7: Cellular Respiration Flashcards
Energy in Living Systems, Glycolysis, Oxidation of Pyruvate and the Citric Acid Cycle, Oxidative Phosphorylation, Metabolism without Oxygen, Connections of Carbohydrate, Protein, and Lipid Metabolism, Regulation of Cellular Respiration
1
Q
What is chemiosmosis?
A
The process in which there is a production of adenosine triphosphate (ATP) in cellular metabolism by the involvement of a proton gradient across a membrane.
2
Q
What is dephosphorylation?
A
Removal of a phosphate group from a molecule.
3
Q
What is oxidative phosphorylation?
A
Production of ATP using the process of chemiosmosis and oxygen.
4
Q
What is phosphorylation?
A
Addition of a high-energy phosphate to a compound, usually a metabolic intermediate, a protein, or ADP.
5
Q
What is a redox reaction?
A
Chemical reaction that consists of the coupling of an oxidation reaction and a reduction reaction.
6
Q
What is substrate-level phosphorylation?
A
Production of ATP from ADP using the excess energy from a chemical reaction and a phosphate group from a reactant.
7
Q
How do redox reactions affect energy?
A
An oxidation reaction removes an electron from an atom in a compound, and a reduction reaction adds the electron to another compound. Oxidation results in a decrease in potential energy in the oxidized compound, and reduction results in an increase in the potential energy of the reduced compound. Most of the energy stored in atoms and used to fuel cell functions is in the form of high-energy electrons.
8
Q
What is an electron carrier?
A
Compounds which bind and carry high-energy electrons between compounds in pathways. These compounds can be easily reduced or oxidized.
9
Q
Where is NAD derived from?
A
Nicotinamide adenine dinucleotide (NAD) is derived from vitamin B3 (niacin).
10
Q
What is the difference between NAD+ and NADH?
A
NAD+ is the oxidized form and NADH is the reduced form. NADH has accepted two electrons and a proton.
11
Q
What is the general equation for converting NAD+ to NADH?
A
NAD+ can accept electrons from an organic molecule according to the general equation:
RH (reducing agent) + NAD+ (oxidizing agent) -> NADH (reduced) + R+ (oxidized)
12
Q
Where is FAD derived from?
A
Flavin adenine dinucleotide (FAD+) is derived from B2 (riboflavin). Its reduced form is FADH2.
13
Q
What is NADP?
A
NADP contains an extra phosphate group.
14
Q
Where are NAD and FAD used?
A
NAD+ and FAD+ are extensively used in energy extraction from sugars, and NADP plays an important role in anabolic reactions and photosynthesis.
15
Q
How do phosphate groups store energy?
A
The addition of a phosphate group to a molecule requires energy. Phosphate groups are negatively charged and repel one another when arranged in series, such as in ADP and ATP. This makes them inherently unstable.
16
Q
Where does the energy to produce ATP come from?
A
The energy to produce ATP comes from the metabolism of glucose. ATP is a direct link between the limited set of exergonic pathways of glucose catabolism and the multitude of endergonic pathways that power living cells.
17
Q
Where does chemiosmosis take place?
A
Chemiosmosis occurs in mitochondria of eukaryotic cells, and in the plasma membrane of prokaryotic cells.
18
Q
What is the purpose of chemiosmosis?
A
Chemiosmosis is used to generate 90% of the ATP made during glucose catabolism, and is the method used in the light reactions of photosynthesis to harness the energy of sunlight.
19
Q
In what ways can oxidative phosphorylation be impacted?
A
In type 2 diabetes, the oxidation efficiency of NADH is reduced, impacting oxidative phosphorylation.
20
Q
What is aerobic respiration?
A
The process by which organisms convert energy in the presence of oxygen.
21
Q
What is an anaerobic process?
A
A process that does not use oxygen.
22
Q
What is glycolysis?
A
The process of breaking glucose into two three-carbon molecules with the production of ATP and NADH.
23
Q
What is an isomerase?
A
An enzyme that converts a molecule into its isomer.
24
Q
What is pyruvate?
A
A three-carbon sugar that can be decarboxylated and oxidized to make acetyl CoA, which enters the citric acid cycle under aerobic conditions; it is the end product of glycolysis.
25
What is the purpose of glycolysis?
Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism. Nearly all living organisms carry out glycolysis as part of their metabolism.
26
Is glycolysis aerobic or anaerobic?
This process is anaerobic.
27
Where does glycolysis take place?
It takes place in the cytoplasm of both prokaryotic and eukaryotic cells.
28
How does glucose enter heterotrophic cells?
Glucose enters heterotrophic cells in two ways. One is through secondary active transport which takes place against the glucose concentration gradient. The other uses a group of integral proteins called GLUT proteins, or glucose transporter proteins, which assist in the facilitated diffusion of glucose.
29
What are the inputs and outputs of glycolysis?
Glycolysis begins with the six carbon ring-shaped structure of a single glucose molecule, and ends with two molecules of a three-carbon sugar called pyruvate.
30
What are the phases of glycolysis?
Glycolysis consists of two distinct phases. The first part of the pathway traps the glucose molecule in the cell and uses energy to modify it so that it can be split evenly into the two pyruvate molecules. The second part extracts energy from the molecules and stores it as ATP and NADH.
31
What are the (energy-requiring) steps of the first half of glycolysis?
* The first step of glycolysis is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates using ATP, producing glucose-6-phosphate, which is more reactive than glucose. This molecule will no longer interact with GLUT proteins, and cannot cross the membrane to leave the cell (because of the negative charge of the phosphate).
* In step 2, an isomerase converts glucose-6-phosphate into fructose-6-phosphate.
* In step 3, fructose-1,6-biphosphate is produced, catalyzed by phosphofructokinase using ATP. This enzyme is rate-limiting, more active when the concentration of ADP is high.
* In step 4, aldolase catabolizes this intermediate into two three-carbon isomers: dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
* In step 5, an isomerase transforms the dihydroxyacetone-phosphate into glyceraldehyde-3-phosphate.
32
What are the (energy-releasing) steps of the second half of glycolysis?
* In step 6, the sugars are oxidized by NAD+ (producing NADH), and phosphorylated to produce 1,3-bisphosphoglycerate (which does not occur by ATP, rather an independent phosphate molecule). This is a limiting factor for this pathway, which depends on the availability of NAD+ (and hence NADH and an oxidizing agent such as oxygen).
* In step 7, phosphoglycerate kinase catalyzes 1,3-bisphosphoglycerate to donate a phosphate to ADP, forming ATP (substrate-level phosphorylation). A carbonyl group on the molecule is oxidized to a carboxyl group, forming 3-phosphoglycerate.
* In step 8, a mutase (which is a kind of isomerase) moves the phosphate from the third carbon to the second carbon, producing 2-phosphoglycerate.
* In step 9, enolase catalyzes a dehydration reaction, resulting in the formation of a double bond that increases the potential energy in the remaining phosphate bond and produces phosphoenolpyruvate (PEP).
* The 10th and final step is catalyzed by pyruvate kinase, which results in the creation of an additional ATP molecule by substrate-level phosphorylation and the compound pyruvic acid (or its salt form, pyruvate).
33
How many ATP and NADH molecules are produced during glycolysis?
A net gain of two ATP molecules and two NADH molecules are produced, with an investment of two ATP molecules.
34
What is acetyl CoA?
Combination of an acetyl group derived from pyruvic acid and coenzyme A, which is made from pantothenic acid (a *B*-group vitamin).
35
What is the citric acid cycle?
A series of enzyme-catalyzed chemical reactions of central importance in all living cells.
36
What are some other names of the citric acid cycle?
The Krebs cycle and the TCA cycle.
37
Why is the Krebs cycle so named?
The Krebs cycle is named after Hans Krebs who first identified the steps in the pathway in the 1930s in pigeon flight muscles.
38
Why is the TCA cycle so named?
The TCA cycle is named after the group name for citric acid, tricarboxylic acid (TCA).
39
What happens to the pyruvate produced by glycolysis?
At the end of glycolysis, pyruvate is transported into mitochondria, the sites of cellular respiration. There, pyruvate will be transformed into an acetyl group that will be picked up and activated by a carrier compound called CoA.
40
What is the purpose of acetyl CoA?
Acetyl CoA can be used in many ways, but its major function is to deliver the acetyl group derived from pyruvate to the next stage of the pathway in glucose catabolism.
41
What are the steps of the breakdown of pyruvate?
* In the first step, a carboxyl group is removed from pyruvate, which releases a molecule of CO2. This results in a two-carbon hydroxyethyl group bound to the enzyme pyruvate dehydrogenase.
* In step 2, the hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+ -\> NADH.
* In step 3, the enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA.
42
How does acetyl CoA work?
In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups.
43
Where does the citric acid cycle take place?
The citric acid cycle takes place in the mitochondrial matrix. All but one of the enzymes are soluble (succinate dehydrogenase is found in the inner membrane of the mitochondrion).
44
What are some characteristics of the citric acid cycle?
The citric acid cycle is a closed loop, where the last step regenerates the compound used as input to the first. They are a series of redox, dehydration, hydration, and decarboxylation reactions that produce 2 CO2, 1 GTP / ATP, and reduced forms of NADH and FADH2. This pathway is aerobic, because the NADH and FADH2 transfer their electrons to the next pathway in the system, which uses oxygen. The cycle produces very little ATP directly, and does not directly consume oxygen.
45
What are the steps of the citric acid cycle?
* In step 1, the acetyl group of acetyl CoA combines with oxaloacetate to form citrate. The CoA is bound to a sulfhydryl group (-SH) and diffuses away to combine with another acetyl group. This step is irreversible because it is highly exergonic. This reaction is controlled by negative feedback of the presence of ATP (more ATP, less reaction).
* In step 2, citrate is converted into isocitrate by the loss and re-gain of one H2O.
* In step 3, isocitrate is oxidized by NAD+ to produce alpha-ketoglutarate, CO2, and two electrons, which reduce NAD+ to NADH. This step is also regulated by negative feedback from ATP and NADH, with a positive effect of ADP.
* In step 4, oxidation and decarboxylation also occurs, producing NADH and CO2, and with an input of SH-CoA, forms succinyl CoA. The enzyme that catalyzes step 4 is regulated by feedback inhibition of ATP, succinyl CoA, and NADH.
* In step 5, a phosphate group is substituted for CoA, forming a high-energy bond which is used in substrate-level phosphorylation to form either GTP or ATP. Two forms of the enzyme (isoenzymes) are used depending on the type of animal tissue. One form is used in tissue which uses large amounts of ATP such as heart and skeletal muscle, the other in tissue that has a high number of anabolic pathways, such as liver, which uses GTP.
* In step 6, dehydration occurs, converting succinate to fumarate, transferring two hydrogen atoms to FAD ⇒ FADH2. The energy contained in the electrons of these atoms is insufficient to reduce NAD+, but adequate to reduce FAD. Unlike NADH, this carrier remains attached to the enzyme and transfers the electrons to the electron transport chain directly. This is made possible by the localization of the enzyme catalyzing this step inside the inner membrane of the mitochondrion.
* In step 7, fumarate is hydrolyzed into malate.
* In the 8th and final step, malate is oxidized, producing NADH / H+ and oxaloacetate.
46
What are the inputs and outputs of the citric acid cycle?
All six carbon atoms from glucose are eventually incorporated into the citric acid cycle. Each turn produces three NADH and one FADH2. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. One GTP or ATP is also made in each cycle. Several of these intermediates are precursors to the synthesis of non-essential amino acids. The cycle is amphibolic (both catabolic and anabolic). Amino acids may enter the citric acid cycle if there are excess amino acids in a cell, or if the body is in a state of starvation. Each amino acid must have its amino group removed prior to entry into the pathway. The lipids that are connected to the glucose pathways are cholesterol and triglycerides.
47
What is (F1F0) ATP synthase?
A membrane-embedded protein complex that adds a phosphate to ADP with energy from protons diffusing through it.
48
What is a prosthetic group?
A molecule bound to a protein that facilitates the function of the protein. They may be organic or inorganic, but are non-peptide.
49
What is ubiquinone?
A soluble electron transporter in the electron transport chain that connects the first or second complex to the third.
50
What is the electron transport chain?
A series of protein complexes that transfer electrons from electron donors to electron acceptors via redox reactions, and couples this electron transfer with the transfer of protons (H+ ions) across a membrane.
51
How many complexes are in the electron transport chain?
There are four protein complexes in the electron transport chain.
52
What are some characteristics of the complex I in the electron transport chain?
The first complex is composed of flavin mononucleotide (FMN) and an iron-sulfur (Fe-S)-containing protein. FMN, which is derived from vitamin B2 / riboflavin, is one of several prosthetic groups / cofactors in the electron transport chain. The enzyme in complex I is NADH dehydrogenase, a very large protein containing 45 amino acid chains. Complex I pumps 4 hydrogen ions across the membrane into the mitochondrial intermembrane space, establishing a hydrogen ion gradient.
53
What are some characteristics of the ubiquinone and complex II in the electron transport chain?
Complex II directly receives FADH2, which does not pass through complex I. Ubiquinone (Q) connects the first and second complexes to the third. Q is lipid soluble and freely moves throughout the inner membrane. QH2 (reduced Q) receives its electrons from NADH in complex I and from FADH2, and delivers them to complex III. The FADH2 electrons, by bypassing complex I, contribute to fewer ATP molecules produced.
54
What are some characteristics of the complex III in the electron transport chain?
Complex III is called cytochrome oxidoreductase, and is composed of cytochrome b, an Fe-S protein, Rieske center (2Fe-2S center), and cytochrome c proteins. They have a prosthetic group of heme (similar to the heme in hemoglobin, but which carries electrons rather than oxygen). The iron at its core is thus reduced and oxidized as it passes electrons, fluctuating between Fe++ and Fe+++. Cytochrome c carries electrons to complex IV, and accepts electrons from Q. Cytochrome c can only accept one electron at a time, in contrast to the two that Q can accept.
55
What are some characteristics of the complex IV in the electron transport chain?
Complex IV is composed of cytochrome proteins c, a, and a3. It contains two heme groups (one in each of in a and a3), and three copper ions (a pair of CuA and one CuB in a3). The cytochromes hold an oxygen molecule very tightly between the iron and copper ions until the oxygen is completely reduced. Then it bonds to hydrogen to form water from the surrounding medium. The removal of the hydrogen ions from the system contributes to the ion gradient used in the process of chemiosmosis.
56
How does chemiosmosis work?
Chemiosmosis uses ATP synthase (a membrane protein / ion channel) to allow hydrogen ions down its concentration gradient back into the matrix, and acts as a generator, turning and facilitating the addition of an inorganic phosphate to ADP, forming ATP, using the potential energy of the hydrogen ion gradient.
57
How many hydrogen ions can be pumped across membranes by the electron transport chain?
The number of hydrogen ions pumped through the membrane by the electron transport chain varies between species.
58
How many electrons can FAD shuttle compared to NAD and where is it used?
FAD+ can shuttle fewer electrons than NAD+, and so generates fewer ATP molecules. FAD+ is used more heavily than NAD+ in the brain.
59
How are the intermediates used in the glucose catabolism pathways?
Intermediates in these pathways are used for other purposes, and sugars other than glucose may be fed in the glycolytic pathway. The five-carbon sugars that form nucleic acids, some nonessential amino acids, lipids, cholesterol, and triglycerides are made from these intermediates in these pathways. Amino acids and triglycerides are also broken down for energy by these pathways. In living systems, these pathways extract about 34% of the energy contained in glucose.
60
Where is NAD+ used?
NAD+ is used more heavily than FAD+ in the liver.
61
How much energy is lost by electrons in the electron transport chain?
Electrons lose energy as they pass through the electron transport chain, from about 60kcal/mol of NADH or 45kcal/mol of FADH2 to about 0kcal/mol of water.
62
What is fermentation?
Process of regenerating NAD+ with either an inorganic or organic compound serving as the final electron acceptor; occurs in the absence of oxygen.
63
Where does lactic acid fermentation occur?
Lactic acid fermentation is a fermentation reaction that occurs in some bacteria and animal cells, such as muscle cells. In muscles, lactic acid accumulation must be removed by the blood circulation and the lactate brought to the liver for further metabolism. Once the lactic acid has been circulated to the liver, it can be reconverted into pyruvic acid and further catabolized for energy.
64
Which compounds are involved in lactic acid fermentation?
The chemical reactants of lactic acid are: pyruvic acid + NADH + H+ ⇒ lactic acid + NAD+. The enzyme used in this reaction is lactate dehydrogenase (LDH).
65
How does ethanol fermentation work?
The first chemical reaction is: pyruvic acid ⇒ CO2 + acetaldehyde + NADH ⇒ ethanol + NAD+. The first reaction is catalyzed by pyruvate decarboxylase, a cytoplasmic enzyme, with a coenzyme of thiamine pyrophosphate (TPP, derived from vitamin B1/thiamine). A carboxyl group is removed from pyruvic acid, releasing CO2, and producing acetaldehyde. The second reaction is catalyzed by alcohol dehydrogenase to oxidize NADH to NAD+ and reduce acetaldehyde to ethanol.
66
What does fermentation of pyruvic acid produce?
The fermentation of pyruvic acid by yeast produces the ethanol found in alcoholic beverages. Ethanol tolerance of yeast is variable, ranging from about 5 percent to 21 percent, depending on the yeast strain and environmental conditions.
67
Are prokaryotes aerobic or anaerobic?
Some prokaryotes are facultatively anaerobic, and so can switch between aerobic and anaerobic respiration depending on the availability of oxygen. Other prokaryotes are obligate anaerobes, and the presence of oxygen is lethally toxic to them.
68
What does fermentation produce?
All forms of fermentation except lactic acid produce gas. The production of particular types of gas is used as an indicator of the fermentation of specific carbohydrates, which plays a role in the laboratory identification of the bacteria. Various methods of fermentation are used by assorted organisms to ensure an adequate supply of NAD+ for the sixth step in glycolysis. Fermentation frequently accounts for any increased acidity in a cell, however the products of fermentation do not typically accumulate in cells.
69
How is glycogen produced and consumed by animals?
When ATP is available, excess glucose is stored as glycogen. It is made and stored in both liver and muscle. This allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into glucose-1-phosphate and glucose-6-phosphate in both muscle and liver cells, and this product enters the glycolytic pathway.
70
What is sucrose?
A disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage.
71
What is fructose?
One of the three dietary monosaccharides, along with glucose and galactose, which is absorbed directly into the bloodstream during digestion. The catabolism of fructose produces the same number of ATP molecules as glucose.
72
What is galactose?
One of the monosaccharides in the disaccharide lactose. The catabolism of galactose produces the same number of ATP molecules as glucose.
73
How is urea produced?
In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. The ammonia molecules may come from amino acids, on removal prior to entry into the citric acid cycle. Urea is the principal waste product in mammals produced from the nitrogen originating in amino acids, and it leaves the body in urine.
74
What is cholesterol?
A lipid that contributes to cell membrane flexibility and is a precursor of steroid hormones.
75
Is the synthesis of cholesterol a cycle?
The synthesis of cholesterol starts with acetyl groups and proceeds in only one direction. The process cannot be reversed.
76
What is a triglyceride?
A form of long-term storage in animals. They are made of glycerol and three fatty acids.
77
How are triglycerides used in the glucose catabolism pathways?
Triglycerides can be both anabolized and catabolized in certain steps of the glucose catabolism pathways.
78
How are fatty acids incorporated into the citric acid cycle?
Animals can make most of the fatty acids they need. Fatty acids are catabolized in a process called beta-oxidation that takes place in the mitochondrial matrix and converts their fatty acid chains into two carbon units of acetyl groups. The acetyl groups are picked up by CoA to form acetyl CoA that enters the citric acid cycle.
79
How does glycerol enter glycolysis?
Glycerol can be phosphorylated to glycerol-3-phosphate, which may enter glycolysis.
80
How did the evolution of photosynthesis influence glycolysis?
An early form of photosynthesis developed that did not use water as a source of hydrogen ions, but rather other molecules, like hydrogen sulfide, and subsequently produced sulfur rather than oxygen. It is thought that glycolysis developed at this time and could take advantage of the simple sugars being produced, but these reactions were unable to fully extract the energy stored in the carbohydrates. A later form of photosynthesis used water as a source of electrons and hydrogen, and generated free oxygen.
81
When did glycolysis likely evolve?
The development of glycolysis probably predated the evolution of photosynthesis, as it was well-suited to extract energy from materials spontaneously accumulating in the "primeval soup".
82
What is a GLUT protein?
An integral membrane protein that transports glucose.
83
What is an example of a GLUT protein?
Different forms of the GLUT protein control passage of glucose into the cells of specific tissues. GLUT4, for example, is a glucose transporter that is stored in vesicles. A cascade of events that occurs upon insulin binding to a receptor in the plasma membrane causes GLUT4-containing vesicles to fuse with the plasma membrane so that glucose may be transported into the cell.
84
How is cellular respiration regulated?
Control of a cell's metabolism prevents metabolic reactions from reaching a state of equilibrium in order to provide balanced amounts of energy in the form of ATP and generating the correct amount of intermediates used in the metabolism of macromolecules. Some reversible reactions are catalyzed by two different enzymes, one for each direction, which allows greater control of the rate of reaction, preventing equilibrium. A form of feedback activation or inhibition is by binding to the allosteric site of several of the enzymes used in the glucose pathways, in order to increase or decrease enzyme activity. The most commonly used molecules for this are ATP, ADP, AMP, NAD+, and NADH.
85
What is hexokinase?
An enzyme that phosphorylates hexoses, forming hexose phosphate. This is the first enzyme used in glycolysis, which catalyzes the phosphorylation of glucose. The negative charge of the phosphate prevents glucose-6-phosphate from leaving the cell. When this enzyme is inhibited, glucose diffuses out of the cell, and does not become a substrate for the respiration pathways in that tissue.
86
What is phosphofructokinase?
A kinase enzyme that phosphorylates fructose-6-phosphate in glycolysis. If this enzyme is inhibited, glucose-6-phosphate will accumulate. It is the main enzyme controlled in glycolysis. High levels of ATP, citrate, or a lower, more acidic pH decrease the enzyme's activity. An increase in citrate concentration can occur because of a blockage in the citric acid cycle.
87
What is pyruvate kinase?
The enzyme involved in the last step of glycolysis, which catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP. After glycolysis, pyruvate can proceed to be catabolized or converted into the amino acid alanine. If no more energy is needed and alanine is in adequate supply, this enzyme is inhibited. Its activity increases when fructose-1,6-bisphosphate levels increase. The regulation of pyruvate kinase involves phosphorylation by a kinase (pyruvate kinase kinase), resulting in a less-active enzyme. Dephosphorylation by a phosphatase reactivates it. It is also regulated by ATP (a negative allosteric effect).
88
How is conversion of pyruvate to acetyl CoA regulated?
If more energy is needed in a cell, more pyruvate will be converted into acetyl CoA through the action of pyruvate dehydrogenase. If acetyl groups or NADH accumulate, the rate decreases. Pyruvate dehydrogenase is also regulated by phosphorylation. A kinase phosphorylates it to form an inactive enzyme, and a phosphatase reactivates it. The kinase and the phosphatase are also regulated.
89
Which enzymes catalyze the reactions that make the first two molecules of NADH and so control the citric acid cycle?
Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.
90
How is alpha-ketoglutarate dehydrogenase regulated?
It is negatively regulated by ATP, NADH, and succinyl CoA. A decrease in activity of this enzyme may result in the alpha-ketoglutarate being used by the cell for amino acid (glutamate) synthesis.
91
How is the electron transport chain inhibited?
The enzymes of the electron transport chain are unaffected by feedback inhibition, but the chain is slowed by the buildup of ATP (indicating lower levels of energy usage).
