Lecture Notes on Completing Oxidation of Glucose and Anabolism

Completing Oxidation of Glucose/Other Carbohydrates/Anabolism from Catabolic Products

Products of Cellular Respiration after Glycolysis

• If a final electron acceptor is present, the complete oxidation of pyruvate occurs in the matrix of the mitochondria.

• Captured electrons are used to create a proton gradient.

• Before further oxidation, pyruvate must cross two lipid bilayers into the matrix of the mitochondria.

• Electrons captured from glycolysis may also enter the mitochondrial matrix.

Mitochondria Structure

• In eukaryotes, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation take place in mitochondria.

Transport of Pyruvate and NADH

• The outer membrane of mitochondria has nonselective channels (pores) which allow free access of pyruvate and NADH.

• The inner membrane has specific transporters for pyruvate.

• NADH does not pass through the membrane but donates electrons to a substrate which is transported through the inner membrane and reoxidized in the matrix of the mitochondria.

• The electrons are donated to $NAD^+$ or $FAD$.

Oxidation of Pyruvate to AcetylCoA

• The reaction is an oxidative decarboxylation of pyruvate and attachment of the cofactor, CoA, to the remaining carbons of pyruvate.

• It is a coupled reaction that utilizes the energy released by oxidation (exergonic) to the attachment of CoA to the remaining two-carbon fragment (acetyl) of pyruvate (endergonic).

• There was a similar coupling by triose phosphate dehydrogenase in glycolysis sans decarboxylation.

• There are two similar reactions in the citric acid cycle.

• All these steps are accomplished by a huge multienzyme complex, pyruvate dehydrogenase, which contains the vitamins thiamine and lipoic acid.

Acetyl CoA Synthesis

• Mechanism of Pyruvate Dehydrogenase

Structure of Acetyl-CoA

• Oxidized carboxyl (COOH) group is removed and released as CO2 (decarboxylation)

• The remain 2 carbon fragments is oxidized to acetate and extract electrons are passsed to NAD+ (redox)

• CoA is attached to the acetate by a hight energy bond ( activation using redox energy)

Products of Cellular Respiration after Pyruvate Oxidation

• The citric acid cycle (CAC) has eight steps, each catalyzed by a specific enzyme.

• The acetyl group (2 carbons) of acetyl CoA joins the cycle by combining with oxaloacetate (4 carbons), forming citrate (6 carbons) catalyzed by citrate synthase.

• The next seven steps oxidatively decompose the citrate back to oxaloacetate, making the process a cycle with the loss of two carbons per acetyl group.

• The four carbons added to the CAC from 2 acetyl are released as $CO_2$ completing the oxidation of the original glucose.

Thermodynamics of the Reactions of the Citric Acid Cycle

Products of Cellular Respiration after Citric Acid Cycle

• Oxidative Phosphorylation

  • The creation of a proton ($H^+$) gradient by the electron transport chain.

  • The energy in the proton gradient is utilized to drive ATP synthesis as the proton returns into the mitochondrial matrix through the ATP synthase complex.

Other Carbohydrates

• Polysaccharides (Macromolecules)

  • ~100 or more monosaccharides covalently joined by dehydration reactions

  • Common polysaccharides are amylose, glycogen, and cellulose. All these are polymers of glucose that differ in source or bonding difference between monosaccharides.

• Disaccharides

  • Compounds containing 2 monosaccharides covalently joined by dehydration reactions

  • Common disaccharides are sucrose, maltose, and lactose

Polysaccharides (“many sugars”)

• Macromolecules formed by the polymerization of many monosaccharide subunits (monomers)

• Two common energy storage polysaccharides:

  • Starch and glycogen

• Two common structural polysaccharides:

  • Cellulose and chitin

Storage Polymers of Glucose

• If glucose is not required by a cell it can be stored as the polysaccharides glycogen in animals or amylose and amylopectin in plants.

• The bonds covalently linking the glucose monomer are termed glycosidic bonds.

• The glycosidic bonds in all of these polysaccharides are always $\alpha$ (1->4) and in amylopectin and glycogen $\alpha$(1->6).

• The amylose can be hydrolyzed to glucose monomers by amylase.

• The glucose monomers from glycogen are accessed by phosphorolysis to give glucose-1-phosphate. A mutase converts G-1-P to G-6-P.

Monosaccharide Anomeric Isomers

• Monosaccharides with five or more carbons can change from the linear form to a ring form

Storage Polysaccharides I

• Glycogen is made by animals to store energy, usually in liver and muscle tissues.

  • Highly branched

Storage Polysaccharides II

• Starch is made by plants to store energy

  • Amylose = linear, unbranched

  • Amylopectin = branched

Structural Polymers of Glucose

• Glucose polymers can be used for structural purposes in cellulose and chitin.

• The glycosidic bonds in all of these polysaccharides are always b (1->4).

• In chitin, the 2’ position contains an aminoacetyl group.

• These b linkages are highly resistant to hydrolysis and very few organisms have the required enzymes to catalyze the reaction.

Structural Polysaccharides

• Cellulose is made by plants as a structural fiber in cell walls

  • Unbranched chain of glucoses connected by $\beta$-linkages

  • Extremely strong

Structural Polysaccharides II

• Chitin is tough and resilient, used for cell walls of fungi and exoskeletons of arthropods

  • Similar structure to cellulose, but glucose sub-units modified with nitrogen-containing groups

Enter of Fructose and Galactose into Glycolysis

• Fructose can be phosphorylated to fructose-6-phosphate and enter glycolysis.

• Galactose is converted to glucose in a reaction that requires an NTP.

Other Monosaccharides in Glycolysis

The Versatility of Catabolism

• Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration

• Glycolysis accepts a wide range of carbohydrates

• Proteins must be digested to amino acids; amino groups removed, and the remainder can feed glycolysis or the citric acid cycle

• Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)

• An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate

Cellular Respiration can have Alternate Sources of Electron Donors and Electron Acceptors

• Chemolithotrophs: The electron donors is an inorganic molecules (e.g., H2S, H2, NH4).

• Anaerobic Respiration: The final electron acceptor may be either inorganic molecules (e.g. Fe3+, CO2, SO4 -)or organic molecules (i.e. trimethylamine N-oxide, fumarate).

Biosynthesis (Anabolic Pathways)

• The body uses small molecules to build other substances

• These small molecules may come directly from food and cannot be made by the organism (i.e vitamins, essential nutrients)

• Many precursors for biosynthesis are intermediates from cellular respiration

Anabolic Precursors from Catabolism

Anabolic Products from Catabolic Products: DHAP can be Reduced to form Glycerol 3 –phosphate

Anabolic Products from Catabolic Products: Pyruvate Amidated to form L-alanine