deck_3745136 Flashcards

1
Q

outline the structure of mitochondria

A

1) cylinders around 0.5 – 1 um in diameter and up to 7 um long, can change shape and move around the cell.2) They can even fuse with one another and then move apart again.3)The number of mitochondria per cell varies according to the energy requirements of the cell. (Average 200)4) Liver cell: 1000-2000 mitochondria (20% of the total cell volume). Skeletal muscle: 4000 (in athletes). Some cells (e.g. fat cells, skin cells) only have a few mitochondria6) Two highly specialised membranes (inner and outer) that creates an intermembrane space and the internal matrix.7) The inner membrane is a highly specialised lipid bilayer that is particularly impermeable to ions and is the site of the electron transport chain and ATP synthesis.8)The inner membrane is also highly convoluted, forming folds called cristae that project into the matrix and serve to greatly increase the surface area of the inner membrane.9) The matrix contains enzymes that metabolise pyruvate and fatty acids to produce acetyl CoA and also enzymes that oxidise acetyl CoA in the citric acid cycle

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2
Q

outline the difference between oxidation and reduction

A

1) Reduction is the addition of an electron e-2) Oxidation is the removal of an electron e–NAD+ + 2 e- + 2H+ –> NADH + H+

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3
Q

outline what happens in glycolysis

A

1) This first series of metabolic reactions occurs in the cytoplasm not the mitochondrionGlucose undergoes phosphorylation, taking up a phosphate group from a molecule of ATP (reducing it to 2) ADP) and becoming glucose phosphate. This is then rearranged into another molecule – fructose phosphate, which is again phosphorylated to become fructose biphosphate. This six carbon sugar is then split into two smaller molecules which are each called triose phosphate (3-carbon)3) Finally, two molecules of ADP are phosphorylated for each triose phosphate to become ATP, and the sugar then has two hydrogen atoms removed using dehydrogenase enzymes to become a molecule known as pyruvate4) The hydrogen atoms are accepted by a coenzyme called NAD (nicotinamide adenine dinucleotide), reducing the coenzyme to reduced NAD (or NADH2). 5)Overall, as two ATP were used to phosphorylate the sugar and four were eventually made, it is said that the net ATP production per glucose molecule in glycolysis is 2 ATP. Two molecules of pyruvate and two molecules of reduced NAD were also produce. Under aerobic conditions net production can increase to 4 ATP molecules.

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4
Q

outline what happens in the citric acid cycle

A

1) The citric acid cycle occurs in the mitochondrial matrix and produces reduced electron carriers (e.g. NADH) for the electron transport chain.2) Electrons are transferred from NADH or FADH2 (produced by the citric acid cycle) to the electron transport chain3) Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O24) The chain’s function is to break the large free-energy drop from food to O2 into smaller steps that release energy in manageable amounts.5) Transfer of electrons from NADH to O2 occurs through three large respiratory enzyme complexes located in the inner mitochondrial membrane.

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5
Q

describe how the electron transport chain works

A

1) The electron transport chain is in the cristae of the mitochondrion2) Most of the chain’s components are proteins, which exist in multiprotein complexes3) The carriers alternate reduced and oxidized states as they accept and donate electrons4) Electrons drop in free energy as they go down the chain and are finally passed to O2, forming H2O

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6
Q

what is cytochrome oxidase?

A

1) The cytochrome oxidase complex accounts for around 90% of the total oxygen uptake in most cells.2) Cyanide is extremely toxic because it binds tightly to the cytochrome oxidase complex, stopping electron transport and greatly reducing ATP production.3) The cytochrome C protein also plays a crucial role in the regulation of cell death

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7
Q

All components of the respiratory chain carry electrons. Some carry H+ as well. outline the component that can carry electrons and those that can carry both electrons and H+

A

1)Carriers of electrons only:- FeS: iron sulphur proteins- Cytochromes2) Carriers of electrons + H+ (H carriers):- FMN : flavin mononucleotide- FAD :flavin adenine dinucleotide- Q: ubiquinone- Oxygen

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8
Q

what is ATP synthase

A

A multi-subunit protein with a mass of more than 500,000 Da that is responsible for producing ATP

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9
Q

describe chemiosmosis

A

1) Electron transfer in the electron transport chain causes proteins to pump H+ from the mitochondrial matrix to the intermembrane space2)H+ then moves back across the membrane, passing through channels in ATP synthase 3) ATP synthase uses the flow of H+ to drive phosphorylation of ADP to ATP4) This is an example of chemiosmosis, the use of energy in a H+ gradient to drive cellular work

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10
Q

outline the efficiency of energy capture

A

Glucose + O2 -> CO2 + H20 = + 686 Kcal/mol ADP + Pi -> ATP = - 7.3 Kcal/mol1) In respiration 1 glucose gives 38 ATP2) ATP from glucose = 38 x 7.3 kcal/mol (277 kcal/mol)Efficiency = 277/686 = 40% ( remainder lost as heat)

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11
Q

what is mitochondrial uncoupling?

A

1) Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They are found in all mammals and in plants. 2) Present in mitochondria of brown adipocytes (fat cells), the thermogenic cells that maintain body temperature.3) Uncoupling dissipates energy of substrate oxidation as heat.4) Uncoupling also allows continuous reoxidation of coenzymes that are essential to metabolic pathways.5) partial uncoupling of respiration prevents an exaggerated increase in ATP level that would inhibit respiration. 6) DNP makes membranes leaky to protons –and uncouples-Electron leakage can also occur to form oxygen free radicals (linked to ageing & cancer)- when the priority is to generate heat the the mitochondrial membrane is proton leaky and respiration ATP is uncoupled. -when the priority is energy conservation the respiration ATP is well coupled and the mitochondrial membrane is non proton leaky

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12
Q

describe how ATP is synthesised in mitochondria

A

Bacteria make ATP during respiration by pumping protons outwards and allowing the protons to re-enter the cell via an ATP synthase – just like mitochondria

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13
Q

define: chemiosmosis

A

Chemiosmosis is the movement of ions across a selectively permeable membrane, down their electrochemical gradient. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration or photosynthesis.

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14
Q

summarise chemiosmosis

A

1) Using aerobic oxidation the breakdown products of carbohydrates and fatty acids are converted by oxidation with oxygen to carbon dioxide and water, releasing energy in the form of high-energy electrons. 2) Cells break this reaction down into several small steps so that the energy released from one step closely matches the energy required for the next step. If all the energy was released in one step then much of it would be lost as heat which would be inefficient.3) The high energy electrons that are released are transferred along a series of electron carriers embedded in the membrane. The energy released by these transfers is used to pump protons (H+) across the membrane which in turn generates an electrochemical gradient.4) An ion gradient across a membrane is a form of stored energy (sometimes called the proton-motive force). H+ flows back down its electrochemical gradient through the ATP synthase enzyme which catalyzes the energy-requiring synthesis of ATP from ADP and inorganic phosphate (Pi).

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15
Q

name two ways cells can die

A

1)Necrosis: (uncontrolled cell death). Associated with disease.2)Apoptosis (programmed cell death or cell suicide). Apoptosis is an essential part of normal health and development. -In an average adult between 50 and 70 billion cells die through apoptosis per day. -In a year your entire body weight of cells will have died through apoptosis

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16
Q

outline the morphological of apoptosis in comparison to necrosis

A

necrosis:1) loss of membrane integrity 2) begins with swelling of cytoplasm and mitochondria 3) ends with total cell lysis 4) no vesicle formation, complete lysis 5) disintegration of organelles Apoptosis:1) membrane blebbing but no loss of integrity 2) aggregation of chromatin at the nuclear membrane 3) begins with shrinking of cytoplasm and condensation of nucleus 4) ends with fragmentation of cell into smaller bodies 5) formation of membrane bound vesicles 6) mitochondria become leaky due to pore formation involving proteins of the BCL-2 family

17
Q

outline the biological features of apoptosis and necrosis

A

necrosis:1) loss of regulation of ion homeostasis 2) no energy requirement - passive process 3) random disintegration on DNA4) postlytic DNA fragmentation apoptosis:1) tight regulated process involving activation and enzymatic steps 2) requires ATP3) non-random mono and oligonucleosomal length fragmentation of DNA 4) prelytic DNA fragmentation 5) release of various factors ( cytochrome C) into cytoplasm by mitochondria 6) activation of caspase cascade 7) alterations in membrane asymmetary

18
Q

outline the physiological significance of necrosis and apoptosis

A

necrosis: 1) affects groups of contiguous cells 2) evoked by non-physiological disturbances ( hypothermia , hypoxia, lytic viruses)3) phagocytosis by macrophages 4) significant inflammatory response apoptosis:1) affects individual cells 2) induced by physiological stimuli ( change in hormonal environment or lack of growth factors)3) phagocytosis by adjacent cells or macrophages 4) no inflammatory response

19
Q

outline the importance of apoptosis

A

1) Embryo development – sculpting tissue2) Immune system – destroying self-reacting immune cells.3) Immune system – destroying virus infected cells.4) Homeostasis – as a counter-balance to cell division and removal of old or damaged cells.5) Cancer – radiotherapy and most chemotherapy drugs work by inducing apoptosis. Many cancer cells have defects in the apoptosis pathways that make them resistant to apoptosis

20
Q

explain how apoptosis is triggered

A

1) Two main pathways for triggering apoptosis: - Receptor mediated (extrinsic pathway)- Mitochondria mediated (intrinsic pathway)2) The intrinsic pathway can be activated by a variety of cell stresses such as free radical damage, DNA damage, viral infection, or loss of survival signals.3) Both pathways induce apoptosis by activating a class of proteases in the cell called caspases.

21
Q

outline the role of caspases

A

1) Caspases - cysteine-aspartic proteases. A family of 12 proteases that exist as inactive pro-enzymes in cells. Following activation by cleavage they can activate other caspases in a cascade. they are the chief executioners of apoptosis2)There are two types of apoptotic caspases:initiator caspasesandeffector (executioner) caspases.3) Initiator caspases activate other caspases.4)Effector caspases break down cellular components such as the cytoskeleton and DNA.5) Activation of caspases is the point of no return in the process of apoptosis.

22
Q

what is the role of the plasma membrane in apoptosis?

A

Flip-over of phosphatidylserine ( component of the phospholipid membrane) from the inner lipid layer to the outer layer acts as an “eat me” signal to macrophages, which will destroy the apoptotic cell

23
Q

outline the role of mitochondria in apoptosis

A

1) Cytochrome C is located in the inner mitochondrial membrane and is an essential component of the electron transport chain.2) In the intrinsic apoptosis pathway, pores form in the outer mitochondrial membrane allowing release of cytochrome C into the cytosol. 3) Since cytochrome C is normally only found in the mitochondria, its release into the cytosol acts as a trigger for apoptosis. Cytochrome C binds to other cytosolic proteins to form a multi-protein complex called the apoptosome.

24
Q

what is an apoptosome ?

A

1) apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death stimulus.2) The formation of the apoptosome requires cytochrome C, a protein called Apaf-1, pro-caspase 9 and ATP.3) There are 7 molecules of each protein in the complete apoptosome with a combined molecular weight of 700 KDa.4) The end result is the cleavage and therefore activation of pro-caspase 9 into active caspase 9, an initiator caspase.

25
Q

What controls the release of cytochrome C from the mitochondria ?

A

1) The Bcl-2 family of proteins is responsible for the regulation of cytochrome C release from the mitochondria. 2) There are around 20 members of the family and consist of both pro-apoptotic and anti-apoptotic proteins. Their ability to induce apoptosis depends on the balance between the two types.3) Pro-apoptotic members of the Bcl-2 family are thought to work by inserting themselves into the mitochondrial surface and promoting the formation of large pores in the outer membrane that leads to the release of Cytochrome C.4)Anti-apoptotic members are thought to exist in the mitochondrial outer membrane and act to block the action of the pro-apoptotic members.5)Release of cytochrome C from the inner mitochondrial membrane to the cytosol, leads to the formation of the apoptosome and activation of the caspase cascade.6)The caspases are responsible for the destruction of the cell.