  • Under these conditions, pyruvate remains in the cytoplasm where it is reduced to lactate.
  • NAD+ is produced and is used to oxidize more glyceraldehyde3-phosphate in the glycolysis pathway, which produces a small but needed amount of ATP.

18.5: The Citric Acid Cycle

• Citric Acid Cycle: A series of reactions connects the intermediate acetyl-CoA from the metabolic pathways in stages 1 and 2 with electron transport and the synthesis of ATP in stage 3.

  • It is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle.

• Citric Acid: A tricarboxylic acid, forms in the first reaction.

  

The Cycle

• Reaction 1: Formation of Citrate
  • In the first reaction of the citric acid cycle, the acetyl group from acetyl-CoA bonds with oxaloacetate to yield citrate.
• Reaction 2: Isomerization
  • The citrate produced in reaction 1 contains a tertiary alcohol group that cannot be oxidized further
  • The citrate undergoes isomerization to yield its isomer isocitrate, which provides a secondary alcohol group that can be oxidized in the next reaction.
• Reaction 3: Oxidation and Decarboxylation
  • The secondary alcohol group in isocitrate is oxidized to a ketone.
  • A decarboxylation converts a carboxylate group to a CO2 molecule producing 𝜶-ketoglutarate.
  • The oxidation reaction also produces hydrogen ions and electrons that reduce NAD+ to NADH and H+.
  • This reduced coenzyme NADH will be important in the energy-producing reactions we will discuss in electron transport
• Reaction 4: Oxidation and Decarboxylation
  • 𝜶-ketoglutarate undergoes oxidation and decarboxylation to produce a four-carbon group that combines with CoA to form succinyl-CoA
• Reaction 5: Hydrolysis
  • Succinyl-CoA undergoes hydrolysis to succinate and CoA. The energy released is used to add a phosphate group to GDP which yields GTP.
• Reaction 6: Oxidation
  • Hydrogen is removed from each of two carbon atoms in succinate, which produces fumarate, a compound with a trans double bond.
• Reaction 7: Hydration
  • Hydration adds water to the double bond of fumarate to yield malate, which is a secondary alcohol.
• Reaction 8: Oxidation
  • The last step of the citric acid cycle, the secondary alcohol group in malate is oxidized to oxaloacetate, which has a ketone group.

18.6: Electron Transport and Oxidative Phosphorylation

• In electron transport, hydrogen ions and electrons from NADH and FADH2 are passed from one electron carrier to the next until they combine with oxygen to form H2O.

  

• Oxidative phosphorylation: The energy released during electron transport is used to synthesize ATP from ADP and Pi.

  • Chemiosmotic model: Links the energy from electron transport to a H+ gradient that drives the synthesis of ATP.

• ATP Synthesis: An enzyme complex that uses the energy released by H+ ions returning to the matrix to synthesize ATP from ADP and Pi .

• ATP from Glycolysis

  • In glycolysis, the oxidation of glucose stores energy in two NADH molecules as well as two ATP from direct phosphate transfer.
  • However, glycolysis occurs in the cytoplasm, and the NADH produced cannot pass through the mitochondrial membrane.

• ATP from the Oxidation of Two Pyruvate

  • Under aerobic conditions, pyruvate enters the mitochondria, where it is oxidized to give acetyl-CoA, CO2, and NADH.
  • Because glucose yields two pyruvates, two NADH enter electron transport, where the oxidation of two pyruvate leads to the production of six ATP.

• ATP from the Citric Acid Cycle: One turn of the citric acid cycle produces two CO2, three NADH, one FADH2, and one ATP by direct phosphate transfer.

• ATP from the Complete Oxidation of Glucose: The total ATP for the complete oxidation of glucose is calculated by combining the ATP produced from glycolysis, the oxidation of pyruvate, and the citric acid cycle.

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18.7: Oxidation of Fatty Acids

• A large amount of energy is obtained when fatty acids undergo oxidation in the mitochondria to yield acetyl-CoA.

• Beta-oxidation: This is where fatty acids undergo the removal of two-carbon segments, one at a time, from the carboxyl end.

  

• Fatty Acid Activation: It combines fatty acid with coenzyme A to yield fatty acyl-CoA.

  • The energy for the activation is obtained from the hydrolysis of ATP to give AMP and two inorganic phosphates.

    

• Ketone Bodies: The products of ketogenesis: are acetoacetate, 𝜷-hydroxybutyrate, and acetone.

• Ketosis: A condition of the accumulation of ketone bodies; which occurs in severe diabetes, diets high in fat and low in carbohydrates, alcoholism, and starvation.

18.8: Degradation of Amino Acids

• Transamination

  • An 𝜶-amino group is transferred from an amino acid to an a-keto acid, usually a-ketoglutarate.

  • A new amino acid and a new 𝜶-keto acid.

    

• Oxidative Deamination: The ammonium group in glutamate is removed as an ammonium ion.

  

• Urea Cycle: A series of reactions that detoxifies ammonium ions by forming urea.

  • The ammonium ion, which is the end product of amino acid degradation, is toxic if it is allowed to accumulate.

    

  

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