CATABOLISM

• Carbohydrates, fats, and proteins must be hydrolyzed into small molecules that can be absorbed through the intestinal walls before they can be used for energy or to build compounds needed by the body
• Carbohydrate metabolism


  1. Complex carbohydrates (di- and polysaccharides) are broken down by enzymes and stomach acid to produce monosaccharides, the most important of which is glucose

  2. Glucose can be used to build new oligo- and polysaccharides or to provide energy through the process of glycolysis

  
• Lipid metabolism


  1. Ingested fats are hydrolyzed by lipases to glycerol and fatty acids or to monoglycerides, which are absorbed through the intestine

  2. These smaller molecules can be used to build complex molecules needed in membranes, oxidized to provide energy, or stored in fat storage depots

  3. The specific pathway used by cells to obtain energy from fatty acids is called beta-oxidation

  
• Protein metabolism


  1. Proteins are hydrolyzed by HCl in the stomach and by digestive enzymes in the stomach and intestines to produce their constituent amino acids

  2. The amino acids absorbed through the intestinal wall enter the amino acid pool and serve as building blocks for proteins as needed or, to a smaller extent, as a fuel for energy
• The nitrogen of the amino acids is catabolized through oxidative deamination and the urea cycle and is expelled from the body as urea in the urine
• Glycolysis


  1. A series of 10 enzyme-catalyzed reactions by which glucose is oxidized to two molecules of pyruvate

  2. During glycolysis, there is net conversion of 2 ADP to 2 ATP

  
• Hexokinase (HK)


  Enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate

  
• Phosphoglucoisomerase (PGI)


  Enzyme that catalyzes the isomerization of glucose-6-phosphate to fructose-6-phosphate

  
• Phosphofructokinase-1 (PFK-1)


  Enzyme that catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate
• Aldolase


  Enzyme that catalyzes the cleavage of fructose-1,6-bisphosphate into two triose phosphates: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate

  
• Triose Phosphate Isomerase (TPI)


  Enzyme that catalyzes the interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate

  
• Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)


  Enzyme that catalyzes the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate

  
• Phosphoglycerate Kinase (PGK)


  Enzyme that catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
• Phosphoglycerate Mutase (PGM)


  Enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate

  
• Enolase


  Enzyme that catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate (PEP)
• Pyruvate Kinase (PK)


  Enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, forming ATP and pyruvate

  
• The net equation for glycolysis is: C6H12O6 + 2NAD+ + 2HPO4^2- + 2ADP → 2CH3CCOO- + 2NADH + 2ATP + 2H2O + 2H+

  
• Reactions of pyruvate


  Pyruvate is most commonly metabolized in one of three ways: 1) converted to ethanol under anaerobic conditions in yeast, 2) converted to lactate under anaerobic conditions in contracting muscle, or 3) converted to acetyl CoA and then metabolized through the citric acid cycle under aerobic conditions in plants and animals
• Glycolysis


  Glucose + 2NAD+ + 2HPO4^2- + 2ADP → 2 Pyruvate + 2NADH + 2ATP + 2H2O + 2H+

  
• Pyruvate


  Final product of glycolysis

  
• Pyruvate metabolism


  1. Pyruvate → Ethanol + CO2

  2. Pyruvate → Lactate
• Glycolysis reactions occur in the cytoplasm outside the mitochondria
• Pyruvate does not accumulate in the body
• In certain bacteria and yeast, pyruvate undergoes decarboxylation followed by reduction to produce ethanol
• Pyruvate reduction


  Pyruvate + NADH + H+ → Lactate + NAD

  
• In cancer cells, pyruvate is primarily converted to lactate
• In normal cells that carry out aerobic metabolism, pyruvate enters the citric acid cycle

  
• Glycolysis needs a continuing supply of NAD+
• If no oxygen is present to reoxidize NADH to NAD+, another way must be found to reoxidize it
• Glycolysis


  C6H12O6 + 2NAD+ + 2HPO4^2- + 2ADP → 2 Pyruvate + 2NADH + 2ATP + 2H2O + 2H+

  
• Pyruvate oxidative decarboxylation


  Pyruvate → Acetyl CoA + CO2
• Pyruvate is not the end product of aerobic glucose metabolism

  
• Pyruvate undergoes oxidative decarboxylation to form acetyl CoA, which provides entrance to the citric acid cycle

  
• In glycolysis, two ATPs are produced from the anaerobic portion of the pathway leading to pyruvate

  
• Glucose-6-phosphate


  Central role in several different entries into the glycolytic pathway

  
• Pentose phosphate pathway


  Pathway that has the capacity to produce NADPH and ribose as well as energy
• NADPH


  • Needed in many biosynthetic processes, including synthesis of unsaturated fatty acids, cholesterol, and amino acids as well as photosynthesis and the reduction of ribose to deoxyribose for DNA
• Ribose


  • Needed for the synthesis of RNA
• When the body needs synthetic ingredients more than energy, glucose-6-phosphate is used in the pentose phosphate pathway

  
• When energy is needed, glucose-6-phosphate remains in the glycolytic pathway