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Chapter 1 The Cell: A Microcosm of Life 2009 Cengage-Wadsworth Cells--the essence of life • Basic units of the body • Eukaryotic cells – Have a defined nucleus – Evolved from prokaryotic cells (which don’t) • Specialization 2009 Cengage-Wadsworth Components of Typical Cells • • • • • • • • Plasma membrane Cytoplasmic matrix Mitochondrion Nucleus Endoplasmic reticulum Golgi apparatus Lysosomes Peroxisomes 2009 Cengage-Wadsworth Plasma Membrane • Sheetlike structures made of phospholipids & proteins • Have hydrophobic & hydrophylic moiety • Phospholipids = phosphoglycerides & phosphingolipids • Proteins give them their functions 2009 Cengage-Wadsworth Plasma Membrane • Asymmetrical • Fluid structures • Distinct from other membranes: – Greater CHO content – Greater cholesterol content 2009 Cengage-Wadsworth Plasma Membrane • Lipid bilayer concept • Glycocalyx • Glycoproteins • Membrane proteins – Integral – Peripheral 2009 Cengage-Wadsworth Cytoplasmic Matrix • Microtrabecular lattice or cytoskeleton – Microtubules – Microfilaments • Fluid 2009 Cengage-Wadsworth Cytoplasmic Matrix • Structural arrangement influences metabolic pathways: – Glycolysis – Hexose monophosphate shunt – Glycogenesis & glycogenolysis – Fatty acid synthesis • Communication 2009 Cengage-Wadsworth Mitochondrion • Energy production & oxygen use site • Matrix surrounded by double membrane • Mitochondrial membrane – Outer membrane - porous – Inner membrane - selectively permeable; site of electron transport chain 2009 Cengage-Wadsworth Mitochondrion • Mitochondrial matrix – Site of TCA cycle & fatty acid oxidation – Contains DNA so organelle can divide • In all cells except erythrocytes 2009 Cengage-Wadsworth Nucleus • Contains DNA (genome) • Surrounded by nuclear envelope • Nucleoli - condensed chromatin • DNA replication • Protein synthesis = transcription, translation & elongation 2009 Cengage-Wadsworth Nucleus • Nucleic acids – DNA & RNA – Consist of nucleotides or bases • Adenine, guanine, cytosine in both • Uracil in RNA only • Thymine in DNA only – Complementary base pairing 2009 Cengage-Wadsworth Nucleus • Cell replication – DNA unravels and nucleotides are added to each strand to make 2 sets • Cell transcription – mRNA created from sequence of 1 DNA strand (sense strand) – Genes – Introns - intervening sequences – Exons - no posttranslational processing 2009 Cengage-Wadsworth Nucleus • Translation – mRNA codes for amino acid sequence to form protein – mRNA is synthesized in nucleus, then moves to RER in cytoplasmic matrix – Codons - 3-base sequences that code for amino acids – tRNA bring AAs to mRNA on ribosomes 2009 Cengage-Wadsworth Nucleus – After AAs are positioned, peptide bonds form between them = elongation – “Nonsense” codon signals end of protein 2009 Cengage-Wadsworth Endoplasmic Reticulum & Golgi Apparatus • ER = network of membranous channels • Types: – Rough ER (studded with ribosomes) protein synthesis – Smooth ER - lipid synthesis – Sarcoplasmic reticulum (SER in muscle) - calcium ion pump 2009 Cengage-Wadsworth Endoplasmic Reticulum & Golgi Apparatus • Golgi apparatus – Protein trafficking & sorting – 4-8 cisternae – Tubular networks at either end: • Cis-Golgi network - entrance • Trans-Golgi network - exit – Connected to ER by transport vesicles 2009 Cengage-Wadsworth Lysosomes & Peroxisomes • Enzyme-filled organelles • Lysosomes - cell’s “digestive system” • Peroxisomes - site of oxidative catabolic reactions 2009 Cengage-Wadsworth Lysosomes & Peroxisomes • Lysosome functions: – – – – Phagocytosis Autolysis Bone resorption Hormone secretion & regulation • Peroxisome functions: – Oxidize fatty acids to acetyl CoA – Amino acid catabolism – Detoxifying reactions 2009 Cengage-Wadsworth Cellular Proteins • Types: – Receptors - modify cell’s response to environment – Transport proteins - regulate flow of materials into & out of cell – Enzymes - catalysts 2009 Cengage-Wadsworth Receptors & Intracellular Signaling • Ligands - molecular stimuli that attach to receptors • Types of receptors: – Bind to ligand & convert it to internal signal – Serve as ion channels – Internalize stimulus intact 2009 Cengage-Wadsworth Receptors & Intracellular Signaling • Internal chemical signal – E.g. 3’, 5’-cyclic adenosine monophosphate (cyclic AMP, cAMP) • Ion channel – E.g. receptor for acetylcholine • Internalization stimulus – E.g. insulin, triiodothyronine 2009 Cengage-Wadsworth Transport Proteins • May act as pumps • May provide pores through which molecules diffuse • Most studied = sodium (Na+) pump – Na+/K+ -ATPase 2009 Cengage-Wadsworth Catalytic Proteins (Enzymes) • Functionality depends on protein & prosthetic group or coenzyme • Specificity • Maximum velocity (Vmax) - enzyme velocity at substrate saturation • Km (Michaelis constant) - concentration of substrate when reaction is at 1/2 of maximum velocity 2009 Cengage-Wadsworth Catalytic Proteins (Enzymes) • Reversibility • Regulation – Covalent modification - usually addition/removal of phosphate groups – Allosteric - enzymes with another site besides catalytic site that can bond with modulator – Induction - changes in concentrations of inducible enzymes 2009 Cengage-Wadsworth Catalytic Proteins (Enzymes) • Examples of enzyme types – Oxidoreductases - reactions in which 1 compound is oxidized, another reduced – Transferases - functional group transferred from 1 substrate to another – Hydrolases - hydrolysis of carbon-? bonds 2009 Cengage-Wadsworth Catalytic Proteins (Enzymes) – Lyases - cleavage of C-C, C-S, & C-N bonds (no hydrolysis/O-R) – Isomerases - interconversion of optical or geometric isomers – Ligases - catalyze formation of C-? Bonds (O, S, N, others) 2009 Cengage-Wadsworth Practical Clinical Application of Cellular Enzymes • Conditions for diagnostic suitability – Enzyme’s degree of organ/tissue specificity – Steep concentration gradient of enzyme activity between cell and surroundings – Enzyme must function in cytoplasm – Enzyme must be stable 2009 Cengage-Wadsworth Practical Clinical Application of Cellular Enzymes • Increased production factors – Malignant disease • Results in tumor markers 2009 Cengage-Wadsworth Apoptosis • Programmed cell death • Potential mechanisms – Intracellular stimuli • Create DNA damage • Release of cytochrome c – Extracellular stimuli • Tumor necrosis factor family of hormones or agonists – Oncosis 2009 Cengage-Wadsworth Biological Energy • ATP - major storage form in cells • Energy needed for: – Exertion – Anabolism – Active transport – Transfer of genetic information 2009 Cengage-Wadsworth Biological Energy • Energy release and consumption in chemical reactions – Energy comes from macronutrients – Transferred from one form to another • Units of energy • Free energy (G) - potential energy in bonds of nutrients that is released 2009 Cengage-Wadsworth Biological Energy • Exothermic and endothermic reactions • Activation energy - energy to raise reactants to transition state • Cellular energy • Reversibility of chemical reactions • Standard free energy change – 25°C, 1.0 atm, reactants/products at 1.0 mol/L concentrations 2009 Cengage-Wadsworth Biological Energy • Equilibrium constant (Keq) and standard free energy change • Standard pH - 7 • Nonstandard physiological conditions – In cells: ~37°C, concentrations often not 1.0 mol/L, etc. 2009 Cengage-Wadsworth Biological Energy • The role of high-energy phosphate in energy storage • Coupled reactions in the transfer of energy – Phosphorylation - adding phosphate • Reduction potentials – Standard reduction potential (E0) tendency of compound to donate & receive electrons 2009 Cengage-Wadsworth Perspective 1 Nutritional Genomics: The Foundation for Personalized Nutrition 2009 Cengage-Wadsworth Nutritional Genomics • What is nutritional genomics? • Pharmacogenomics as a model • Mechanisms underlying nutritional genomics • Nutritional genomics & lipid metabolism • Opportunities for nutrition professionals 2009 Cengage-Wadsworth