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86 Cards in this Set
- Front
- Back
Adenosine 5' Triphosphate (ATP)
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Store of free energy within the cell. The bonds bewteen phosphates in ATP are high energy bonds because their hydrolysis is accompanied by a relative large decrease in free energy.
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Glycolysis
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Initial stage in the breakdown of glucose. can happen in the absence of oxygen and provide all energy for anaerobic organisms.
1. One ATP is used to phosphorylate glucose to glucose-6-phosphate 2. This is converted to fructose-6-phosphate 3. Another ATP is used to make fructose-1,6-biphosphate 2. Glucose is broken down into pyruvate with net gain of two molecules of ATP |
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Hexokinase
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Catalyzes the initial phosphorylation of glucose and conversion to glucose-6-phosphate.
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Phosphofructokinase
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Converts fructose-6-phosphate to fructose-1,6-biphosphate. This enzyme is the key control element. It is inhibited by ATP which results in excess glucose-6-phosphate that inhibits hexokinase.
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Cleavage of fructose-1,6-biphosphate
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Yields two molecules of the three-carbon sugar glyceraldehyde-3-phosphate
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Fate of glyceraldehyde-3-phosphate
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Oxidized to 1,3-biphosphoglycerate
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Fate of 1,3-biphosphoglycerate
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High energy phosphate group is used to drive synthesis of ATP from ADP and in the process changed to 3-phosphoglycerate
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Fate of 3-phosphoglycerate
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Converted to phosphoenolpyruvate another high energy intermediate.
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Fate of phosphoenolpyruvate
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Is converted to pyruvate in a process that converts another ADP to ATP
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Total ATP in Glycolysis
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4 ATP results from conversion of glucose into 2 three carbon pyruvates. Two of these are consumed in the reaction resulting in 2 net ATP.
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NAD+
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Coenzyme that acts as a oxidizing agent and accepts electrons from glyceraldehyde-3-phosphate.
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NADH in anaerobic conditions
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Is reoxidized to NAD+ by conversion of pyruvate to lactate
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NADH in aerobic conditions
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Serves as a source of energy by donating electrons to electron transport chain where they are used to reduce O2 to H2O coupled with generation of ATP.
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Coenzyme A
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Serves as a carrier of acyl groups in various metabolic reactions. Is found in the mitochondria where pyruvate is converted to CO2 and H2O.
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Acetyl CoA
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One carbon of pyruvate is released as CO2 and the other two are added to CoA to form this also reducing one molecule of NAD+ to NADH.
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Citric acid cycle (Krebs cycle)
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Central pathway in oxidative metabolism.
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Fate of acetyl CoA
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Combines with oxaloacetate (four carbons) to yield citrate (six carbons)
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Fate of Citrate
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Eight further reactions yields two CO2 and regeneration of oxaloacetate forming one GTP which is used to drive synthesis of one ATP.
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Products of Citric acid cycle
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Three molecules of NADH and one molecule of reduced flavin adenine dinucleotide. Total ATP from TCA is 2 molecules.
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Oxidative phosphorylation
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Electrons of NADH and FADH2 combine with O2 and release energy driving synthesis of ATP from ADP.
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Electron transport chain
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Process takes place gradually by passage of electrons through a series of carriers in the inner mitochondrial membrane of eukaryotic cells.
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ATP generated per NADH
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Approximately 2.5 ATP
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ATP generated per FADH2
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Approximately 1.5 ATP (enters at a lower energy level)
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Breakdown of nucleotides for energy
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Can be broken down to sugars which then entery glycolysis
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Break down of amino acids for energy
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Can be broken down in citric acid cycle
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Break down of lipids for energy
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More efficient storage. First broken down the glycerol and free fatty acids. each fatty acid is joined to coenzyme A yielding a fatty acyl-CoA at the cost of one ATP. Fatty acids are then degraded in stepwise oxidative process, two carbons at a time and releasing one NADH and one FADH2 per oxidation. Acetyl CoA enters citric acid cycle and finishes.
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Electron Transport Chain
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To be harvested in a usable form energy must be produced gradually by the passage of electrons through a series of carriers. Organized into four complexes with a fifth complex coupling energy yielding reactions to ATP synthesis.
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Coenzyme Q (ubiquinone)
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Small, lipid-soluble molecule that carries electrons from complex I to complex III.
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Cytochrome c
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A peripheral membrane protein bound to outer face of inner membrane which carries electrons to complex IV (cytochrome oxidase)
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Cytochrome oxidase
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Location of electrons transferred to O2
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Chemiosmotic coupling
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ATP is generated by the use of energy stored in the form of proton gradients across biological membranes, rather than by direct chemical transfer of high-energy groups
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Electrochemical gradient
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pH and electric potential drive protons back into the matrix from the cytosol
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ATP synthase (F1F0 ATPase)
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Uses the electrochemical gradient to convert ATP.
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Pyruvate Dehydrogenase Complex (PDH)
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Key regulatory enzyme that converts pyruvate to AcetylCoA releasing one NADH. It is irreversible under physiological conditions because of large negative energy.
Components: 8 trimers of lipoamide reductase-transacetylase 6 dimers of dihydrolipoyl dehydrogenase 12 dimers of pyruvate decarboxylase 1. Thiamin pyrophosphate (B1, thiamin) 2. Lipoic acid 3. Flavin Adenine Dinucleotide (FAD, B2, riboflavin) 4. Nicotinamide adenine dinucleotide (NAD, B3, niacin) |
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Key regulatory enzymes of the TCA cycle
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1. Citrate synthase
2. Isocitrate dehydrogenase 3. alpha-ketogluterate |
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Substrate level phosphorylation in TCA cycle
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1 GTP generated from succinyl CoA. The other from NAD and FAD in oxidative phosphorylation.
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Total Yield of TCA cycle
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3 NADH, 1 FADH, 1 GTP, 12.5 ATP/pyruvate or 10 ATP/AcetylCoA
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Pyruvate carboxylase
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Uses biotin, B7 to drive pyruvate conversion to oxaloacetate stimulated by Acetyl CoA to replace intermediates used in TCA.
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Citrate Synthase
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Converts oxaloacetate to citrate.
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Isocitrate dehydrogenase
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Converts isocitrate to alpha-ketoglutarate releasing NADH and CO2.
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Alpha-ketoglutarate dehydrogenase
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Converts alpha-ketoglutarate to succinyl CoA releasing an NADH and CO2.
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Regulation of TCA cycle
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1. Signal metabolites
a. AMP like signals activate b. ATP like signals inhibit 2. Regulatory phosphorylations a. PDH complex -P is active b. PDH complex +P is inactive 3. Cofactor cycling a. NAD and FAD must be available to move reaction forward so can be a regulating step |
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Complex I
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NADH dehydrogenase/NADH oxidase - mediates the transfer of electrons from NADH to the membrane-mobile cofactors, ubiquinone (coenzyme Q)
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Complex II
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Succinate dehydrogenase. Receives electrons from TCA cycle intermediate, succinate that are transferred to FADH2 and then to coenzyme Q and then continues down pathway
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Complex III
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Cytochrome b-c1 reductase. Reduces the membrane-mobile cytochrome c.
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Complex IV
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Cytochrome c oxidase. Reduced cytochrome c is oxidized by oxygen.
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Semiquinone intermediates
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Electron carriers such as CoQ and flavin mononucleotide FMN that can accept or donate one electron at a time can form these to scavenge free radicals.
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Superoxide anion radicals
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Oxygen radicals that escape the mitochondria before they are fully reduced to water
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Reactive oxygen species
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Can cause damage to DNA and proteins
1. Hydrogen peroxide 2. Hydroxyl radicals |
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Enzymes that detoxify ROS
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1. Superoxide dismutase
2. Glutathione peroxidoes |
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Nicotinamine Adenine Dinucleotide
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NAD+ (oxidized) and NADH (reduced) take electrons from pyruvate and transfer them to electron transport chain. Important component is Vitamin B3, niacin
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Pellagra
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Deficiency in niacin, vitamin B 3 needed for NAD action. Results in GI, skin, neurological symptoms.
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Thiamin pyrophosphate
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Involved in decarboxylating pyruvate. Needs Vitamin B1.
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Beriberi
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Deficiency in vitamin B 1 leading to GI symptoms and neurological symptoms.
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Lipoic acid
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A cofactor involved in acetyl group transfer to CoASH. Transfers electrons to riboflavin.
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Flavin Adenine Dinucleotide
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Accepts electrons from lipoic acid and transfers them to the electron transport chain. In PDH flavin remains bound to protein. Riboflavin is the vitamin precursor (B2) to FAD.
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Deficiency in Vitamin B2
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Fissures in the mouth, inflammation of the tongue, skin disease, severe irritation of the eyes.
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Regulated enzymes of the TCA cycle
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1. PDH complex
2. Isocitrate dehydrogenase 3. alpha-ketogluterate dehydrogenase |
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Superoxide dismutase
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Takes two superoxide anion radicals and converts them to oxygen and hydrogen peroxide
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Glutathione peroxidase
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Catalyzes the reduction of hydrogen peroxide using glutathione as an electron source.
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Glutathion
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A tripeptide gamma-glutamylcysteinylglycine. Reduced form is a disulfide.
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Glutathione reductase
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GSSG is recycled back to GSH using this enzyme completing detoxyfication cycle.
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Amytal and rotenone
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Block NADH dehydrogenase and prevent the transfer of electrons from NADH-linked substrates
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Antimycin A
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Blocks the terminal step, the transfer of electrons to oxygen (respiration).
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Cyanide, carbon monoxide, and azide
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Block the terminal step, the transfer of electrons to oxygen
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Oligomycin
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Blocks synthesis of ATP by F1F0 ATPase
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Atractyloside and bongkrektate
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Inhibit the exchange of ADP and ATP between cytosol and mitochondria
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Uncouplers of oxidative phosphorylation
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Collapse the proton gradient preventing synthesis of ATP but increase respiration and electron transport.
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Mitochondrial uncoupling protein
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A protein expressed in brown fat in mammals to respond to the cold. generates heat in tissues from uncoupling the proton gradient.
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Dinitrophenol
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Small organic molecule that is membrane permeant in its pronated state collapsing the proton gradient.
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Mitochondrial myopathy
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Muscle weakness or neurological symptoms due to impaired mitochondrial function
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Mitochondrial myopathy, encephalophaty, lactic acidosis, and stroke-like episodes
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Materally inherited defects in genes encoding mitochondrial tRNAs
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Myoclonic epilepsy and ragged red fibers
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Maternally inherited defects in genes encoding mitochondrial tRNAs
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Glycogen
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Main storage source of energy in the muscle. Glycogen in muscle is used exclusively in muscle.
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The Glycolytic Pathway
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1. Once glucose is in the cell it is phosphorylated and trapped in muscle
2. After cleavage into 2 three-carbon molecules that can be interconverted by triose phosphate isomerase generates NADH. |
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Pyruvate kinase
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Formation of a CH bond after donation of phosphate of PEP to ADP drives the reaction to become favorable enabling ATP formation.
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Anaerobic glycolysis
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1. Used when oxygen is limiting as in vigrorous exercise
2. Needs to recycle NADH to prevent the end of glycolysis 3. lactate dehydrogenase recycles NADH back to NAD+ to allow continued flux through glycolysis |
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Cori Cycle
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Liver can recycle lactate produced by muscle back to glucose. Energy requiring pathway of gluconeogenesis.
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Glycogen synthase
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Makes glycogen in response to high energy signals.
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Glycogen phosphorylase
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Makes Glucose 1-P in response to low energy signals.
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Activation of glycogen degradation
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1. Activation of cAMP dependent protein kinase A phosphorylates phosphorylase kinase and activates it.
2. High calcium provides independent way to activate phosphorylase kinase leading to rapid activation during muscle contraction 3. Phosphorylase phosphatase is inactivated by phosphorylation leading to a large increase in degradation of glycogen |
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Control of phosphofructokinase 1
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1. A major control point for glycolysis, phosphofructokinase 1 and fructose-1,6-biphosphatase are reciprically regulated
2. PFK1 activation with inhibition of FBPase increases flux through glycolysis considerably. |
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Fructose-2,6-biphosphate
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1. P26P is made from F6P and provides signal that indicates availability of glucose for metabolism acting like AMP like signal.
2. In skeletal muscle, increased fructose 6 phosphate stimulates PFK2 activity and generates more F26P which stimulates PFK1 and activates glycolysis |
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Phosphocreatine as energy source in contracting muscle
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Muscle stores high energy phosphates in phosphocreatine. This molecule buffers the ATP concentration against change.
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Respiration
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The flow of electrons down the electron transport chain to oxygen
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How many protons are used to make one molecule of ATP
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3 protons
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