Sandbox Reserved 508
From Proteopedia
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Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | ||
| - | [[Image:BCSMART_11-12_Figure_1.JPG|left|375px|thumb|FIGURE 1: Movement of Protons (H+) Across Inner Mitochondrial Membrane | + | [[Image:BCSMART_11-12_Figure_1.JPG|left|375px|thumb|'''FIGURE 1: Movement of Protons (H+) Across Inner Mitochondrial Membrane'''<br> |
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1. The electron transport chain pumps protons (H+) into the inter membrane space. | 1. The electron transport chain pumps protons (H+) into the inter membrane space. | ||
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of ADP to ATP. | of ADP to ATP. | ||
]] | ]] | ||
| - | [[Image:BCSMART_11-12_Figure_2.JPG|right|375px|thumb|FIGURE 2: ROS Production | + | [[Image:BCSMART_11-12_Figure_2.JPG|right|375px|thumb|'''FIGURE 2: ROS Production''' |
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1. During reperfusion (return of blood flow), the electron transport chain sends more protons (H+) into the inter membrane space, producing a high concentration. | 1. During reperfusion (return of blood flow), the electron transport chain sends more protons (H+) into the inter membrane space, producing a high concentration. | ||
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that carry a negative charge (O2 | that carry a negative charge (O2 | ||
-)]] | -)]] | ||
| - | [[Image:BCSMART_11-12_Figure_3.JPG|left|375px|thumb|FIGURE 3: UCP2 Relieving the High Concentration Gradient | + | [[Image:BCSMART_11-12_Figure_3.JPG|left|375px|thumb|'''FIGURE 3: UCP2 Relieving the High Concentration Gradient''' |
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One way the mitochondria can alleviate the proton buildup in the inter membrane space is to transport the protons (H+) back into the matrix. One possible protein involved in this transportation is uncoupling protein 2 (UCP2). | One way the mitochondria can alleviate the proton buildup in the inter membrane space is to transport the protons (H+) back into the matrix. One possible protein involved in this transportation is uncoupling protein 2 (UCP2). | ||
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1.UCP2 brings protons (H+) into the matrix, relieving the high concentration gradient. | 1.UCP2 brings protons (H+) into the matrix, relieving the high concentration gradient. | ||
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2.The “back up” of electrons and radical production is reduced, minimizing damage to cardiomyocytes. | 2.The “back up” of electrons and radical production is reduced, minimizing damage to cardiomyocytes. | ||
]] | ]] | ||
Revision as of 22:13, 29 May 2012
Uncoupling Protein 2
Introduction
Ischemic Heart Disease, the underlying cause of myocardial infarctions (heart attacks), is the leading cause of death in the world. Annually 785,000 American alone experience their first heart attack and 470,000 have a second or third. Cardiomyocytes (contracting heart cells) need energy to function optimally. Mitochondria in the cardiomyocytes provide that energy in the form of ATP through the metabolic process of oxidative phosphorylation, specifically the electron transport chain coupled to the enzyme ATP synthase. However, these mitochondria are vulnerable to injury during recovery after heart attack when the cardiomyocytes again receive blood flow (reperfusion) due to the over-production of reactive oxygen species (ROS or oxygen radicals). An excess of oxygen radicals can be very damaging due to their high chemical reactivity, specifically their ability to break chemical bonds in DNA, RNA, and proteins within the mitochondria and in the cell cytoplasm.
Abstract
Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2.
1. The electron transport chain pumps protons (H+) into the inter membrane space.
2. Protons (H+) in the matrix bond with oxygen (O2) to form water (H2O) in a reduction reaction.
3. Protons (H+) from the inter membrane space are used by ATP synthase, to provide energy for the conversion of ADP to ATP.
1. During reperfusion (return of blood flow), the electron transport chain sends more protons (H+) into the inter membrane space, producing a high concentration.
2. A high concentration gradient of protons (H+) “backs up” the electrons, allowing them to leave the ETC.
3. The excess electrons in the matrix can bind to oxygen, generating reactive oxygen species (ROS) that carry a negative charge (O2 -)
One way the mitochondria can alleviate the proton buildup in the inter membrane space is to transport the protons (H+) back into the matrix. One possible protein involved in this transportation is uncoupling protein 2 (UCP2). 1.UCP2 brings protons (H+) into the matrix, relieving the high concentration gradient.
2.The “back up” of electrons and radical production is reduced, minimizing damage to cardiomyocytes.
