SECTION A: PROTEIN BINDING SITES

1. BINDING-SITE CHARACTERISTICS
   1. Ligands bind to proteins at sites that have shapes that are complementary to the ligand shape.
   2. Protein binding sites have the properties of chemical specificity, affinity, saturation, and competition.

2. REGULATION OF BINDING-SITE CHARACTERISTICS
   1. Protein activity in a cell can be controlled by regulating either the shape of the protein or the amounts of protein synthesized and degraded.
   2. The binding of a modulator molecule to the regulatory site on an allosteric protein alters the shape of the functional binding site, thereby altering its binding characteristics and the activity of the protein. The activity of allosteric proteins is regulated by varying the concentrations of their modulator molecules.
   3. Protein kinase enzymes catalyze the addition of a phosphate group to the side chains of certain amino acids in a protein, changing the shape of the protein's binding site and thus altering the protein's activity by covalent modulation. A second enzyme is required to remove the phosphate group, returning the protein to its original state.

3. ENZYMES AND CHEMICAL ENERGY
   1. In adults the rates at which organic molecules are continuously synthesized (anabolism) and broken down (catabolism) are approximately equal.

SECTION B: ENZYMES AND CHEMICAL ENERGY

1. CHEMICAL REACTIONS
   1. The difference in the energy content of reactants and products is the amount of energy(measured in calories) that is released or added during a reaction.
   2. The energy released during a chemical reaction either is released as heat or is transferred to other molecules.
   3. The four factors that can alter the rate of a chemical reaction are (1) reactant concentrations, (2) activation energy, (3) temperature, and (4) catalysts.
   4. The activation energy required to initiate the breaking of chemical bonds in a reaction is usually acquired through collisions with other molecules.
   5. Catalysts increase the rate of a reaction by lowering the activation energy.
   6. The characteristics of reversible and irreversible reactions at chemical equilibrium are (1) product concentrations are only slightly higher than reactant concentrations, and (2) almost all reactant molecules have been converted to product, respectively .
   7. The net direction in which a reaction proceeds can be altered, according to the law of mass action, by increases or decreases in the concentrations of reactants or products.

2. ENZYMES
   1. Nearly all chemical reactions in the body are catalyzed by enzymes, the characteristics o: which are that enzymes (1) have no net chemical change from a reaction, (2) bind like ligands, (3) increase rates of reactions but do not cause reactions to occur that otherwise would not, (4) lower activation energy but do not alter net energy added or released by reactants
   2. Some enzymes require small concentrations of cofactors for activity.
      1. The binding of trace metal cofactors maintains the conformation of the enzyme's binding site so that it is able to bind substrate.
      2. Coenzymes, derived from vitamins, transfer small groups of atoms from one substrate to another. The coenzyme is regenerated in the course of these reactions and can be used over and over again.

3. REGULATION OF ENZYME-MEDIATED REACTIONS
   1. The rates of enzyme-mediated reactions can be altered by changes in temperature, substrate concentration, enzyme concentration, and enzyme activity. Enzyme activity is altered by allosteric or covalent modulation.

4. MULTIENZYME METABOLIC PATHWAYS
   1. The rate of product formation in a metabolic pathway can be controlled by allosteric or covalent modulation of the enzyme mediating the rate-limiting reaction in the pathway. The end product often acts as a modulator molecule, inhibiting the rate-limiting enzyme's activity.
   2. An "irreversible" step in a metabolic pathway can be reversed by the use of two enzymes, one for the forward reaction and one for the reverse direction via another, energy-yielding reaction.

5. ATP
   1. In all cells, energy is transferred from the catabolism of fuel molecules to ATP. The hydrolysis of ATP to ADP then transfers this energy to cell functions. ATP is formed by substrate level phosphorylation and oxidative phosphorylation.

SECTION C: METABOLIC PATHWAYS

1. CELLULAR ENERGY TRANSFER
   1. The end products of glycolysis under aerobic conditions are ATP and pyruvate, whereas ATP and lactate are the end products under anaerobic conditions.
      1. Carbohydrates are the only fuel molecules that can enter the glycolytic pathway, enzymesfor which are located in the cytosol.
      2. During anaerobic glycolysis, hydrogen atoms are transferred to NAD, which then transfers them to pyruvate to form lactate, thus regenerating the original coenzyme molecule.
      3. During aerobic glycolysis, NADH + H transfers its hydrogen atoms to the oxidative phosphorylation pathway.
      4. The formation of ATP in glycolysis is by substrate level phosphorylation, a process in which a phosphate group is transferred from a phosphorylated metabolic intermediate directly to ADP.

   2. The Krebs cycle, the enzymes of which are in the matrix of the mitochondria, catabolizes molecular fragments derived from fuel molecules and produces carbon dioxide, hydrogen atoms, and ATP.
      1. Acetyl coenzyme A, the acetyl portion of which is derived from all three types of fuelmolecules, is the major substrate entering the Krebs cycle. Amino acids can also enter at several other sites in the cycle by being converted to cycle intermediates.
      2. During one rotation of the Krebs cycle two molecules of carbon dioxide are produced, and four pairs of hydrogen atoms are transferred to coenzymes. By substrate level phosphorylation one molecule of GTP is formed, which can be converted to ATP.

   3. Oxidative phosphorylation forms ATP from ADP and , using the energy released when molecular oxygen ultimately combines with hydrogen atoms to form water.
      1. The enzymes for oxidative phosphorylation are located on the inner membrane of mitochondria.
      2. Hydrogen atoms derived from glycolysis, the Krebs cycle, and the breakdown of fatty acids are delivered to the electron transport chain, which regenerates the hydrogen-free forms of the coenzymes NADand FAD by transferring the hydrogens to molecular oxygen to form water.
      3. The reactions of the electron transport chain produce a hydrogen ion gradient across the inner mitochondrial membrane. Hydrogen ion flow back across the membrane provides the energy for ATP synthesis.
      4. Small amounts of reactive oxygen species, which can damage proteins, lipids and nucleic acids, are formed during electron transport.

2. CARBOHYDRATE, FAT AND PROTEIN METABOLISM
   1. The aerobic catabolism of carbohydrates proceeds through the glycolytic pathway to pyruvate, which enters the Krebs cycle and is broken down to carbon dioxide.
      1. About 40 percent of the chemical energy in glucose can be transferred to ATP under aerobic conditions, the rest appearing as heat.
      2. Under aerobic conditions, 38 molecules of ATP can be formed from 1 molecule of glucose: 34 from oxidative phosphorylation, 2 from glycolysis, and 2 from the Krebs cycle.
      3. Under anaerobic conditions, 2 molecules of ATP are formed from 1 molecule of glucose during glycolysis.

   2. Carbohydrates are stored as glycogen, primarily in the liver and skeletal muscles.
      1. Two different enzymes are used to synthesize and break down glycogen. The control of these enzymes regulates the flow of glucose to and from glycogen.
      2. In most cells glucose 6-phosphate is formed by glycogen breakdown and is catabolized to produce ATP. In liver and kidney cells, glucose can be derived from glycogen and released from the cells into the blood.

   3. New glucose can be synthesized (gluconeogenesis) from some amino acids, lactate, and glycerol via the enzymes that catalyze reversible reactions in the glycolytic pathway. Fatty acids cannot be used to synthesize glucose.
   4. Fat, stored primarily in adipose tissue, provides about 80 percent of the stored energy in the body.
      1. Fatty acids are broken down, two carbon atoms at a time, in the mitochondrial inner compartment by beta oxidation, to form acetyl coenzyme A and hydrogen atoms, which combine with coenzymes.
      2. The acetyl portion of acetyl coenzyme A is catabolized to carbon dioxide in the Krebs cycle, and the hydrogen atoms generated there plus those generated during beta oxidation are used by the oxidative phosphorylation pathway to form ATP.
      3. The amount of ATP formed by the catabolism of 1 g of fat is about 2 1/2 times greater than the amount formed from 1 g of carbohydrate.
      4. Fatty acids are synthesized from acetyl coenzyme A by enzymes in the cytosol and are linked to -glycerol phosphate, produced from carbohydrates, to form triacylglycerols by enzymes in the smooth endoplasmic reticulum.

   5. Proteins are broken down to free amino acids by proteases.
      1. The amino groups of amino acids are removed, forming keto acids, which can either be catabolized via the Krebs cycle to provide energy for the synthesis of ATP or be converted into glucose and fatty acids.
      2. Amino groups are removed by
         1. oxidative deamination, which gives rise to ammonia, or by
         2. transamination, in which the amino group is transferred to a keto acid to form a new amino acid.

      3. The ammonia formed from the oxidative deamination of amino acids is converted to urea by enzymes in the liver and then excreted in the urine by the kidneys.

   6. Some amino acids can be synthesized from keto acids derived from glucose, whereas others cannot be synthesized by the body and must be provided in the diet.

3. ESSENTIAL NUTRIENTS
   1. Approximately 50 essential nutrients are necessary for health but cannot be synthesized in adequate amounts by the body and must therefore be provided in the diet.
   2. A large intake of water-soluble vitamins leads to their rapid excretion in the urine, whereas large intakes of fat-soluble vitamins lead to their accumulation in adipose tissue and may produce toxic effects.