BMSC 200 Final Review PDF

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BMSC 200 Final 6: belief that living things are different from things because of some nonphysical contribute to human health Causes of Gain or loss or change of a function of an Therapeutic Target the activity of specific Indicators of Biomarkers to inform disease susceptibility, prognosis and accel...

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BMSC 200 Final Review Chapter 6: Enzymes Vitalism: belief that living things are different from non-living things because of some nonphysical element Enzymes contribute to human health as:  Causes of diseases o Gain or loss or change of a function of an enzyme  Therapeutic targets o Target the activity of specific enzymes  Indicators of Disease o Biomarkers to inform disease susceptibility, prognosis and treatments

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Enzymes accelerate the rate of reaction by a million times + Proteolysis: hydrolysis of a peptide bond  The specificity of an enzyme is due to the precise interaction of the substrate with the enzyme  Precision is from the 3D structure of the enzyme 6 Major classes of Enzymes 1) Oxidoreductases: transfer electrons between molecules (hydride ions or H atoms) 2) Transferases: transfer functional groups between molecules 3) Hydrolases: cleaves molecules by addition of water, transfer of functional groups to water 4) Lysases: adds atoms or functional groups to a double bond or removes them to form double bonds 5) Isomerases: move functional groups within a molecule to make isomeric forms 6) Ligases: join 2 molecules powered by ATP hydrolysis, makes C-C, C-S,C-O, and C-N bonds by condensation coupled to ATP cleavage Enzymes vs. Chemical Catalysts 1) Speed: good catalysts, approaching catalytic perfection, enzyme way faster 2) Conditions: function at certain physiological conditions, a lot simpler conditions 3) Specificity: high degree of specificity, including stereospecificity, more specific

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Catabolic enzymes are more specific than anabolic enzymes, they are as specific as they need to be 4) Regulation: many enzymes are responsive to the needs of the cell and organism Circe effect: some enzymes are able to catalyze reactions faster than predicated by diffusioncontrol limits, enzymes are actively drawing the substrates toward them (electrostatic reactions) Enzyme-cofactor=apoenzyme  2 group o coenzymes- complex, small, organic molecules (vitamins)-coenzymes o cofactor-metals, (helper) groups  tightly bound co-enzyme or co-factor is called a prosthetic group, permanent  free energy change provides information about spontaneity, not rate of reaction  enzymes cannot alter equilibrium of chemical reactions o only comes from free energy difference  enzymes facilitate the formation of the transition state Active Site: 3D cleft formed from groups that come from different parts of the polypeptide chain  active site is very small compared to the rest of the enzyme  active sites are unique microenvironments  substrates are bound to enzymes by multiple weak interactions  specificity of binding depends on arrangement of atoms in the binding site  induced fit or conformation selection Enzyme and substrate fit together like a glove and a hand, less like a lock and a key The relationship between the rate of reaction and activation energy is inverse and exponential Enzymes do not influence equilibrium Free Energy Changes  spontaneous, G is negative, exergonic  non-spontaneous, G is positive, endergonic  equilibrium, G is zero, no net change in [products and reactants]  G of reaction= G of products-G of reactants  G provides no information about the rate of reaction Enzymes increase rate of reaction, but do not affect the equilibrium of a reaction!

Why do enzymes lower the activation energy?  Binding effects: substrate specificity and catalytic power (basically same thing) o Substrate binding: binding & changing  Reduces entropy (decreases freedom of motion of two molecules in solution)  Removes water molecules to expose reactive groups  Aligns reactive groups of the enzyme with the substrate  Distortion of substrates  Induced fit of the enzyme in response to substrate binding o Transition state stabilization: getting it to go to the transition state  Increases interaction  Stabilizes the transition state  Enzyme distorts the substance, forcing it toward the transition state  Binds enzymes more tightly to the transition states  Transition state analogs: stable compounds whose structures resembles unstable transition states  Medicine: competitive inhibitors (looks like substrate and the enzyme will try to bind it and it won’t work) or makes catalytic antibodies (abzymes) (these will also bind the substrate, taking it away from the enzyme, looks like the transition state and the enzyme will bind with more specificity)  Chemical effects: enzyme can act upon the substrate to promote formation of the product, must have polar, ionizable side chains, also anions and cations of amino acids o Acid/base catalysis  Reaction acceleration by transfer of a proton  Often histidine o Covalent catalysis  Step 1: forms a covalent linkage to the enzyme  Step 2: regenerate the free (original) enzyme

Chapter 7: Kinetics and Regulation Rate of reaction= [P]/t (mmoles/min)  Velocity: quantity of reactant that disappears in a specific amount of time  Variables the influence rate of reaction

o pH o temperature o enzymes and substrate concentration first order reactions: reactions where velocity is directly proportional to the reactant concentrations  units of /s (s-1)  second order-two reactants o V=k[A]2 o V=k[A][B] o 1 mole/second (m-1s-1)  pseudo-first order o 2nd order look like first o [A]3 (usually 3-7)- water molecule with every unit Aldoses o Aldehyde group-C=OH at the end of the chain Ketoses o C=O in the middle of the chain When labelling start at the end closest to the double bond To decide whether it is D or L you look at the chiral carbon the farthest away from double bond

Know these sugars, he might also ask for L versions, know what the epimers are

Epimers: sugar that differ at only one chiral center  Cyclized o A hydroxyl group always must from a covalent bond to the carbon with the double bonded oxygen o 6 membered ring-pyranose  carbon 6 is outside the plane of the ring  sweeter o 5 membered ring-furanose o alpha and beta  anomers of each other (and epimers)  going form alpha to beta is a change in configuration (breaking bonds) (switches forms faster when hotter) (used to sweeten cold drinks)  mutorotation  linear intermediate  look at the hydroxyl group associated with the anomeric carbon

 above the plane- beta  below the plane- alpha o reducing agents  monosaccharides can be oxidized by iron and copper  carbonyl oxidized to a carboxyl group  allows for quantification of sugars present in blood or urine  carbonyl carbon/free anomeric carbon is the reducing end

Anomeric carbon: when carbon 1 goes from being achiral in the linear form to being chiral in the cyclical form Disaccharides: 2 monosaccharides covalently linked together through a glycosidic bond  Nomenclature  Monosaccharides involved  Ring type (pyran,furan)  Configuration (alpha or beta)  Linkages (C1-C4 etc.)  Hydroxyl group represent points of linkage  Give the configuration (alpha or beta)  Osyl for the non-reducing end  Ose for the reducing end 

Glycotransferases enzymes make higher order structures  Activated through linkage with UDP  Not as precise as proteins

Glycosidic bond: links all polymers of monosaccharides  O-glycosidic bonds occur through oxygen o All this chapter  N-glycosidic bonds occur through nitrogen Oligosaccharides: 3-20 monosaccharides Gycoconjugates: linked to proteins or lipids **Worry about glucose and galactose (pyran) what carbon is linked to what Lactose  Most mammals stop producing lactase after weaning, but some people have developed lactase persistence Sugar Derivatives

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glucosamine- lubricates joints some plants contain the sugar derivative glucosinolate as well as the enzyme myrosinase o myrosinase acts on glucosinolate and makes isothiocynate- tastes like shit so herbivores don’t eat the plant, horseradish and wasabi o myrosinase and glucosinolate are stored separately but they come together upon tissue damage glycolipids o blood group antigens o different patterns of sugars glycoproteins o covalently attached protein o mostly protein a little sugar o N linked  Aspargine o O linked  Serine or threonine o Erythropoietin EPO  Treatment for anemia  You can tell if you have received artificial kind  So people aren’t doping proteoglycans o mostly sugar, little protein o gel-like material, extracellular matrix (ground substance)  holds cells together  lubes and cushions o glycosaminoglycan o heavily hydrated and all these charges are repelling each other

Polysaccharides: 20+ monomers  energy storage, structural roles, cushioning and lubrication  homopolysaccharides: polymers made of one kind on monosaccharides  heteropolysaccharides: more than one kind of monosaccharides o both can be branched or unbranched  energy storage o D-glucose o Both are heavily hydrated structures o Starch  2 molecules  amylose o linear polymer of glucose residues through alpha (1-4) bonds  amylopectin

o alpha(1-4) linked glucose residues with an alpha(1-6) branch point every 24-30 residues o alpha(1-4) cut by amylase (in spit) o alpha(1-6) cut by debranching enzyme o feather-like o lots of non-reducing ends  remove glucose from the non-reducing ends  found In plants and fungi  plants o glycogen  stored in liver and skeletal muscles, in all cells  same as amylopectin but branching points every 10 residues  more branches means faster mobilization  more non-reducing end (break down from this end) o Cellulose  Plant cell walls (fiber)  Over half of the carbon in the biosphere  Linear, homopolysaccharide of glucose  B(1-4) glycosidic residues  Cannot be cut by amylase (only alpha) o Chitin  Hard component of exoskeletons  Homopolysaccharide of N-acetylglucosamine residues  Difference between cellulose and chitin is the replacement of hydroxyl group at C2 with acetylated amino group

Lipids Structure and Function  Hydrophobic o Insoluble in water  Can be extracted from cells with organic solvents of lower polarity o Diethyl ether, chloroform, methanol etc.  Low molecular weight compared to protein and DNA  Small molecules, usually not polymers Reductionist: reduce the complexity of a living cell to study biochemistry  Functions o Energy storage (fat in animals, oil in plants)

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Fat (solid at room temp) occupies most of the intracellular space in adipocytes in animal tissues  Storage of fat lasts a few weeks  Glycogen only lasts a day  Oil (liquid at room temp) droplets in plant storage cells Structural roles  Building blocks of cell membranes  Polar head groups-hydrophobic tails-polar head groups Biochemical signals  Messengers within the cells, hormones Enzyme cofactors Pigments

Triacylglycerol are fatty acid esters of glycerol  Nature wants to build complex structures from simple building blocks  Triacylglycerol are storage lipids in animals and plants  Fatty acid tails have an even number of atoms between 12 and 24 o Fatty acids at position 1-3 of glycerol moiety are usually different  Ester bonds  Saturated have no double bonds  Unsaturated have 1-3 double bonds between C9-C10, C12-C13, C15-C16 Nomenclature  first number is the number of the carbons  know how to name  count carbons from carboxyl end

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the longer the chain the higher the melting point more double bonds make the melting point lower

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double bonds introduce kinks in the hydrocarbon tails resulting in less packing and higher extent of thermal motion double bonds are usually in the cis-configuration o trans configuration- man-made, makes bad cholesterol van der Waals interactions packs saturated fatty acids

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Fat is a more efficient fuel, but carbs burn faster  less oxygenated fuels burn more efficiently  triacylglycerols have lower oxidation states than carbs  fat doesn’t need hydration with water  fat stores more energy/gram than carbs  glycogen is hydrated, dead weight  glycogen has a polymer glucose Membrane Lipids  every case you have a backbone, 2 chains, and at position 3 you have a polar functional group (phos, sulphur, monosaccharide)  storage lipids are highly hydrophobic

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Glycerophospholipids are derivatives of phosphatidic acid o Usually the fatty acid at C1 is saturated and has 16-18 carbons o The fatty acid at C2 is unsaturated and has 18-20 carbon atoms o This allows the lipid to adjust phase when the temperature changes so it can maintain proper fluidity o Know the names of the head groups and recognize the structures o common in animal and bacteria cells plants contain galactolipids and sulfolipids o Instead of phosphate for polar head o Because phos is usually the limiting nutrient needed for critical functions Some lipids contain ester bonds instead of ester bonds o Ether bond are more stable and resistant to enzyme digestion by lipases o Archaea glycerol diacylglycerol tetra ether lipids are very stable and maintain membrane integrity in extreme environments The backbone of sphingolipids if make of sphingosine instead of glycerol o Neural cells o Sphingomyelin o Head group can contain phosphothanlamine or phosocholine o Cerebrosides re found in the plasma membrane

 Contain galactose in neural cells and glucose in others Gangliosides contain sialic acid  Negatively charged at pH 7 o Glycosphingolipids on the surface of red blood cells to determine blood type  Oligosaccharides that form head groups of the sphingolipids on the blood cells, also attached to some blood proteins Phospholipids and sphingolipids are degraded by enzymes and lysosomes o Constantly recycled o Lipases cleave the bonds between the head groups and the fatty acid chains from the backbone o Sugar units of gangliosides by gangliosidases o

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Sterols  Have four fused carbon rings  Cholesterol o Only bad when it ends up in the blood vessels and other bad places  Hormones  bile acids o taurocholic o natural detergents made in the liver that help to emulsify oils in the digestive tract  amphipathic molecules that have a charged or polar head group that interact with water and a bulky nonpolar tail that binds to lipids o came from cholesterol  steroid hormones: have steroid nucleus, 4 fused rings, no charged head group making it a detergent, hydroxyl group have a OH group on carbon 17 making it more soluble to get into the blood stream o testosterone o estradiol  ovaries and the placenta o cortisol  produced in the adrenal cortex  regulates glucose metabolism o cant be as hydrophobic because hormones have to travel in the blood  Vitamin D is a precursor of a hormone that regulates Ca uptake in the intestine o Critical step in the synthesis of vitamin D3 is the cleavage of a bond in the skin cells caused by the UV component of sunlight o Vitamin D deficiency causes abnormal bone development  Rickets- insufficient Ca uptake in the body  Weird bone development- mostly effects kids  Lack of skin exposure to sunlight  Poor people who worked a lot and having a bad diet and wearing heavy clothes  Our food is supplemented- milk o Vitamin A1 is a precursor of a visual pigment retinal and of hormone retinoic acid  Beta carotene is cleaved to produce vitamin A-retinol  Photoreceptor in the human eye- visual rhodopsin  Retinol absorbs light in the human retina

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Retinal is a cofactor of rhodopsin (light receptor protein in the human eye  Red eyes in pictures comes from retinal  Isoprene is a common building block of many lipid cofactors  Hydrocarbon tail and beta carotene and vitamin A are built from isoprene units Vitamins E and K and the lipid quinones are redox cofactors o Vitamin E is an antioxidant that prevents oxidative damage to lipids, particularly to the unsaturated hydrocarbon tail  Called tocopherols  Hydrophobic isoprenoid tail makes tocopherols highly soluble in lipids  Aromatic ring prevents damage

Vitamin A and E have a Quinone ring and an isoprene chain  Oxidized (quinone)  Reduced (quinol)  Ubiquinone can carry a proton donor to a protein acceptor inside the membrane and protons form one side of the membrane to the other  Vitamin K- isoprene units (5 carbon units), 2 rings  Vitamin A has just one ring

Chapter 12: Biological Membranes Functions  Physically separate cells from the external medium and the intracellular compartments (organelles) from cytosol. This is necessary for segregation of proteins involved in different biological processes and to maintain required concentrations of small biomolecules  Facilitate transport of substrates and ion in the cell  Membranes of mitochondria, chloroplasts and plasma membrane of bacteria are the sites of energy conversion in living cells  Transient changes of electric potential on the plasma membrane of neuron cells are the basis of nervous system activity  Membrane proteins and lipids are involved in cell-cell interactions  Membranes contain receptors for hormones and other biochemical signals Lipid bilayer  Micelle o Individual units are wedge shaped o Fatty acids and detergents favor this o Liposomes-look like a micelle but with an aqueous cavity, produced artificially from pure lipids  Bilayers o Individual units are cylindrical

o Glycerophospholipids and sphingolipids o Unstable and close to form membrane vesicles Fluid Mosaic Model  Lipids and proteins can freely diffuse in the plane of the membrane  Bimolecular reaction in the membrane can be more efficient than in solution because the probability of molecular collisions in a 2D plane is higher than in a 3D plane Sphingolipids and cholesterol cluster together in membrane rafts  Membranes have a mixture of different lipids that do not have well-defined phase transitions  Sphingolipids associate with cholesterol (planar structure) to form lipid rafts o Domains of liquid-ordered lipid surrounded largely by disordered fluid phospholipid o Stabilized by interaction between the cholesterol ring and long saturated hydrocarbon tails of sphingolipids o Have attachment points for peripheral membrane proteins that are anchored in the membrane by 2 covalently attached saturated acyl chains or GPI o Protein molecules get on these rafts Membrane Proteins  Peripheral o Attached to the membrane either through non-covalent membrane interactions with other proteins or by covalently linked lipid anchors o Either mostly in the cell or mostly out c o Can be removed by enzymes o Attachment  Proteins anchored to the membrane by GPI are always outside the cell  Attached by ester bonds  Proteins anchored by fatty acyl chains or poly isoprene tail are always inside the cell  Integral o Immersed in the membrane and usually span the lipid bilayer with parts of the protein exposed on both sides o Can be extracted from the membrane with detergents  Distribution of amino acids o Charged residues (asp, glu, arg, lys,) mostly located outside the membrane  Except for a few involved in interaction with ions or polar substrates in the active sites of the protein o Residues with a polar side (valine, leu, ala) chains are usually inside the hydrophobic slab of the of the membrane o Try and Tyr (aromatic) are clustered along the edges of the membrane  2 main secondary structures

o B-barrel (everything is hydrogen bonded, sheet closed on itself so that there aren’t exposed dipoles) and a-helical bundle (most common integral) o Peptide groups in the bilayer core are H-bonded in regular secondary structure  Transfer of dipoles on the protein backbone to the apolar core of the bilayer would be associated with high energy penalty  Carbonyl and amide groups of the protein must be hydrogen bonded  The apolar environment in the middle of the bilayer stabilizes regular secondary structures Membrane fusion

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Leaving cellexocytosis Reverse is exocytosis Viruses trick the cell into taking it in Neural transmission o Send signals down axons o Impulse reaches another cell o Re...