PowerPoint Presentation to accompany Hole’s Human Anatomy and Physiology, 9/e by Shier, Butler, and Lewis

Chapter 4 Cellular Metabolism

Metabolic Processes Anabolism is the process by which large molecules are built from smaller ones. Anabolism often occurs through dehydration synthesis. Catabolism is the process by which large molecules are broken down into small ones. This often occurs through hydrolysis.

Dehydration Synthesis Joins monosaccharides to form glycogen Joins glycerol and fatty acids to form fat molecules Joins amino acids by way of a peptide bond to form dipeptides, polypeptides, and proteins

Hydrolysis Breaks down carbohydrates into monosaccharides Breaks down fats into glycerol and fatty acids Breaks down proteins into amino acids Breaks down nucleic acids into nucleotides

Enzyme Action Enzymes are globular proteins that promote chemical reactions by lowering the activation energy required to start the reaction.

Enzyme Action Enzymes are not consumed by the reaction so they are needed only in very small quantities. Enzymes are specific and act only on particular substrates.

Enzyme Action The active site of the enzyme combines with regions of the substrate, forming an enzyme- substrate complex. Figure 4.4

Enzyme Action This interaction strains the chemical bonds and makes a reaction more likely. The product and enzyme are released with no change to the active site.

Cofactors and Coenzymes Enzymes are often inactive until combining with cofactors or coenzymes. Cofactors are inorganic ions, such as copper, zinc, or iron. Coenzymes are small organic molecules that are often vitamins or derived from vitamins.

Denaturation Enzymes, like all proteins, can be denatured. A denatured protein has an altered structure and can inactivate enzymes. Proteins can be denatured by heat, radiation, certain chemicals, pH extremes.

Release of Chemical Energy Metabolism depends on chemical energy. Cellular respiration releases energy from molecules such as glucose.

Release of Chemical Energy Cellular respiration occurs in three sets of reactions: glycolysis, the citric acid cycle, and the electron transport chain (oxidative phosphorylation). Figure 4.6

Adenosine Triphosphate ATP is the energy currency of the cell. Each ATP molecule has three parts: adenine, ribose, and three phosphates.

Adenosine Triphosphate The third phosphate is attached with a high energy bond. This chemical energy can be easily transferred to other molecules in metabolic processes. Figure 4.7

Glycolysis Glycolysis occurs in the cytosol.

Glycolysis It converts a 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules. Glycolysis is anaerobic; it does not require oxygen to proceed.

Glycolysis Glucose is phosphorylated in two places, requiring ATP. The 6-carbon glucose is split into two 3- carbon pyruvic acid molecules. NADH is produced through the release of hydrogen atoms which are carried by NAD + to the electron transport chain. ATP is synthesized.

NADH, nicotinamide adenine dinucleotide, is an important e- carrier. NADH plays a key role in the production of energy through redox reactions. Remember from Chem I: Oxidation-reduction reactions remove oxygen from a substance (ergo: reduction) and redox reactions add oxygen to a substance, or burns them. NAD+ serves as a cofactor for the enzymes serving as dehydrogenases, reductases and hydroxylases, making it a major carrier of H + and e- in our study of major metabolic pathways such as glycolysis, and the Citric Acid cycle (Kreb’s or the tricarboxylic acid cycle).

Enzymes accelerate reaction rates by bringing substrates together in an optimal orientation. By setting the stage for making and breaking bonds, cofactors stabilize transitions states. Transition states are high-energy species in reaction pathways. By doing this selectively, our enzymes determine which of several potential chemical reactions occur. What does NAD do? Nicotinamide adenine dinucleotide, NAD, is one of the most important coenzymes in the cell. NAD along with a related NADP (we’ll look at later) are two of the most abundant cofactors in a cell.

Healthy bodies make all the NADH needed using Vitamin B3, known as niacin or chemically, nicotinamide, as a starting point. The NAD coenzyme acts as a hydrogen acceptor in oxidation-reduction reactions. The electron transport chain in cellular respiration is responsible for energy production and is an excellent illustration of NAD's involvement in redox reactions.The electron transport chain in cellular respiration is responsible for energy production and is an excellent illustration of NAD's involvement in redox reactions.

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Anaerobic Respiration Oxygen is the electron acceptor in the electron transport chain allowing NADH + H + to deliver electrons and replenish NAD +.. Without oxygen, NADH + H + releases H + ions and electrons to pyruvic acid, forming lactic acid. This is anaerobic metabolism.

Aerobic Respiration When oxygen is available, pyruvic acid moves from cytosol into mitochondria. Figure 4.12

Aerobic Respiration Enzymes remove H + and a carbon atom. NADH, carbon dioxide, and acetic acid are produced. Acetic acid combines with coenzyme A to form acetyl CoA.

Citric Acid Cycle 2-carbon acetyl CoA combines with 4- carbon oxaloacetic acid to form 6-carbon citric acid. Coenzyme A is released. A series of reactions regenerate oxaloacetic acid and produce ATP, NADH + H +, FADH2, and carbon dioxide. This cycle can be repeated as long as oxygen and pyruvic acid are available.

Figure 4.10

Electron Transport Chain H + ions and electrons are carried by NADH and FADH 2 and hold chemical energy. Figure 4.11

Electron Transport Chain Electrons are transferred through a series of enzyme complexes on the folds of the inner mitochondrial membrane. Electron energy is transferred to ATP. Oxygen receives the H + ions and electrons to form water.

Carbohydrate Storage Excess glucose may enter anabolic carbohydrate pathways and stored as glycogen. Figure 4.13

Carbohydrate Storage Liver and muscle store glycogen. Glucose can also be converted to fat molecules and stored in adipose tissue.

Metabolic Pathways Regulatory enzymes can determine the rate of a metabolic pathway.

Metabolic Pathways Rate-limiting enzymes are the first enzyme in a series to prevent accumulation of intermediates. Products of metabolic reactions can inhibit the rate-limiting enzyme through negative feedback.

Genetic Information The portion of the DNA molecule that contains genetic information for a particular protein is a gene. All of the DNA in a cell is its genome. The correspondence between DNA information and amino acids is the genetic code.

DNA Structure A DNA molecule consists of a double helix of two polynucleotide chains oriented antiparallel. Figure 4.19

DNA Structure Nitrogenous bases are attached to the sugar- phosphate backbone of the chains. There are four bases in DNA: adenine (A), Thymine (T), Guanine (G), Cytosine (C). These bases exhibit complementary base pairing, A pairs with T and G pairs with C.

Genetic Code Each of the twenty different amino acids is represented in the DNA molecule by a triplet code, three nucleotides. For example CGT represents one amino acid while GCA represents another. Triplets of nucleotides also provide stop and start signals for protein synthesis.

RNA Molecules RNA molecules are single strands containing the sugar ribose instead of deoxyribose. Figure 4.21

RNA Molecules The four bases of RNA are adenine (A), Guanine (G), Cytosine (C), and Uracil (U). The first step in delivery of genetic information is synthesis of messenger RNA (mRNA) in a process called transcription.

Transcription The DNA double helix unwinds in one region, exposing the gene. Figure 4.22

Transcription RNA polymerase binds to the DNA and creates a mRNA copy by matching complementary base pairs A-U and G-C. Figure 4.22

Transcription At a stop signal, the mRNA molecule is released with no change to the gene which rewinds into a double helix.

Protein Synthesis (Translation) Transfer RNA (tRNA) align amino acids in the appropriate order for peptide bonding. The three mRNA nucleotides that code for the amino acid are the codon. Figure 4.23

Protein Synthesis (Translation) The corresponding tRNA contains an anticodon. The binding of tRNA and mRNA occurs in association with a ribosome.

DNA Replication DNA replication creates an exact copy of a DNA molecule. Replication occurs during interphase. Figure 4.24

DNA Replication Hydrogen bonds between paired bases break and new nucleotides base pair.

DNA Replication DNA polymerase catalyzes the process. The resulting double helix contains one strand from the original molecule and one new complementary strand.

Changes in Genetic Information Mutations occur when DNA is damaged or replication mistakes occur. Mutations occur when a base is paired incorrectly or a base is inserted or deleted. In all cases DNA information is altered. Repair enzymes often correct mutations. Mutagens are chemicals that cause mutation.