Biochem 2 Metabolism Notes PDF

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Dr. Eric Taylor...

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Law of Conservation of Matter – Mass cannot be created or destroyed. It can only be converted from one form to another. à only physicists have the ability to smash atoms and destroy matter Metabolism– the process in which things are processed or chemically dealt with in cells in an organism to keep the organism alive, allow it to reproduce, and keep it healthy, etc. à Weight gain/loss is dictated by caloric intake and caloric burn. à Basal Metabolic Rate– what body normally uses Fat gene suggests a gene that codes for weight gain without much intake of calories. This is NOT true. We know this b/c of how many people died of starvation during WWII. à Rule of dieting—you didn’t put weight on overnight so you can’t take it off overnight. à You can’t gain weight if you don’t eat!

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Typically, many diets would suggest that if you take out carbohydrates (because they ultimately become fats) you will loose weight. That’s true, but it creates problems. à carbohydrates are necessary for the normal glucagon/ insulin balance à carbohydrates dictate how much metabolism comes about à if you don’t eat for a few days you use up all your glycogen storage. The body starts to breakdown fat. The breakdown of fat produces ketone bodies. à Ketone bodies are dumped into the blood and decrease blood pH and ultimately causes a decrease in the blood’s ability to bind oxygen. * The decrease in oxygen in the blood results in not enough oxygen to supply both the brain and the heart. The brain cuts off the supply of oxygen to the heart, which causes a person to pass out. à Ketoacidosis à cutting out carbs entirely creates an artificial state of diabetes. You can’t cut all fats either. There are some fats that are essential. à There are some fats that the brain must have. Nobody with any sense would cut out al the protein from their diet. à protein is absolutely necessary for the everything (immune system, hair, eyelashes, muscles, skin, etc.) Dieting is not so much cutting things out, but rather being reasonable about what you take in. Everything in moderation, nothing to excess. You have to have minerals and other nutrients, but even too much of a good thing can be bad. Weighing yourself every day is NOT a good idea: psychological torture à better to use a tape measure than a scale à there is a point in the menstrual cycle when women gain water weight (bloating). à weight will fluctuate day to day and at different times during the day à muscle is 2x as dense of fat; muscle takes up a little less space

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than fat à it is best to weight once a month at the same time during the same day of menstrual cycle when weight seems to be the lowest There are certain things that loosing is just not good à weight loss is an emergency signal to the brain that something is wrong. à psychologically and evolutionarily the brain doesn’t think weight loss is good *Slightly reduced diet is better than a crash diet (510% fewer calories than needed to mantian body weight) *Brains go crazy with crash diets *must eat 10x body weight in pounds of calories for women to maintain body weight (11x for men) *Reducing calorie intake by 10% will not fry out brain & you won’t feel hungry à weight loss will also be gradual You can’t gain weight if you haven’t eaten it. To do so otherwise is to violate the laws of physics!

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3ft x 4ft chart of the biochemical pathways! à pathways are color coded by which pathways apply to plants, animals, bacteria, all organisms, etc. à this chart is only the surface of what we actually know! Pathways– a group of chemical reactions that start at one point and end up at another point à every pathway has a purpose and fulfills a purpose for the cell Steps to learning pathways: 1.) what’s the pathways purpose? à what is it supposed to accomplish à what it’s for à what is it supposed to do for the cell or the organism 2.) how does it accomplish that? à look at the steps à what are the products and catalysts that carry out each step

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à each step has a catalyst 3.) how is this controlled? à without control a living cell won’t be living for very long; it will die à How are the enzymes are controlled? à allosteric enzymes, denaturation, inhibition à control takes place at the enzyme level à some enzymes are the committed step of a process à committed to synthesize all the way to the end à critically controlled step ***Learn what steps are controlled & regulated!!

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Carbohydrates are the MOST important in producing energy. à carbohydrates are the preferred class of molecules we use to make ATP energy à glucose is a carbohydrate à the brain is the sweet tooth – brain has craving for glucose b/c glucose is it’s primary energy source à sugar cane, wheat, rice, barely, corn, etc. are carbohydrates à most common, plentiful biomolecule around Lipids à broad class of molecules à not a functional classification but rather a physical classification due to solubility of fats à we can make a lot of ATP from metabolizing a fatty acid (3.5x more ATP from a fatty acid than a glucose molecule) *we use carbs as the primary source of energy producing molecule and NOT lipids b/c it is the most plentiful molecule around

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à peanuts are the closest crop to a “fat” crop à cellulose is made of a form of glucose; cellulose is the plant form of glucose storage *cellulose is carbohydrate and a polymer of glucose Proteins à can be used as an energy source – happens when more protein is taken in than is needed for a certain day à the amine group that makes the protein an alpha amino acid is removed. The amino group becomes ammonia, which is highly poisonous. à ammonia is transported to the liver in the form of the amino acid glutamine. The R-group of glutamine is converted to urea. *urea is a non-poisonous form of ammonia that is excreted during urination *this is how the amine group that isn’t needed is gotten rid of *the carbon skeleton that is left behind will be converted to a carbohydrate (glycolysis) a ketone body (TCA cycle) à there is NO way of storing proteins (unlike fats and carbohydrates) *the closest humans come to storing proteins is skeletal muscle *skeletal muscle can be broken down during starvation Nucleic Acids are the least important in producing energy. à have no practical value as an ATP-energy producing source *the pyrimidines can be broken down into succinyl derivatives that lead into the TCA cycle *purines are excreted by uric acid *uric acid build up causes crystal deposits in joints known as gout

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Lipids generate the MOST ATP! à nothing trumps the lipids for ATP yield!

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FIGURE 17.4 Energy relationships between the pathways of catabolism and anabolism. Oxidative, exergonic pathways of catabolism release free energy and reducing power that are captured in the form of ATP and NADPH, respectively. Anabolic processes are endergonic, consuming chemical energy in the form of ATP and using NADPH as a source of high energy electrons for reductive purposes. Energy-yielding nutrients (fats, carbs, proteins) are broken down through catabolism. Catabolism is an oxidative/ exergonic process that gives rise to ATP and NADPH chemical energy. àThe chemical energy created by catabolism is used by anabolic process. Catabolism– oxidative or exergonic process that breaks down larger molecules into smaller molecules Anabolism – builds much more complicated molecules (polymers). Uses the energy products from catabolism; requires energy input; reductive process

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à the amino acids from catabolism can be used to build body proteins (hair, eye lashes, triceps, etc.) à requires energy input Nucleic acids can be synthesized from scratch, almost atom by atom, but it is EXPENSIVE. à Tons of ATP energy is burned making DNA/RNA! Energy is important in biochemistry. Wars are fought over energy. Nothing happens without energy. Biochemistry reactions are fueled by ATP. Some cases ATP is being made. Other cases ATP is being used to make a reaction occur. à even in catabolic reactions (where ATP is being made) often requires an initial input of ATP energy to get the reaction going *if you want to make money, you got to spend some first. It takes 30 ATP molecules to make 1 cholesterol molecule. à little kids are always hungry because they are constantly growing and making new cells; they have a high energy demand. Many times catabolic processes, in addition to making ATP, will have side molecules left over that become precursors. à pyruvate and lactate are precursors

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There are two molecules in biochemistry that will be seen over and over again that are reducing power. They are the major results of some pathways, specially the TCA cycle and beta oxidation. TCA cycle and beta oxidation don’t make ATP. The reducing power is what’s important. à The reducing power translates to ATP via the electron transport chain à NADPH is a molecule that arises in the pentose-phosphate pathway & is used to carry out reducing reactions in anabolic processes *the proton used to make deoxyribose comes from NADPH à NADH is typically associated with catabolic processes à NADPH should always have an H+ added to the side b/c there is a free H+ Oxidation– the removal of electrons and H+ There are other processes with an oxidized precursor and though some biosynthetic reactions the precursor is reduced to get the reduced form. Electrons

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and H+ are removed from the molecule and put on the reduced form. --This is how DNA and cholesterol are made

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Pathways consist of sequential steps. Enzymes may be separate, form a multienzyme complex, or be part of a membrane-bound system. àmulti-enzyme complexes are more common than once thought. The fatty acid synthesis complex is utilized to take Acetyl CoA and build a long chain fatty acid. à example of a multi-enzyme complex à about 7 enzymes and proteins associated with the fatty acid synthesis complex *enzymes carry out 7 different processes to create a fatty acid molecule *act as a single unit Membrane bound system of enzyme à Electron transport à ER & Golgi also have membrane bound systems

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Compartmentalization is one of the ways to control metabolic processes (catabolic and anabolic) à There are many many reactions that go opposite to each other. Ex: glucoseà pyruvate and pyruvate à glucose *futile cycle— opposite reactions cancel each other out *there are controls in place to prevent futile cycles à different enzymes do different things to control each reaction *there are enzymes that make pyruvate from glucose that are NOT active in the reverse reaction *gluconeogenesis– the synthesis of glucose à compartmentalization is another way to control enzyme processes à reverse reactions take place in different areas of the cell *Ex: fatty acid synthesis takes place in the cytosol while breakdown takes down in mitochondria Organ specialization is just another level of compartmentalization.

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à Ex: blood glucose levels must be maintained (if blood glucose levels fall you will pass out). à When blood glucose levels fall due to not eating the liver takes over and starts pumping glucose into blood stream from its glycogen stores to maintain blood glucose levels for the brain. *No other tissue has to do this! Just the liver. It does it at the command of the brain through hormones.

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Functions of metabolism: 1.) make ATP à need ATP to function 2.) synthesis of reducing power àNADH & FADH2 are very instrumental in electron transport leading to the production of more ATP 3.) synthesis of building blocks à biological systems obey all the laws of chemistry and physics (NO EXCEPTIONS), including the second law of thermodynamics *2nd Law of Thermodynamics– entropy; the universe tends towards chaos à Things break down naturally and must be repaired. *Things need to be built and repaired, more so when growing. à Building blocks are very instrumental.

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à Not only does metabolism make ATP but it breaks down things to make building blocks (amino acids, glucose, hyaluronic acid, etc.) 4.) catabolic and anabolic mechanisms are distinct and separated which avoids futile cycles à pathways can be separated by covalent modification (phosphorylation/ dephosphorylation, etc.), compartmentalization, or different catalysts Ex: organ specialization NO one function of metabolism is more important than the other!

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3.) covalent modification a.) posphorylation/ dephosphorylation à important process in regulating glycogen processing b.) adenylation/ deadenylation c.) proteolytic cleavage à most common place to see this is in digestive enzymes (pepsin, chymotrypsin, trypsin, carboxypeptidase A, ribonuclease) *these enzymes are secreted into a lumen (like the intestines) *many of these enzymes come out as a proenzyme and need to be processed to remove a fragment to expose it’s active site to become active *pepsin becomes hydrolyzed and activated at pH 5 (even though the stomach acid has a pH of 2) *pepsin has a bunch of amine groups that active like a lid on the active site à H+ from the stomach acid protonate al the amine groups and make them charged which causes a repulsion from the active site & exposes the active site

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4.) hormonal controls à in many cases trigger other processes like covalent modifications a.) insulin/glucagon

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5.) pathways– a sequence of reactions that have a particualr end point à pathways are important to the cell 6.) clustering of enzymes à enzymes can be grouped together, which can speed up the process b/c diffusion doesn’t take as long if enzymes are right up against each other à enzymes can be unlinked and proximate (in the same area i.e the cytosol or a specific organelle) à enzymes can be bound in multi-enzyme complexes *Ex: pyruvate dehydrogenase complex, fatty acid synthetase complex à enzymes can also be membrane bound, like in electron transport (in the matrix side of the inner mitochondrial membrane) 7.) there are key control points that are important in regulating metabolism à glucose-6-phosphate: the first result of the action of hexokinase/glucokinase activity on glucose

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*glucose-6-phosphate activates the molecule so that it can be used *glucose-6-phosphate doesn’t have to go through glycolysis to become pyruvate; it can be shunted off into the pentose-phosphate pathway to make ribose-phosphate for nucleic acid synthesis à Acetyl CoA is a major crosswords for a wide range of reaction decisions. *can go into several different anabolic and catabolic processes 8.) key metabolic junctions à where key control points are found

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ATP is formed via photosynthesis in photosynthetic cells or via catabolism is heterotrophic cells.

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Principle players in energy transfer and regulatory processes in cells: ATP, ADP, AMP. ATP is a molecule that offers a number of advantages that are ideally suited for a molecule that carries a lot of energy. à unstable *the molecule wants to tear the phosphates away from each other à can’t bottle it and come back a day later to find much of it left *ATP is hydrolyzed in solution at pH 7 very easily à must make ATP as you go à ATP can’t be stored à Triphosphate: there are 3 orthophosphate (alpha, beta, gamma) groups on ATP (-4 charge on molecule à extremely unstable molecule!) *4 negative charges on the phosphate groups à doesn’t have many resonance structures to distribute the charge around

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*resonance is a means of stabilizing a molecule à there is a lot of energy released when ATP is hydrolyzed to ADP ADP has a -3 charge à has a few more resonance structures so it is a little more stable than ATP à a lot more stable in solution AMP has a -2 charge à very stable molecule à signals energy deficit à any biological process that results in the production of AMP as product is a message to the cell that energy is becoming scarce à message to the cell that energy is becoming scarce à often an allosteric activator of certain enzymes à make enzymes go “quicker” b/c those enzymes are involved in making ATP

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Phosphoenolpyruvate (PEP) contains a lot of energy à one of the results of the processing of glucose in glycolysis à one of the molecules used to make an ATP molecule in glycolysis Creatine phosphate à involved in muscles, like skeletal muscles or heart muscles à sort of like a battery reserve of energy *can be used to regenerate ATP real quick from ADP 1,3-Bisphosphoglycerate (1,3-BPG) à another molecule that pops up in glycolysis à has two phosphate groups (one at each end) à also used to make an ATP molecule in glycolysis à has a hefty bounce of energy

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The two major fuels for ATP synthesis in animal cells are glucose and fatty acids. à glucose is the most important b/c it is the most abundant in the enviornment *it has different forms, but it is still the most abundant à the most common form of glucose is cellulose (found in plants) Every animal aside from animals and meat-eaters have evolved to eat and digest grass and stuff. à we can’t digest plants with cellulose but we can digest plants with starch *starch has 𝝰-1,4-glycosidic linkage which we can digest *cellulose has β-1,4-glycosidic linkages which we cannot digest b/c we lack the necessary enzymes Fatty acids are an important energy molecules à a bunch of ATP can be made from fatty acids

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à during starvation body fat can be broken down for energy

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Fatsà fatty acids + glycerol à Acetyl CoA à CO2 + reducing power à acetyl CoA enters the TCA cycle and produces CO2 and a lot of reducing power to make ATP à in the process O2 must be consumed b/c there are a lot of H+ and electrons released à we breathe oxygen to get rid of electrons and protons à Oxygen, next to fluorine, is the best electron sink in this universe à Oxidative phosphorylation—the process where we use the energy that was embodied in the reducing power of the H+ and electron flow to make ATP *the flow of H+ and electrons does not make ATP. ATP is already make; it just allows ATP to be released from the enzyme Polysaccharides à glucose + other sugars à Acetyl CoA à fructose, galactose, some mannose, ribose are the important monosaccharides in addition to glucose à many monosaccharides can be biochemically converted to glucose and can be used to get Acetyl CoA

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à sugars become pyruvate in the cytosol. Pyruvate enters the mitochondria where it is acted on by the pyruvate dehydrogenase complex to make Acetyl CoA. *Acetyl CoA then enters the TCA cycle. *Once you have Acetyl CoA, the process is the same. Proteins à amino acids àAAs have 3 classifications: 1.) glucogenic– amino acids that can be converted to glucose-type intermediate à ex: alanine *if you de-aminate alanine you will make pyruvate which can ultimately be converted to Acetyl CoA and enter the TCA cycle 2.) ketogenic—gives a ketone-body type structure for the TCA cycle that goes directly to Acetyl CoA 3.) Either-or –can be converted to a glucose intermediate or a ketone body intermediate à The first thing that has to happen is that the amine group has to be removed. Once you have the carbon skeleton, it is fair game for a catabolic process to produce ATP energy. *this happens to have dietary protein that is taken in that is in excess of what body is needed àBody muscle protein will go that way only if it is degraded. That can happen if the muscle is particularly old. Some proteins have carbohydrate tags on them that is thought to code for the age of the protein. As the carbohydrate is hydrolyzed off, it indicates the age of the protein. At some point the protein is susceptible to degradation. If the muscle is damaged and injured the dead cells will be processed this way. Generally speaking, there are processes that stop the breakdown of muscle. à starvation and diabetes (I &II) are examples when proteolysis of body ...