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13 - Enzymes, Vitamins and Hormones
CHM1033
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Enzymes are Biological Catalysts
Enzymes are proteins that catalyze nearly all the chemical reactions taking place in the cells of the body Rate = k[A]x[B]y increase the rate of reaction by lowering the energy of activation (increasing rate constant, k = Ae-Ea/RT) General, Organic, and Biological Chemistry
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General, Organic, and Biological Chemistry
Active Site The active site is a region within an enzyme that fits the shape of the reacting molecule, called a substrate contains amino acid R groups that bind the substrate releases products when the reaction is complete General, Organic, and Biological Chemistry
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General, Organic, and Biological Chemistry
Enzyme Specificity Enzymes may recognize and catalyze a single substrate a group of similar substrates a particular type of bond General, Organic, and Biological Chemistry
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Isoenzymes Isoenzymes
catalyze the same reaction in different tissues in the body such as lactate dehydrogenase (LDH), which converts lactate to pyruvate, consist of five isoenzymes can be used to identify the organ or tissue involved in damage or disease such as LDH have one form more prevalent in heart muscle and another form in skeletal muscle and liver tissue General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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Isoenzymes (continued)
General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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General, Organic, and Biological Chemistry
Diagnostic Enzymes Diagnostic enzymes determine the amount of damage in tissues that are elevated may indicate damage or disease in a particular organ General, Organic, and Biological Chemistry
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Competitive Inhibitor
A competitive inhibitor has a structure that is similar to that of the substrate competes with the substrate for the active site has its effect reversed by increasing substrate concentration Noncompetitive inhibitors do NOT bind to active site like the substrate General, Organic, and Biological Chemistry
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Learning Check 1. Enzymes are biological_________.
2. T/F – Enzymes slow down chemical reactions 3. T/F – Enzymes shift equilibrium to the right. 4. What is an active site? 5. T/F Diagnostic enzymes are a type of isoenzyme. 6. You want to test the reaction rate of sucrase and enzyme that hydrolyzes sucrose. When your friend adds a chemical, you need to add more sucrose to get the rate back to normal. What is the chemical? What would the chemical look like?
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Enzyme Cofactors simple enzyme - an active enzyme that consists only of protein. cofactors make enzymes active such as metal ions or small molecules. Prepares the active site for catalytic activity coenzyme a type of cofactor that is a small organic molecule such as a vitamin. General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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Metal Ions as Cofactors
Many active enzymes require a metal ion. For example, Zn2+, a cofactor for carboxypeptidase, stabilizes the carbonyl oxygen during the hydrolysis of a peptide bond. General, Organic, and Biological Chemistry
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Some Enzymes and Their Cofactors
General, Organic, and Biological Chemistry
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Learning Check Identify each enzyme as 1) a simple enzyme
2) an enzyme that required a cofactor A. requires Mg2+ for hydrolysis of phosphate esters B. requires vitamin B3 to transfer an acetyl group C. is active with four polypeptide subunits General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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Water-soluble vitamins are soluble in aqueous solutions
cofactors for many enzymes not stored in the body General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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is part of coenzyme A needed for energy production
part of the coenzyme thiamin pyrophosphate (TPP), used to decarboxylate -keto carboxylic acids is part of coenzyme A needed for energy production is involved in glucose and cholesterol synthesis has an RDA of 5 mg found in the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) two forms of vitamin B6, which are converted to the coenzyme pyridoxal phosphate (PLP) required in the transamination of amino acids and decarboxylation of carboxylic acids
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is required in collagen synthesis and healing of wounds
is a coenzyme for enzymes that transfer methyl groups and produce red blood cells is part of the coenzyme nicotinamide adenine dinucleotide (NAD+) involved in oxidation–reduction reactions
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General, Organic, and Biological Chemistry
Biotin Biotin is a coenzyme for enzymes that transfer carboxyl groups has an RDA of 30 g deficiencies include dermatitis, loss of hair, fatigue, and anemia Binds with a protein from Streptomyces avidii with the strongest non-covalent binding affinity known thus far. Biotin-streptavidin technology is wide-spread in many biological/chemical applications General, Organic, and Biological Chemistry
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Folic Acid (Folate) consists of pyrimidine, p-aminobenzoic acid, and glutamate forms the coenzyme THF used in the transfer of methyl groups and is involved in the synthesis of nucleic acids General, Organic, and Biological Chemistry Copyright © 2010 Pearson Education, Inc.
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General, Organic, and Biological Chemistry
Fat-Soluble Vitamins Fat-soluble vitamins are vitamins A, D, E, and K soluble in lipids but not in aqueous solutions stored in the body important in vision, bone formation, antioxidants, and blood clotting General, Organic, and Biological Chemistry
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Cellular Communication
Both single- and multicellular organisms must respond to physical and chemical changes in their environment. Single-celled organisms can communicate to each other for sexual reproduction, resource-sharing/competition and colony formation. Cell-cell communication even more important for multicellular organisms. Three types of molecules involved in communication: Chemical Messengers (ligands) - small or macromolecules that interact with cellular receptors by binding to their ligand-binding sites. Receptors – proteins that bind to ligands and effect change in the cell. Located on cell surface, in the membrane or the cell or subcellular organelles or free within the cytoplasm or organelles. Secondary messengers – usually carry the message from the receptor to the inside of the cell and amplify the message.
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4 Forms of Intercellular Signaling
NOTE: Many of the same signaling molecules are used in paracrine, synaptic and endocrine signaling; the differences lie in the speed and selectivity with which the signals are delivered to their targets. Contact-dependent – Signal molecules remain on the signaling cell surface and another cell must interact directly with that cell to receive the signal. Or molecules exchanged between cells through gap junctions. Seen during development and immune responses. Paracrine – Signals are released into the extracellular space and act locally on the neighboring cells Synaptic – performed by neurons that transmit their signals electrically along their axons and release neurotransmitters at synapses. Axons- long fiber-like projection of neuron to create presynaptic nerve ending sometimes far away from neuron cell body Synapses – fluid-filled spaces between axons and the receiving cell body or dendrite (postsynaptic) . Neurotransmitters – A chemical messenger between a neuron and another target cell: another neuron, muscle cell or cell of a gland. Stored at the presynaptic site in vesicles. Endocrine – Endocrine cells secrete hormones into the bloodstream for distribution throughout the body. Hormone – a chemical messenger released by an endocrine gland into the bloodstream and transported there to reach its target cell. Some chemicals that act as neurotransmitters at synapses can also be hormones (see table 16.2)
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Figure 15-4 Molecular Biology of the Cell (© Garland Science 2008)
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Communication by the Nervous and Endocrine Systems
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurotransmitter Nerve impulse Neuron Target cells (a) Nervous system Endocrine cells Target cells Hormone in bloodstream (b) Endocrine system
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Chemistry of Ligands (Hormones and Neurotransmitters)
1. Acetylcholine Derived from choline (alcohol amine) from the diet 2. Monoamines (biogenic amines) Derived from amino acids Secreted by adrenal, pineal, and thyroid glands Epinephrine, norepinephrine, melatonin, and thyroid hormone All hormones are made from either lipids or amino acids with carbohydrate added to make glycoproteins epinephrine
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Chemistry of the Ligands (Hormones, Neurotransmitters, etc.)
3. Peptides and glycoproteins Created from chains of amino acids Secreted by pituitary and hypothalamus Oxytocin, endorphins, vassopressin antidiuretic hormone, insulin, releasing and inhibiting hormones, and anterior pituitary hormones. 4. Lipids and phospholipids Eicosanoids – from the fatty acid arachodonic acid etc. Prostaglandins, thromboxanes, leukotrienes Steroids Derived from cholesterol Secreted by gonads and adrenal glands Estrogens, progesterone, testosterone, cortisol, corticosterone, aldosterone, DHEA, and calcitriol O I C H OH CH3 Testosterone HO Estradiol (a) Steroids COOH H2N CH2 Thyroxine (b) Monoamines Epinephrine CH NH S Angiotensin II Oxytocin Antidiuretic hormone (c) Peptides Tyr Arg Asp lle His Pro Phe Cys GIn Asn Gly Leu Val Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Chemistry of Receptors
Ligands stimulate only those cells that have receptors for them Receptors are protein or glycoprotein molecules On plasma membrane, in the cytoplasm, or in the nucleus Receptors act like switches turning on metabolic pathways when ligands binds to them Usually each target cell has a few thousand receptors for a given ligand Receptor–ligand interactions exhibit specificity and saturation Specific receptor for each hormone Saturated when all receptor molecules are occupied by hormone molecules
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What Happens When Ligand Binds to Receptor?
Signal Transduction A cascade of events signal of a messenger delivered to its receptor is carried inside the target cell signal amplified into many signals result in protein modifications, enzyme activation, opening of membrane channels, gene activation, etc.
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Ligand Type 4: Lipid Hormones
Steroids and thyroid hormone are hydrophobic Bind to transport proteins (albumins and globulins synthesized by the liver) Bound hormones have longer half-life Protected from liver enzymes and kidney filtration Only unbound hormone leaves capillaries to reach target cell Transport proteins protect circulating hormones from being broken down by enzymes in the plasma and liver, and from being filtered out of the blood by the kidneys
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receptors do not have to shuttle them across the cell membrane.
Nuclear hormones interact with receptors in the Nuclear hormone receptor superfamily Nuclear hormones are hydrophobic or lipid. Diffuse. through cell membranes receptors do not have to shuttle them across the cell membrane. Note the chemical connections 16G on estrogen receptor and pollutants p390 Figure Molecular Biology of the Cell (© Garland Science 2008)
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Hormone Receptors and Mode of Action
Hydrophobic hormones Penetrate plasma membrane and enter nucleus Act directly on the genes changing target cell physiology Estrogen, progesterone, thyroid hormone act on nuclear receptors Take several hours to days to show effect due to lag for protein synthesis Hydrophilic hormones Cannot penetrate into target cell Must stimulate physiology indirectly Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hydrophilic hormone Receptor in plasma membrane Target cell Transport protein Second- messenger activation Free hormones Bound hormone Hydrophobic hormone Receptor in nucleus Tissue fluid Blood
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Steroids and Thyroid Hormone
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid hormone enters target cell by diffusion, mostly as T4 with little metabolic effect Within target cell, T4 is converted to more potent T3 TBG T3 T4 Various metabolic effects Protein synthesis mRNA DNA T4 I T3 Blood Tissue fluid Target cell
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Steroids bind to steroid receptors activate transcription
Figure 15-15a Molecular Biology of the Cell (© Garland Science 2008) Nucleus by binding to response elements and recruiting proteins to form a preinitiation complex Estrogen receptor
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Learning Check 1. Is estrogen a hormone, local mediator, or neurotransmitter? Why? 2. What type of biomolecule is estrogen? 3. When estrogen binds to its receptor, the receptor turns on the expression of certain genes that promote cell growth and division. What type of biomolecule did it bind? 4. Tamoxifen is an anti-cancer drug that binds to the estrogen receptor. Is it an agonist or antagonist?
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Most pharmaceuticals target these communication pathways
Antagonist – a drug that blocks receptor response or activity Agonist - a drug that stimulates receptor activity Drugs that influence ligand concentration – Drugs that decrease ligand concentration by control of their release from storage Drugs that increase the ligand concentration by inhibiting its removal from the receptors Drugs inhibit or activate specific enzymes inside the cell
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Anti-Inflammatory Drugs -blocks prostaglandin synthesis from fatty acids
Cortisol and corticosterone Steroidal anti-inflammatory drugs (SAIDs) Block release of arachidonic acid (a fatty acid) from plasma membrane and inhibit synthesis of eicosanoids Disadvantage—produce symptoms of Cushing syndrome Aspirin, ibuprofen, and celecoxib (Celebrex) Nonsteroidal anti-inflammatory drugs (NSAIDs) COX inhibitors since block cyclooxygenase (COX) COX – key enzyme in prostaglandin pathway Do not affect lipoxygenase function or leukotriene production Useful in treatment of fever and thrombosis Inhibit prostaglandin and thromboxane synthesis
