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An Introduction to Metabolism
Chapter 8 An Introduction to Metabolism
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What You Need To Know: Examples of endergonic and exergonic reactions.
The key role of ATP in energy coupling. That enzymes work by lowering the energy of activation. The catalytic cycle of an enzyme that results in the production of a final product. The factors that influence enzyme activity.
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__________________________ is the totality of an organism’s chemical reactions
How cells manage the materials and energy resources of a cell
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dehydration synthesis synthesis ____________________ reactions
Metabolism __________________________________________________ _________________ bonds between molecules dehydration synthesis synthesis ____________________ reactions hydrolysis digestion _____________________reactions
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What are 2 metabolic pathways?
_______________ energy by _____________________ complex molecules into simpler compounds Eg. digestive _______________ break down food release energy __________________ pathways ___________________ energy to ____________ complex molecules from simpler ones Eg. amino acids link to form muscle _________
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dehydration synthesis (synthesis)
Examples dehydration synthesis (synthesis) Catabolic or Anabolic? enzyme + H2O Catabolic or Anabolic? hydrolysis (digestion) enzyme + H2O
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Energy = capacity to do work
_____________ energy (KE): energy associated with _________________ _________ (thermal energy) is KE associated with random movement of atoms or molecules _____________ energy (PE): ____________ energy as a result of its position or structure __________________ energy is PE available for release in a chemical reaction Energy can be __________________ from one form to another Eg. chemical mechanical electrical
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Thermodynamics is the study of energy transformations that occur in nature
A __________ system, such as liquid in a thermos, is isolated from its surroundings In an __________ system, energy and matter can be transferred between the system and its surroundings Organisms are _____________ systems.
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The First Law of Thermodynamics
The ___________ of the universe is ___________ Energy can be _________________ and ________________ Energy cannot be ______________ or ______________ Also called the principle of Conservation of Energy
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The Second Law of Thermodynamics
Every energy transfer or transformation ______________________________(disorder) of the universe During every energy transfer or transformation, some energy is __________, often lost as ________
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Chemical Reactions & Energy
__________________: part of a system’s energy available to perform ________ ______ = change in free energy _____________ reaction: energy is __________ _________________________ reaction G < 0 _________________reaction: energy is _________ Absorb free energy G > 0
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Chemical reactions & energy
Some chemical reactions _____________________ ________________________ digesting polymers hydrolysis = ________________ Some chemical reactions require ______________________________ building polymers dehydration synthesis = ________________ digesting molecules= LESS organization= lower energy state building molecules= MORE organization= higher energy state
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Endergonic vs. exergonic reactions
- energy released - digestion energy invested synthesis +G -G G = change in free energy = ________________________________
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TURN AND TALK!
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TURN AND TALK Questions!
What type of reaction is this? (exergonic or endergonic) Is energy being released or required/absorbed? Is this a synthesis or a digestion reaction? Is this reaction spontaneous or not?
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TURN AND TALK!
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TURN AND TALK Questions!
What type of reaction is this? (exergonic or endergonic) Is energy being released or required/absorbed? Is this a hydrolysis or synthesis reaction? Is this reaction anabolic or catabolic?
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Energy & life energy energy Organisms require energy to live
where does that energy come from? ______________________ exergonic reactions (releasing energy) with endergonic reactions (needing energy) energy + + digestion synthesis energy + +
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Let’s Dig Deeper Watch Dr. Anderson explain “Free Energy”
Complete the Video Review Sheet Optional: Watch Bozeman’s video on “Gibbs Free Energy”
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A cell does three main kinds of work:
Mechanical Transport Chemical Cells manage energy resources to do work by energy coupling: using an ____________________ process to drive an ___________________________ one
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What molecule is this?
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________ (adenosine triphosphate) is the cell’s main energy source in energy coupling
ATP = adenine + ribose + 3 phosphates
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How does it compare to ATP?
What molecule is this? How does it compare to ATP?
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When the bonds between the phosphate groups are broken by __________ ___________________
This release of energy comes from the chemical change to a state of ___________ free energy, not in the phosphate bonds themselves
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DISCUSS: Is this reaction endothermic or exothermic?
DISCUSS: Is this reaction exergonic or endergonic?
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How ATP Performs Work Exergonic release of Pi is used to do the endergonic work of cell When ATP is hydrolyzed, it becomes ________ (adenosine diphosphate)
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b. Why would taking DNP be dangerous?
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Mechanical work: ATP phosphorylates motor proteins
Protein moved Mechanical work: ATP phosphorylates motor proteins Membrane protein ADP ATP + P i P P i Solute Solute transported Transport work: ATP phosphorylates transport proteins P NH2 + NH3 Glu + P i Glu Reactants: Glutamic acid and ammonia Product (glutamine) made Chemical work: ATP phosphorylates key reactants
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What drives reactions? If reactions are “downhill”, why don’t they just happen spontaneously? because _______________________ bonds are ________________ bonds starch
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What is Activation Energy?
Breaking down large molecules requires an initial input of energy This is called _______________________ large biomolecules are stable must _________ energy to break bonds Need a spark to start a fire energy cellulose CO2 + H2O + heat
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Too much activation energy for life
amount of energy needed to destabilize the bonds of a molecule moves the reaction over an “energy hill” Not a match! That’s too much energy to expose living cells to! glucose 2nd Law of thermodynamics Universe tends to disorder so why don’t proteins, carbohydrates & other biomolecules breakdown? at temperatures typical of the cell, molecules don’t make it over the hump of activation energy but, a cell must be metabolically active heat would speed reactions, but… would denature proteins & kill cells
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Reducing Activation energy
_______________________ reduce the amount of energy to start a reaction Pheeew… that takes a lot less energy! uncatalyzed reaction catalyzed reaction NEW activation energy reactant product
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So what’s a cell got to do to reduce activation energy?
Catalysts So what’s a cell got to do to reduce activation energy? get help! … chemical help… G
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What are Enzymes? ______________________________________
Biological catalysts ______________________________________ _____________________chemical reactions increase _____________ of reaction without being ______________________ ______________________ activation energy don’t change free energy (G) released or required required for most biological reactions highly ___________________ thousands of different enzymes in cells control reactions of life
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Enzymes vocabulary substrate product active site active site products
____________________ which binds to enzyme enzyme-substrate complex: temporary association product end ___________ of reaction active site enzyme’s catalytic site; substrate fits into active site active site products substrate enzyme
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Properties of enzymes Reaction _________________________
each enzyme works with a specific _____________ chemical fit between active site & substrate H bonds & ionic bonds Not consumed in reaction (___________________) single enzyme molecule can catalyze thousands or more reactions per second enzymes ________________________ by the reaction Affected by cellular conditions any condition that affects protein ______________ temperature, pH, salinity
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Enzymes named for reaction they catalyze
Naming conventions Enzymes named for reaction they catalyze sucrase breaks down ________________ proteases break down ________________ ____________________ break down lipids DNA polymerase builds _______ adds nucleotides to DNA strand pepsin breaks down proteins (__________________)
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Lock and Key model ____________________ model of enzyme action
substrate fits into 3-D structure of enzyme’ active site H bonds between substrate & enzyme like “key fits into lock”
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_______________________________model
More accurate model of enzyme action 3-D structure of enzyme fits substrate substrate binding cause enzyme to __________ _______________ leading to a tighter fit “___________________________________” bring chemical groups in position to catalyze reaction
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INDUCED FIT: ENZYME FITS SNUGLY AROUND SUBSTRATE -- “CLASPING HANDSHAKE”
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How does it work? Variety of mechanisms to lower activation energy & speed up reaction synthesis active site ______________ substrates in correct position for reaction enzyme brings substrate closer together digestion active site binds substrate & puts stress on ________ that must be broken, making it easier to separate molecules
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___________________________: ENZYME FITS SNUGLY AROUND SUBSTRATE -- “CLASPING HANDSHAKE”
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What Factors Affect Enzyme Function?
____________________ concentration ____________________ pH Living with oxygen is dangerous. We rely on oxygen to power our cells, but oxygen is a reactive molecule that can cause serious problems if not carefully controlled. One of the dangers of oxygen is that it is easily converted into other reactive compounds. Inside our cells, electrons are continually shuttled from site to site by carrier molecules, such as carriers derived from riboflavin and niacin. If oxygen runs into one of these carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulfur atoms and metal ions in proteins. To make things even worse, free iron ions in the cell occasionally convert hydrogen peroxide into hydroxyl radicals. These deadly molecules attack and mutate DNA. Fortunately, cells make a variety of antioxidant enzymes to fight the dangerous side-effects of life with oxygen. Two important players are superoxide dismutase, which converts superoxide radicals into hydrogen peroxide, and catalase, which converts hydrogen peroxide into water and oxygen gas. The importance of these enzymes is demonstrated by their prevalence, ranging from about 0.1% of the protein in an E. coli cell to upwards of a quarter of the protein in susceptible cell types. These many catalase molecules patrol the cell, counteracting the steady production of hydrogen peroxide and keeping it at a safe level. Catalases are some of the most efficient enzymes found in cells. Each catalase molecule can decompose millions of hydrogen peroxide molecules every second. The cow catalase shown here and our own catalases use an iron ion to assist in this speedy reaction. The enzyme is composed of four identical subunits, each with its own active site buried deep inside. The iron ion, shown in green, is gripped at the center of a disk-shaped heme group. Catalases, since they must fight against reactive molecules, are also unusually stable enzymes. Notice how the four chains interweave, locking the entire complex into the proper shape. catalase
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1) Enzyme concentration
What’s happening here?! reaction rate enzyme concentration
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Enzyme concentration as ____ enzyme = ____ reaction rate more enzymes = more frequently collide with substrate reaction rate _____________________ substrate becomes ________________ factor not all enzyme molecules can find substrate Why is it a good adaptation to organize the cell in organelles? Sequester enzymes with their substrates! enzyme concentration reaction rate
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2) Substrate concentration
What’s happening here?! reaction rate substrate concentration
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Substrate concentration
as ___ substrate = ___ reaction rate more substrate = more frequently collide with enzyme reaction rate levels off all enzymes have active site engaged enzyme is ______________________ maximum rate of reaction Why is it a good adaptation to organize the cell in organelles? Sequester enzymes with their substrates! substrate concentration reaction rate
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3) Temperature What’s happening here?! 37° reaction rate temperature
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Temperature Optimum T° Heat: increase beyond optimum T°
greatest number of molecular collisions human enzymes = 35°- 40°C body temp = 37°C Heat: increase beyond optimum T° increased energy level of molecules ________________________ in enzyme & between enzyme & substrate H, ionic = weak bonds denaturation = _________________________(3o structure) and __________________________________________ Cold: decrease T° molecules move ________________ decrease collisions between enzyme & substrate
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Enzymes and temperature
Different enzymes function in different organisms in different environments hot spring bacteria enzyme human enzyme 37°C 70°C reaction rate temperature (158°F)
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How do ectotherms do it? Enzymes work within narrow temperature ranges. Ectotherms, like snakes, do not use their metabolism extensively to regulate body temperature. Their body temperature is significantly influenced by environmental temperature. Desert reptiles can experience body temperature fluctuations of ~40°C (that’s a ~100°F span!). What mechanism has evolved to allow their metabolic pathways to continue to function across that wide temperature span?
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4) pH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 What’s happening here?! pepsin
trypsin pepsin reaction rate trypsin 1 2 3 4 5 6 7 8 9 10 11 12 13 14 pH
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pH changes in pH adds or remove _________
disrupts ____________, disrupts ______ shape disrupts attractions between charged amino acids affect ______& ______ structure ______________________ protein optimal pH? most human enzymes = pH ________ depends on localized conditions pepsin (stomach) = pH 2-3 trypsin (small intestines) = pH 8 7 2 1 3 4 5 6 8 9 10 11
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5) Salinity What’s happening here?! reaction rate salt concentration
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_____________ concentration
changes in salinity adds or removes cations (+) & anions (–) disrupts ________, disrupts ______ shape disrupts attractions between charged amino acids affect 2°& 3° structure denatures protein enzymes intolerant of extreme salinity Dead Sea is called dead for a reason!
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Compounds which __________ enzymes
6) Activators Compounds which __________ enzymes Fe in hemoglobin cofactors non-protein, small _______________ compounds & ions Mg, K, Ca, Zn, Fe, Cu bound within enzyme molecule coenzymes non-protein, ____________________ molecules bind temporarily or permanently to enzyme near active site many _______________________ NAD (niacin; B3) FAD (riboflavin; B2) Coenzyme A Hemoglobin is aided by Fe Chlorophyll is aided by Mg Mg in chlorophyll
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Compounds which ________________ enzymes
7) Inhibitors Compounds which ________________ enzymes molecules that _________________ enzyme activity competitive inhibition noncompetitive inhibition (allosteric) irreversible inhibition feedback inhibition
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A) Competitive Inhibitor
Inhibitor & substrate “__________________” for ___________________________ penicillin blocks enzyme bacteria use to build cell walls disulfiram (Antabuse) treats chronic alcoholism blocks enzyme that breaks down alcohol severe hangover & vomiting 5-10 minutes after drinking Overcome by _________________ substrate concentration saturate solution with substrate so it out-competes inhibitor for active site on enzyme Ethanol is metabolized in the body by oxidation to acetaldehyde, which is in turn further oxidized to acetic acid by aldehyde oxidase enzymes. Normally, the second reaction is rapid so that acetaldehyde does not accumulate in the body. A drug, disulfiram (Antabuse) inhibits the aldehyde oxidase which causes the accumulation of acetaldehyde with subsequent unpleasant side-effects of nausea and vomiting. This drug is sometimes used to help people overcome the drinking habit. Methanol (wood alcohol) poisoning occurs because methanol is oxidized to formaldehyde and formic acid which attack the optic nerve causing blindness. Ethanol is given as an antidote for methanol poisoning because ethanol competitively inhibits the oxidation of methanol. Ethanol is oxidized in preference to methanol and consequently, the oxidation of methanol is slowed down so that the toxic by-products do not have a chance to accumulate.
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B) Non-Competitive Inhibitor
Inhibitor binds to site ____________________active site _______________________________binds to allosteric site causes enzyme to change _____________ _________________________________________ change active site is no longer functional binding site keeps enzyme ______________________ Examples: some anti-cancer drugs inhibit enzymes involved in DNA synthesis stop DNA production stop division of more cancer cells cyanide poisoning irreversible inhibitor of Cytochrome C, an enzyme in cellular respiration stops production of ATP Basis of most chemotherapytreatments is enzyme inhibition. Many health disorders can be controlled, in principle, by inhibiting selected enzymes. Two examples include methotrexate and FdUMP, common anticancer drugs which inhibit enzymes involved in the synthesis of thymidine and hence DNA. Since many enzymes contain sulfhydral (-SH), alcohol, or acid groups as part of their active sites, any chemical which can react with them acts as a noncompetitive inhibitor. Heavy metals such as silver (Ag+), mercury (Hg2+), lead ( Pb2+) have strong affinities for -SH groups. Cyanide combines with the copper prosthetic groups of the enzyme cytochrome C oxidase, thus inhibiting respiration which causes an organism to run out of ATP (energy) Oxalic and citric acid inhibit blood clotting by forming complexes with calcium ions necessary for the enzyme metal ion activator.
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C) Irreversible inhibition
Inhibitor ______________________ binds to enzyme ______________________________ permanently binds to _________________ site permanently binds to __________________ site permanently changes shape of enzyme nerve gas, sarin, many insecticides (malathion, parathion…) cholinesterase inhibitors doesn’t breakdown the neurotransmitter, acetylcholine Another example of irreversible inhibition is provided by the nerve gas diisopropylfluorophosphate (DFP) designed for use in warfare. It combines with the amino acid serine (contains the –SH group) at the active site of the enzyme acetylcholinesterase. The enzyme deactivates the neurotransmitter acetylcholine. Neurotransmitters are needed to continue the passage of nerve impulses from one neurone to another across the synapse. Once the impulse has been transmitted, acetylcholinesterase functions to deactivate the acetycholine almost immediately by breaking it down. If the enzyme is inhibited, acetylcholine accumulates and nerve impulses cannot be stopped, causing prolonged muscle contration. Paralysis occurs and death may result since the respiratory muscles are affected. Some insecticides currently in use, including those known as organophosphates (e.g. parathion), have a similar effect on insects, and can also cause harm to nervous and muscular system of humans who are overexposed to them.
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Allosteric regulation
Conformational changes by regulatory molecules inhibitors keeps enzyme in inactive form activators keeps enzyme in active form Conformational changes Allosteric regulation
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A B C D E F G A B C D E F G Metabolic pathways
enzyme 1 enzyme 3 enzyme 2 enzyme enzyme 4 enzyme 5 enzyme 6 Chemical reactions of life are organized in pathways divide chemical reaction into _________ small steps artifact of evolution ____ efficiency intermediate branching points control = _______________
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Whoa! All that going on in those little mitochondria!
Efficiency Organized _________________ of enzymes enzymes are embedded in membrane and arranged __________________________ _________ endergonic & exergonic reactions Whoa! All that going on in those little mitochondria!
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X A B C D E F G 4) Feedback Inhibition
Regulation & coordination of production _____________ is used by _______ step in pathway final product is _________________ of earlier step allosteric inhibitor of earlier enzyme feedback inhibition no unnecessary accumulation of product A B C D E F G enzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5 enzyme 6 X allosteric inhibitor of enzyme 1
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= _______________ Feedback mechanism
Feedback Inhibition threonine Example synthesis of amino acid, ___________________ from amino acid, ___________________ isoleucine becomes the __________________ inhibitor of the first step in the pathway as product accumulates it collides with enzyme more often than substrate does = _______________ Feedback mechanism isoleucine
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FeedBack loops negative-feedback-loops
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NEED MORE? Bozeman Science to the Rescue! Watch “Enzymes here:
