Intro Energy Cell Respiration 2

Cell Respiration - 1 All cells need energy to stay alive and maintain an ordered cellular environment. Cell growth, development and reproduction all require energy. Movement of materials through membranes often requires energy, as do intracellular movements. Cells obtain the energy to do work by oxidizing organic molecules, a process called cellular respiration*. Although many organic molecules can be oxidized, glucose, the main product of photosynthesis, is the primary f uel molecule for the cells of living organisms. Cell respiration pathways are catabolic – the end products have less energy than the reactants. Some of the energy released during cell respiration is heat energy; the rest is used to make molecules of A TP. * The term, cellular respiration, in some references is restricted to the aerobic respiratory pathways of glucose metabolism that occur in the mitochondria of eukaryotic organisms. It is used to describe all pathways involved in fuel metabolism here. All organisms, autotrophs and heterotrophs, must do cell respiration. Recall that organisms that do photosynthesis (or properly, manufacture their own fuel molecules) are called a utotrophs. H eterotrophs obtain their fuel molecules "pre-formed" by other organisms. Animals, fungi, many protists and many bacteria are heterotrophs. Plants and some protists are autotrophs, as are some bacteria, in particular, the cyanobacteria. The cell respiration processes of all organisms have common elements of metabolic pathways: • The chemical reactions of cell respiration involve metabolic pathways. • Each chemical reaction in the pathway is catalyzed by a specific enzyme. • The pathways of cell respiration are remarkably uniform in all organisms. • Eukaryotic organisms compartmentalize the respiratory reactions. • Respiration is regulated by feedback mechanisms at key enzyme points. The metabolic pathways of cell respiration vary depending on the type of organism, the enzymes the organism has, oxygen use, and what the final product molecule in the cell respiration process is. We will focus on the metabolism of glucose in cell respiration, but we shall also discuss how alternative fuel molecules fit into the cell respiration pathways. Most eukaryotic organisms are a erobic (oxygen requiring). In a erobic cellular respiration, which is the complete metabolism of glucose, electrons removed from glucose move down an electron transport system through a series of oxidation-reduction reactions to a final electron acceptor, o xygen, hence, the emphasis on oxygen in cell respiration. Most organisms are o bligate aerobes. They cannot survive without the oxygen needed for aerobic cell respiration.

Cell Respiration - 2 In complete aerobic respiration, glucose is broken down into water and carbon dioxide. This process requires oxygen. C6H12O6 + 6O2  6H2O + 6CO2 + 686 kcal (ATP + Heat) Not all cell respiration is aerobic. Organisms that do cell respiration without oxygen are said to be anaerobic. Fuel molecules can be oxidized without oxygen to yield smaller amounts of ATP. The f ermentations involve the partial breakdown of glucose without using oxygen. Many prokaryotes have a variety of fermentation pathways, using a number of different fuel molecules. The final electron acceptor for the fermentations is an o rganic molecule. In addition, if the final electron acceptor is an i norganic molecule other than oxygen, the process is called a naerobic respiration. All organisms do some type of anaerobic respiration or fermentation during times of oxygen deficit, although it may not be sufficient to sustain the organism's ATP needs. Some organisms are obligate anaerobes. They can not survive in the presence of oxygen. Other anaerobes are m etabolic anaerobes; they lack the enzymes needed to do aerobic cell respiration. Some organisms will survive nicely in the absence of oxygen but will do aerobic respiration when oxygen is available.

Cell Respiration - 3 Aerobic Cell Respiration - An Overview As with many metabolic processes, aerobic cell respiration has a number of stages (three or four depending on who is describing the process) and can be used to obtain energy from a number of fuel molecules. By convention, and because it is the primary fuel molecule for most cellular respiration, we use glucose as our fuel to illustrate the respiration pathway.

Glycolysis The initial stage of glucose metabolism, or cell respiration, is a process called glycolysis, which splits a glucose molecule into two molecules of pyruvate, a 3-carbon compound. Glycolysis occurs in the cytosol of the cell. What happens after glycolysis depends on the presence or absence of oxygen and/or the enzymes needed. • If oxygen is not available, or if the organism lacks enzymes needed for aerobic respiration, the pyruvate molecules will proceed with fermentations, or for some prokaryotes, anaerobic respiration, which we will discuss later. • If oxygen is available and the organism has the enzymes to do a erobic respiration, the pyruvate molecules will be oxidized in the next stages of aerobic respiration. During the second (and third) stages of a erobic respiration: • Pyruvate molecules are oxidized and lose a CO2. • The two-carbon molecules then enter the K rebs, or Citric Acid C ycle, where more oxidations occur, releasing two more CO2. The Krebs cycle occurs in the mitochondrial matrix.

Cell Respiration - 4 The final stage of aerobic respiration is the e lectron transport chain and the chemiosmotic synthesis of ATP. Since the energy to synthesize ATP is from the oxidation-reduction reactions, such synthesis is called o xidative phosphorylation. • Oxygen is the final electron acceptor for the oxidation-reductions that start with NADH in the electron transport system. • The electron transport system takes place in the inner membrane of the mitochondria. • When oxygen is available, as much as 38 ATP can be generated from one glucose molecule Cellular Respiration - The Pathways Glycolysis • Glucose is “activated” by two ATP-consuming reactions. The glucose molecule is phosphorylated in these reactions. The phosphorylated bonding sites are sufficiently unstable to start what is, from that point, a series of exergonic oxidations. • Glucose is then broken into two molecules of the 3-carbon compound, Pyruvate. • In addition: o Two molecules of NADH are produced o A net of two molecules of ATP are produced
(Four molecules of ATP are made during Glycolysis, but 2 molecules are consumed in activating the glucose) • Glycolysis always occurs in the cytosol of the cell. • Incidentally, Glycolysis is the most widespread metabolic pathway in living organisms, today and evolutionarily. The earliest prokaryotes probably had the glycolysis pathway.

Cell Respiration - 5 Glycolysis

Cell Respiration - 6 Summary

of

Glycolysis

Glucose + 2ATP + 2NAD+ + 2ADP + 2Pi --> 2 Pyruvate + 2NADH + 4ATP* * Net gain of 2ATP Inputs Glucose 2 ATP* 2 NA D+ 2 ADP + 2Pi Outputs 2 Pyruvate 2 NADH 4 ATP* * Therefore the net energy yield is 2 ATP

Notes: • The ATP generated is by s ubstrate-level phosphorylation

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All steps are catalyzed by specific enzymes Glycolysis occurs in the cytosol of the cell Glycolysis is the initial cell respiratory pathway of a ll eukaryotic organisms.

After Glycolysis Pyruvate is a critical intermediate in the cellular respiratory pathways. As stated, virtually all organisms do glycolysis. The respiratory pathways diverge at pyruvate. If oxygen is available, and the organism has the appropriate enzymes, pyruvate is oxidized and follows the aerobic respiratory pathway. In the absence of oxygen, pyruvate will be reduced in a fermentation pathway or the anaerobic respiratory pathway. Pyruvate is also an important intermediate in the use of fuel molecules other than glucose.

Cell Respiration - 7 Aerobic Respiration Pathway Aerobic Cellular Respiration is has two or three stages following glycolysis. (Some references consider the oxidation of pyruvate to be a part of the Krebs cycle; others a separate, preparatory step.) • Oxidation of Pyruvate to Acetyl-CoA • The Krebs (Citric Acid) Cycle • Electron Transport Chain and Oxidative phosphorylation Revisiting the Mitochondrion The aerobic respiration reactions occur within the m itochondria of the cell. Prior to discussing the Krebs cycle and electron transport, let's review the structure of the mitochondrion. Recall that the mitochondrion has an smooth outer membrane and a deeply folded inner membrane. The folds are called cristae. The internal space of the mitochondrion is called the matrix. The space between the outer membrane and the inner membrane is the intermembrane space.

The enzymes needed to do the Krebs cycle are located in the mitochondrial matrix or embedded in the inner membrane as integral proteins. The enzymes and electron carrier complex for electron transport in the respiratory chain are located in the inner membrane.

Cell Respiration - 8 Oxidation of Pyruvate to Form Acetyl-CoA The oxidation of pyruvate uses a multi-enzyme complex within the mitochondria that completes the three steps while retaining the intermediates within the complex. P yruvate dehydrogenase is among the larges enzymes known, composed of at least 60 polypeptide subunits. The two Pyruvate molecules are transported into the inner matrix of the mitochondria via facilitated diffusion where is undergoes o xidative decarboxylation within the pyruvate dehydrogenase complex. • CO2 is removed from pyruvate, producing a 2-carbon compound. • The 2-carbon fragment is oxidized releasing H+ to reduce NAD+ to NADH, leaving A cetyl • Acetyl combines with Co-enzyme A (formed from the B vitamin, pantothenic acid and added sulfur groups) to form A cetyl-CoA, which can enter the Krebs cycle.

Pyruvate dehydrogenase For one glucose molecule (two pyruvate molecules), we obtain: • 2 CO2 • 2 NADH • 2 Acetyl C0-A

Note: When the level of ATP is high in a cell, the cell can convert acetyl-CoA into lipid molecules that can be stored for later energy use. This is one way that excess calories, no matter the nutrient source, are converted to fat.

Cell Respiration - 9 The Krebs Cycle (Citric Acid or TCA Cycle) The Krebs cycle is a means to remove energy rich H+ (with its electrons) from the remnants of the original glucose molecule (or other fuel molecules). The H+ and electrons removed can subsequently be used to generate ATP in the electron transport chain via chemiosmosis. This is done via a series of oxidationreductions. The acids of the Krebs cycle under the right conditions (i.e., The Krebs Cycle) can be oxidized. They donate H+ and its electron to the appropriate energy transfer molecule. Once the hydrogen is removed, carbon can also be removed as the waste product, CO2. In addition, for each original glucose molecule, two ATP are produced in the Krebs cycle by s ubstrate-level phosphorylation, one for each acetyl Co-A molecule that enters the Krebs cycle. (Remember that the glucose molecule has already gone through glycolysis and been converted to two molecules of pyruvate in the cytoplasm prior to starting the Krebs cycle.) In biology, a cycle is a metabolic pathway that starts and ends with the same molecule. The Krebs cycle starts with Oxaloacetic acid (A 4-carbon acid), which is regenerated at the end of the cycle. O xaloacetic acid combines with A cetylCoA to begin the Krebs cycle. Most of the enzymes needed to do the Krebs cycle are located in the mitochondrial matrix. Two, succinate dehydrogenase and
ketodehydrogenase, are integral membrane proteins of the inner mitochondrial membrane.

Note: The acids in this process are ionized, and the naming convention is to use the suffix -ate. For example, oxaloacetic acid may be called oxaloacetate in the cycle. For each turn of the Krebs cycle we will get: • 2 CO2 • 1 ATP produced (by substrate phosphorylation) • 1 FADH2 • 3 NADH The Krebs cycle must turn two times to oxidize the two molecules of Acetyl-CoA that are what's left of the original glucose molecule. It should be noted, for preciseness, that a molecule of H2O is also consumed in the Krebs cycle. Don't worry about it.

Cell Respiration - 10 The Krebs Cycle

The Krebs cycle will turn t wo times for each glucose molecule, since glycolysis produces two pyruvate molecules. Therefore, for each glucose molecule that we start with, at the completion of the Krebs cycle's two turns, including the preparation step of pyruvate  acetyl we have: • 6 CO2 • 2 ATP • 2 FADH2 • 8 NADH For the curious, the enzymes of the Krebs cycle are: Citrate synthase Succinyl-CoA synthetase Aconitase Succinate dehydrogenase Isocitrate dehydrogenase Fumarase
-Ketodehydrogenase Malate dehydrogenase

Cell Respiration - 11 To provide an idea of the potential energy gained from the Krebs cycle, we can look at the change in free energy as the reactions of the Krebs cycle take place.

Special Note on Vitamins and the Krebs Cycle Several vitamins function as precursors to coenzymes and energy transfer molecules involved in the Krebs cycle as well as in nutrient interconversions so that fuel molecules other than glucose can be used in cell respiration. Here • • • • • •

are a few: Coenzyme A is made from pantothenic acid NAD is made from niacin FAD is made from riboflavin Cobalamin (B12) is needed for amino acid interconversion Biotin is used for conversion of fats for fuel molecules Pyroxidine (B6) is used for amino acid interconversion and converting glycogen to glucose • Thiamin is a coenzyme use for removing CO2 molecules

Cell Respiration - 12 Electron Transport Chain and ATP Synthesis by Chemiosmosis The molecules of the electron transport chain, also called the respiratory chain, and a protein complex, A TP Synthase, are found in the inner membrane of the mitochondria . • The molecules of the electron transport chain are a set of four large integral membrane protein complexes: N ADH-Q reductase, s uccinate reductase, c ytochrome c reductase and c ytochrome oxidase, the peripheral protein, cytochrome c , and the lipid, u biquinone (or Q ). • Electrons enter the respiratory chain from NADH and FADH2.

The Respiratory Chain

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Electrons travel down the electron transport chain by oxidation-reduction reactions releasing their energy in controlled bits. The redox reactions of the electron transport chain are used to move, by active transport, Hydrogen ions (H+) from the mitochondrial matrix through the inner membrane into the intermembrane space. Some of the carriers pick up both electrons and H+ and release the H+ on the opposite side of the membrane. Others move just electrons.

Electron Transport Chain

Cell Respiration - 13 •

The concentration of H+ in the intermembrane space establishes a concentration, pH and electrical gradient that has an inherent (potential) energy value. There can be as much as a 1000 X difference H+ concentration on the different sides of the mitochondrion inner membrane. The accumulated H+ ions, known as the p roton-motive force, diffuse through the channels of the ATP synthase protein complex back into the mitochondrial matrix. The protein complex of ATP synthase uses the exergonic flow of H+ ions to phosphorylate ADP, forming ATP in the mitochondrial matrix, a process called c hemiosmosis. Peter Mitchell won the 1978 Nobel prize in chemistry "for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory". ATP is synthesized in the thylakoid membranes of the chloroplast by a similar mechanism.

•

Each NADH that enters the ETS provides sufficient energy to synthesize 3 ATP molecules by chemiosmosis. FADH2 provides energy for 2 ATPs.

ATP Synthase

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Oxygen is required as the final electron (and Hydrogen) acceptor, producing water as the end product of aerobic cellular respiration as the H+ and epassed off the carriers combine with oxygen. (Recall that CO2 is also a product of aerobic cellular respiration.)

Certain poisons work by blocking electron transport. Rotenone blocks NADH. Cyanide and carbon monoxide block cytochrome c from reducing oxygen. Oligomycin blocks the flow of H+ through the ATP synthase pump.

Cell Respiration - 14 Summary of ATP production through the Electron Transport System 8 NADH  24 ATP 2 FADH2  4 ATP 2 NADH (moved in from cytosol)  4 ATP Total ATP production from ETS: 32 ATP Total ATP Yield from Aerobic Cellular Respiration ATP from Chemiosmosis using the Electron Transport System + • The potential energy of the electrons and H from each NADH produced in the Krebs cycle and the oxidation of pyruvate provides energy to produce a maximum of 3 ATP by chemiosmosis using the electron transport chain. o The 8 NADH yield energy for 24 ATP + • The electrons and H from each FADH2 produced in the Krebs cycle provides energy to produce a maximum of 2 ATP by chemiosmosis in the ETS. (FAD is a lower energy electron transfer molecule and enters the transport chain in mid-chain, rather than at the start.) o The 2 FADH2 yield energy for 4 ATP • The electrons and hydrogen from each NADH from Glycolysis provides energy to produce 2 ATP in the ETS. (The NADH molecules have to be transferred from the cytoplasm to the mitochondria.) o The 2 NADH yield energy for 4 ATP ATP from Substrate Phosphorylation • 2 ATP net gain are produced in Glycolysis • 2 ATP are produced in the Krebs cycle Total ATP = 36

The maximum ATP may not be realized, since the inner mitochondrial membrane is leaky to protons and some energy is used to move pyruvate from the cytoplasm into the mitochondrial matrix. Cells may get about .5 ATP less per reduced carrier that enters electron transport than the maximum.

Cell Respiration - 15 Aerobic (Cellular) Respiration Summary • The complete aerobic respiration of glucose requires four stages: o Glycolysis o Pyruvate Oxidation o The Krebs cycle o Electron transport phosphorylation • Oxygen is the final electron acceptor in the electron transport system The O2 combines with Hydrogen to form water • Carbon Dioxide (CO2) is released during aerobic respiration • As much as 36 ATP can be produced from each glucose molecule • Oxidation of pyruvate, the Krebs cycle and Electron transport occur in the mitochondria; G lycolysis occurs in the cytosol. • All steps are catalyzed by enzymes Generating Heat From Cell Respiration - Thermogenesis There are times when generating heat rather than ATP is desired. Organisms, such as bats, that experience torpor (a reduced metabolic state that results in lowered body temperature) need to increase body temperature rapidly when they wake from torpor. Heat generation requires separating the H+ proton flow from ATP synthase. Mitochondria in special fat containing cells (the "brown" fat) have a H+ "uncoupling" protein, t hermogenin, which moves protons through the membrane into the mitochondrial matrix bypassing the ATP synthase pump. Energy released by the oxidations generates heat instead. Plants also have uncoupling proteins for heat generation. Arum lilies attract carrion beetles and flies for pollination by exuding odors that smell like carrion. The voodoo lily increases the temperature of the flower so that the odors volatilize and disperse better. Skunk cabbage elevates its body temperature as much as 10 - 12° C above ambient air temperature for flowering.

Arum thermogenesis

Cell Respiration - 16 The Fermentations: Fate of Pyruvate in the Absence of Oxygen The overwhelming majority of living organisms must do aerobic cellular respiration to stay alive. Fermentations and anaerobic respiration pathways provide insufficient ATP to sustain life for most organisms. However, when oxygen is not available for aerobic cell respiration, eukaryotic organisms and some prokaryotes, will complete glucose metabolism with the fermentation reactions, which are essentially an extension of glycolysis. Some prokaryotes do a naerobic respiration.

For some prokaryotes and eukaryotes, fermentation is a way of life. Some lack the enzymes to do the Krebs cycle or oxidative phosphorylation; for others, oxygen is toxic. These are the strict (or obligate) anaerobes. Others, such as yeasts and E. coli are f acultative organisms. When oxygen is available, they do aerobic respiration. When oxygen is not, they perform a fermentation. NADH must be recycled constantly in cells. Like ATP, it cannot be stockpiled. NADH's oxidation reaction is highly spontaneous. NADH must use its electrons to reduce something and recover NAD+ for more glycolysis. However, NADH's very high energy electrons can be used to make ATP only in the presence of oxygen. In the fermentations the NADH electrons produced in glycolysis are used to reduce pyruvate to some other organic molecule, which becomes the final electron acceptor. No more ATP is obtained in the fermentation processes beyond the two ATP produced during the glycolysis pathway. However, in cells that normally do aerobic respiration, the rate of glycolysis increases when oxygen is unavailable, to produce as much ATP as possible. In

the Fermentations: • Organic molecules serve as the electron acceptors for NADH. • Among the Prokaryotes there are several different fermentation pathways. • However only two pathways are found in Eukaryotic organisms: Alcoholic Fermentation Lactic Acid Fermentation

Cell Respiration - 17 Details of the Fermentations • Pyruvate functions as the electron acceptor for the NADH produced in glycolysis. • NADH is used to reduce Pyruvate to some stable organic molecule, freeing the NAD+ (or regenerating NAD+) for the reduction step in glycolysis. • No additional ATP is produced. • Two fermentation pathways are common in eukaryotes. The fermentation pathways are genetically determined. Humans, for example, do lactic acid fermentation; yeasts do alcohol fermentation.

Anaerobic Electron Transport in Prokaryotes (Anaerobic Respiration) Some bacteria have an electron transport system but oxygen is not the final electron acceptor. An inorganic substance, such as a sulfur or nitrogen-containing molecule, becomes the final electron acceptor. Of note are the m ethanogens, a significant source of methane production on earth. They reduce CO2 to CH4 using hydrogen from a number of organic molecules, including some acids. The sulfur bacteria can reduce sulfates to hydrogen sulfide, and the first photosynthesis on earth oxidized H2S for its source of hydrogen rather than water. Some bacteria today still use H2S for photosynthesis. Nitrogen and iron molecules also provide reducing power for anaerobic respiration. These processes are studied in microbiology.

Cell Respiration - 18 Versatility of Metabolic Pathways – Alternative Fuel Molecules Fats, proteins and even nucleic acids can be utilized for fuel in cell respiration.

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Other carbohydrates  Glucose  Glycolysis Lipids  Glycerol and Fatty Acids o Glycerol  Glycolysis (Glyceraldehyde 3 Phosphate) o Fatty Acids  Acetyl  Krebs Cycle Alcohol  Acetyl  Krebs Cycle Proteins  Amino Acids All amino acids must be deaminated prior to being used for fuel. o Amino Acids  Pyruvate  Krebs Cycle o Amino Acids  Acetyl  Krebs Cycle o Amino Acids  Krebs Cycle o Amino Acids* **  Pyruvate  Glycolysis  Glucose * * The g lucogenic amino acids in this group are converted to pyruvate and can be metabolized "back" to glucose to provide glucose to brain and nervous system cells and developing red blood cells. Amino acids that are converted to acetyl are called ketogenic .

Cell Respiration - 19 Any c arbohydrate that can be digested will be converted to glucose. It's just a matter of time needed to digest and rate of absorption. Polysaccharides and disaccharides are digested to monosaccharides in the digestive tract. All monosaccharides absorbed are converted in the liver to glucose for use in glycolysis. Fats are energy rich. A gram of fat potentially can produce two times as much ATP as a gram of carbohydrate or protein.
oxidation, which occurs in the mitochondrial matrix, converts fatty acids to the 2-carbon acetyl.
oxidation uses one ATP, and produces one FADH2 and one NADH along with each acetyl Co-A formed. A 16-carbon fatty acid can produce 8 acetyl Co-A.


oxidation of fatty acids Most cells routinely use a mix of fats and carbohydrates for fuel. The brain, nerve cells and red blood cells, however, have an absolute glucose requirement; fatty acid fragments cannot normally cross the brain membrane barriers so that the brain does not use fats for fuel. The use of fatty acids for fuel is also a strictly aerobic process. All anaerobic respiration requires glucose. Two important places for alternative fuel molecules to enter our respiration pathway are pyruvate and acetyl-CoA. When we have insufficient glucose for our brain and nerve cells, any molecule that can be converted to pyruvate can ultimately be used to form glucose, although it is an energy consuming process to "reverse" glycolysis. However, the step from pyruvate to acetyl is not reversible. Fuel molecules that are converted to acetyl, or to acids that are a part of the Krebs cycle are not only unavailable for conversion to glucose, but are useful only in aerobic respiration.

Cell Respiration - 20 Acetyl is also a major point for the conversion of all excess fuel molecules to fats as well. If we have sufficient energy, acetyl need not enter the Krebs cycle and is diverted to the formation of fatty acids for adipose storage. This acetyl can come from any fuel molecule: glucose, fatty acids or amino acids. All excess calories consumed, no matter the source, will be converted to adipose. Nutrient inter-conversion adds versatility to metabolic pathways. Acids from the Krebs cycle can be used to synthesize some amino acids, and acetyl can be used to synthesize fatty acids.
-ketoglutarate is an intermediate for amino acid, purine and chlorophyll synthesis. About half the amino acids can be synthesized from different amino acids or from other acids in the cells. We maintain a m etabolic homeostasis or a pool of metabolic intermediates within our cells and tissues that remains constant so long as our diet provides the appropriate mix of basic nutrients.

During s tarvation or f asting, or when there is insufficient carbohydrate for energy needs, the body uses proteins from body tissues to supply fuel molecules to the brain, nerve cells and red blood cells. If fat reserves are diminished, protein from body tissue will supply metabolic needs in all cells and tissues. The body will literally degrade itself to maintain essential cell activity. When fat reserves are mobilized in response to insufficient calories or insufficient carbohydrate in the diet, some of the fatty acid fragments combine to form ketone bodies rather than acetyl. These ketone bodies enter into circulation. Muscle and some other tissues can use ketone bodies for fuel, and ketone bodies can provide energy to some brain cells. However, some ketone bodies contain carboxyl groups forming keto acids that can cause ketosis, a condition that lowers the pH of the blood and impairs health.

Cell Respiration - 21 Regulating Cell Respiration Cells regulate cell respiration just as they regulate other metabolic activities. Cells that are metabolically more active will do more cell respiration (and generally have more mitochondria) to provide the ATP needed. When activity drops, the rate of ATP formation likewise diminishes. Fuel molecules used in cell respiration are also regulated. In general: • When levels of carbohydrate are high, glucose is metabolized more than fats. o As levels of glucose fall, stored glycogen (in animals) will be converted to glucose. o When glucose supplies diminish, more fat is mobilized to supplement metabolic needs. • Protein will be removed from body tissues when carbohydrate is unavailable to provide glucose for brain and nerve cells. • When specific nutrients are high, biosynthesis pathways related to nutrient inter-conversion that would produce those nutrients are stopped. All excess calories are converted to fat. Fat to fat conversion is efficient, and any fat consumed not needed for structural or fuel purposes is readily converted to adipose for storage. Excess carbohydrate beyond the maximum glycogen stores is also converted to fat in an endergonic process. Some of the caloric value of the carbohydrate is lost in the conversion. Excess amino acids will be converted either to glucose, if carbohydrate reserves are low, or to adipose. Much of this excess nutrient conversion occurs in the respiratory pathway at acetyl. Just as we convert fatty acids to acetyl to "feed" the Krebs cycle, acetyl not needed for the Krebs cycle is readily converted to fat. The mechanisms for most of these regulations involve feedback inhibition/activation. The relative amounts of ATP/ADP, NADH, and some intermediates in the Krebs cycle regulate aerobic respiration rate by feedback. For example: • High ADP stimulates the enzyme, phosphofructokinase, that converts fructose 6-phosphate to fructose 1,6-bisphosphate, enhancing the rate of glycolysis. • High ATP levels inhibit the conversion of isocitrate to
-ketoglutarate in the Krebs cycle as well as inhibit phosphofructokinase. • Low citrate levels in the Krebs cycle also stimulate phosphofructokinase; high levels inhibit the enzyme. High citrate levels also promote conversion of fatty acids to acetyl. • High NADH inhibits the enzyme, pyruvate decarboxylase, the enzyme that oxidizes pyruvate to acetyl, stopping the Krebs cycle.

Cell Respiration - 22