Cellular respiration is exergonic
Biology 1002B Lecture 7 Energy Transformation 2 -
Photosynthesis is endergonic and anabolic. Cellular respiration is exergonic and catabolic. Cellular respiration is converting free energy in CH bonds into ATP. Potential energy in food has lots of CH bonds, is conserve energy by changing to a form that cells can use (ATP).
Cellular Respiration (what we should know for exam): - Where is it found in cell? - What glycolysis does it do? - How does free energy change in relative amounts? - Does it require oxygen? - Where is the carbon? Starting with glucose we have 6 carbons. - Compare with photosynthesis (photosynthetic electron transport). Glycolysis: - Splitting of glucose, beginning of cellular respiration. - Almost every living organism has - Cytosolic pathway, don’t need specialized membrane, just need enzymes floating around in cytosol. - Nothing particularly eukaryotic about cellular respiration. - Only the location is different in eukaryotes as opposed to in bacteria for example. - Two molecules of pyruvate is the product of glycolysis, extract energy from glucose to reduce NAD to NADH (oxidation). - What has more free energy, a molecule of glucose or two molecules of pyruvate? A molecule of glucose. - Initial consumption of ATP (energy investment stage) and then get two ATP out and two NADH from one glucose molecule. - Energy coupling: first reaction, glucose and hexokinase come together with phosphate, gives positive delta G, endergonic. Couple this endergonic reaction with exergonic reaction. Exergonic reaction powers overall reaction. - Hydrolysis of ATP is the exergonic reaction in energy coupling. Water removes phosphate.
-
Energy coupling happens all over metabolic pathways. Kinetically it’s not a very fast reaction although it’s very spontaneous. Hexokinase can bind glucose or ATP; water cannot get into active site. Not really hydrolysis of ATP, more break down of ATP. Energy in terminal phosphate is conserved and transferred immediately to glucose. Want phosphorylate glucose because: makes the glucose more reactive, more readily wanting to break down, more free energy. Also, it stops it from leaving the cell (phosphate is negative, glucose is positive). Substrate-level phosphorylation: second reaction in glycolysis. Enzyme used is pyruvate kinase, catalyzes removal of phosphate from PEP, generates ATP. Phosphoryl transfer potential, when they can generate ATP through substrate level phospholrylation.
Mitochondria: Where rest of cellular respiration occurs
-
Chloroplasts have 3 membranes, mitochondria only have 2. Pyruvate in cytosol, if charged you have to transport it, won’t just leak through membrane. Mitochondrial matrix is where it wants to go. Lots of CH bonds in pyruvate. Decarboxylation occurs and it takes carbon dioxide from pyruvate. No free energy in this part of molecule so get rid of it. Dehydrogenase: group of enzymes which catalyze the oxidation and reduction of NAD NADP, etc. Gives 2 NADH, want to make acetyl group more reactive, coenzyme A helps with this. Acetyl CoA is the result of this reaction. Pyruvate dehydrogenase complex is where these enzymes for this part of cellular respiration are located. Citric Acid cycle pulls remaining electrons from CH bonds to get ATP, this occurs still in the matrix. 1 glucose gives two acetyl CoA, watch how many carbons in cycle. Oxaloacetate is substrate of citris acid cycles, 4 carbon compound. 2 carbon from actetyl CoA giving 6 carbon molecule citrate in first step of cycle. All carbon gets lost in this cycle. Remaining two carbon lost here. Free energy trapped in citrate. Then oxidizing citrate to reduce NAD, we get NADH, ADP and FADH2.
-
Oxidative phosphorylation (in matrix): goal is to get energy in electron carriers and convert to ATP. Electron carriers are the FADH, NADH and ADP generated in citric acid cycle. Complex 1 drives oxidation of NADH, mobile carrier UQ is very similar to PQ in photosynthetic electron transport. UQ brings electrons from complex 1 to complex 3. Oxidation of FADH2 occurs in complex 2. At the end oxygen combines with protons to give water. Lots of free energy in NADH2, energy is used to pump protons. Gradient established across membrane and can make ATP. Proton gradient. Protons flow through ATP synthase. ATP generated in the matrix. Oxidation part: oxidation of FADH2 and NADH Phosphorylation part: ATP synthase, very similar in photosynthetic electron transport. Two different processes: electron transport and phosphorylation.
Why do electrons move? -
Same as in photosynthesis NADH has very negative redox potential, molecule can readily become oxidized, strong reducing agent, doesn’t hold electrons very tightly. Oxygen is highly electronegative, wants electrons, and wants to be reduced, positive redox potential. Complex 1: proteins, they don’t become oxidized or reduced, its cofactors bounded to these proteins (like iron). Electron gets transferred from one of these cofactors all the way down to oxygen.
Uncoupling: -
-
Can uncouple oxidative phosphorylation. Electron generate proton gradient, protons move from matrix to intermembrane space, creates pH difference that builds up. Only way for protons to get back across is to go through ATP synthase. Protons catalyze synthesis of ATP. Uncoupler gives another route for protons to come back, not just through ATP synthase. Easier pathway to get back. Protons more likely to flow back through uncoupler than through ATP synthase. Electron transport not dependent on proton pumping, just doesn’t make any ATP if there is uncoupler. Uncoupler is very toxic. Allow any type of ion to leak. Chemical uncouplers. Uncoupling proteins. Regulates how coupled electron transport is to the synthesis of ATP through oxidative phosphorylation.
-
If you don’t couple proton gradient to ATP synthase, and you have an uncoupler there, protons just rush through, the potential energy in NADH is not conserved by making ATP, simply lost as heat. Present of uncoupler, not synthesizing anything, energy is lost to environment as heat. Play big role in newborns and hibernating bears, generates heat. In humans, may have a role in obesity. Lower expression of uncoupling proteins than someone who’s thin.
Oxygen supply controls the fate of pyruvate: -
Oxygen is terminal electron acceptor of respiration. Oxygen is at the end, terminal electron acceptor. What happens if you don’t have oxygen? Brain can’t do without oxygen. Need huge amounts of oxygen, need lots of ATP. In certain cells and tissues, if not enough oxygen, pyruvate never enters mitochondria and gets fermented either as ethanol or lactate in cytosol. What controls bifurcation (fork in the road): 1. Redox homeostasis, ration of oxidized to reduced NAD+/NADH. If ration is low (lots of NADH in relation to NAD+, no problem making NADH but problem oxidizing it) 2. Hypoxia-inducible factor: HIF-1, dimer (two proteins come together, alpha and beta to be functional) transcription factor, regulates and activates it. HIF-1 beta is in nucleus, HIF-1 alpha if a lot of oxygen around it gets degraded, synthesized in cytosol, tagged by ubequitin in proteasome. Under low oxygen it migrate to nucleus and binds to beta and produces functional HIF-1 transcription factor and activate transcription of lots of proteins under low oxygen. Low oxygen = hypoxia. HIF-1 activate a gene which encodes for pyruvate dehydrogenase kinase, this block pyruvate dehydrogenase complex, keeps pyruvate out of mitochondria.
Not enough oxygen? -
Lactate synthesis: fermentation, can’t oxidize NADH, glycolysis will stop. Conversion of pyruvate to lactate consumes NADH, regenerates NAD+ to keep glycolysis under low oxygen. Regulation of Cellular respiration:
Photosynthesis is endergonic and anabolic. Cellular respiration is exergonic and catabolic. Cellular respiration is converting free energy in CH bonds into ATP. Potential energy in food has lots of CH bonds, is conserve energy by changing to a form that cells can use (ATP).
Cellular Respiration (what we should know for exam): - Where is it found in cell? - What glycolysis does it do? - How does free energy change in relative amounts? - Does it require oxygen? - Where is the carbon? Starting with glucose we have 6 carbons. - Compare with photosynthesis (photosynthetic electron transport). Glycolysis: - Splitting of glucose, beginning of cellular respiration. - Almost every living organism has - Cytosolic pathway, don’t need specialized membrane, just need enzymes floating around in cytosol. - Nothing particularly eukaryotic about cellular respiration. - Only the location is different in eukaryotes as opposed to in bacteria for example. - Two molecules of pyruvate is the product of glycolysis, extract energy from glucose to reduce NAD to NADH (oxidation). - What has more free energy, a molecule of glucose or two molecules of pyruvate? A molecule of glucose. - Initial consumption of ATP (energy investment stage) and then get two ATP out and two NADH from one glucose molecule. - Energy coupling: first reaction, glucose and hexokinase come together with phosphate, gives positive delta G, endergonic. Couple this endergonic reaction with exergonic reaction. Exergonic reaction powers overall reaction. - Hydrolysis of ATP is the exergonic reaction in energy coupling. Water removes phosphate.
-
Energy coupling happens all over metabolic pathways. Kinetically it’s not a very fast reaction although it’s very spontaneous. Hexokinase can bind glucose or ATP; water cannot get into active site. Not really hydrolysis of ATP, more break down of ATP. Energy in terminal phosphate is conserved and transferred immediately to glucose. Want phosphorylate glucose because: makes the glucose more reactive, more readily wanting to break down, more free energy. Also, it stops it from leaving the cell (phosphate is negative, glucose is positive). Substrate-level phosphorylation: second reaction in glycolysis. Enzyme used is pyruvate kinase, catalyzes removal of phosphate from PEP, generates ATP. Phosphoryl transfer potential, when they can generate ATP through substrate level phospholrylation.
Mitochondria: Where rest of cellular respiration occurs
-
Chloroplasts have 3 membranes, mitochondria only have 2. Pyruvate in cytosol, if charged you have to transport it, won’t just leak through membrane. Mitochondrial matrix is where it wants to go. Lots of CH bonds in pyruvate. Decarboxylation occurs and it takes carbon dioxide from pyruvate. No free energy in this part of molecule so get rid of it. Dehydrogenase: group of enzymes which catalyze the oxidation and reduction of NAD NADP, etc. Gives 2 NADH, want to make acetyl group more reactive, coenzyme A helps with this. Acetyl CoA is the result of this reaction. Pyruvate dehydrogenase complex is where these enzymes for this part of cellular respiration are located. Citric Acid cycle pulls remaining electrons from CH bonds to get ATP, this occurs still in the matrix. 1 glucose gives two acetyl CoA, watch how many carbons in cycle. Oxaloacetate is substrate of citris acid cycles, 4 carbon compound. 2 carbon from actetyl CoA giving 6 carbon molecule citrate in first step of cycle. All carbon gets lost in this cycle. Remaining two carbon lost here. Free energy trapped in citrate. Then oxidizing citrate to reduce NAD, we get NADH, ADP and FADH2.
-
Oxidative phosphorylation (in matrix): goal is to get energy in electron carriers and convert to ATP. Electron carriers are the FADH, NADH and ADP generated in citric acid cycle. Complex 1 drives oxidation of NADH, mobile carrier UQ is very similar to PQ in photosynthetic electron transport. UQ brings electrons from complex 1 to complex 3. Oxidation of FADH2 occurs in complex 2. At the end oxygen combines with protons to give water. Lots of free energy in NADH2, energy is used to pump protons. Gradient established across membrane and can make ATP. Proton gradient. Protons flow through ATP synthase. ATP generated in the matrix. Oxidation part: oxidation of FADH2 and NADH Phosphorylation part: ATP synthase, very similar in photosynthetic electron transport. Two different processes: electron transport and phosphorylation.
Why do electrons move? -
Same as in photosynthesis NADH has very negative redox potential, molecule can readily become oxidized, strong reducing agent, doesn’t hold electrons very tightly. Oxygen is highly electronegative, wants electrons, and wants to be reduced, positive redox potential. Complex 1: proteins, they don’t become oxidized or reduced, its cofactors bounded to these proteins (like iron). Electron gets transferred from one of these cofactors all the way down to oxygen.
Uncoupling: -
-
Can uncouple oxidative phosphorylation. Electron generate proton gradient, protons move from matrix to intermembrane space, creates pH difference that builds up. Only way for protons to get back across is to go through ATP synthase. Protons catalyze synthesis of ATP. Uncoupler gives another route for protons to come back, not just through ATP synthase. Easier pathway to get back. Protons more likely to flow back through uncoupler than through ATP synthase. Electron transport not dependent on proton pumping, just doesn’t make any ATP if there is uncoupler. Uncoupler is very toxic. Allow any type of ion to leak. Chemical uncouplers. Uncoupling proteins. Regulates how coupled electron transport is to the synthesis of ATP through oxidative phosphorylation.
-
If you don’t couple proton gradient to ATP synthase, and you have an uncoupler there, protons just rush through, the potential energy in NADH is not conserved by making ATP, simply lost as heat. Present of uncoupler, not synthesizing anything, energy is lost to environment as heat. Play big role in newborns and hibernating bears, generates heat. In humans, may have a role in obesity. Lower expression of uncoupling proteins than someone who’s thin.
Oxygen supply controls the fate of pyruvate: -
Oxygen is terminal electron acceptor of respiration. Oxygen is at the end, terminal electron acceptor. What happens if you don’t have oxygen? Brain can’t do without oxygen. Need huge amounts of oxygen, need lots of ATP. In certain cells and tissues, if not enough oxygen, pyruvate never enters mitochondria and gets fermented either as ethanol or lactate in cytosol. What controls bifurcation (fork in the road): 1. Redox homeostasis, ration of oxidized to reduced NAD+/NADH. If ration is low (lots of NADH in relation to NAD+, no problem making NADH but problem oxidizing it) 2. Hypoxia-inducible factor: HIF-1, dimer (two proteins come together, alpha and beta to be functional) transcription factor, regulates and activates it. HIF-1 beta is in nucleus, HIF-1 alpha if a lot of oxygen around it gets degraded, synthesized in cytosol, tagged by ubequitin in proteasome. Under low oxygen it migrate to nucleus and binds to beta and produces functional HIF-1 transcription factor and activate transcription of lots of proteins under low oxygen. Low oxygen = hypoxia. HIF-1 activate a gene which encodes for pyruvate dehydrogenase kinase, this block pyruvate dehydrogenase complex, keeps pyruvate out of mitochondria.
Not enough oxygen? -
Lactate synthesis: fermentation, can’t oxidize NADH, glycolysis will stop. Conversion of pyruvate to lactate consumes NADH, regenerates NAD+ to keep glycolysis under low oxygen. Regulation of Cellular respiration:
