PM-132 - Mitochondria Handout (AY24-25) PDF

PM132 – Mitochondria and Energy Dr Nick Jones [email protected] uk  Catabolic v anabolic metabolism Mass=1 Catabolic Metabolism Anabol...

PM132 – Mitochondria and Energy Dr Nick Jones [email protected] uk  Catabolic v anabolic metabolism Mass=1 Catabolic Metabolism Anabolic Metabolism “breaking down” Protein “building up” consumption > synthesis Lipids consumption < synthesis e.g. Fatty acid oxidation Nucleic acid e.g. Fatty acid synthesis and protein translation Homeostasis Catabolism = Anabolism  Cells obtain energy by the oxidation of organic molecules Cells ‘powered’ by the energy stored in chemical bonds Energy is extracted by a process of gradual oxidation, or controlled burning Process is called aerobic respiration  Biological energy Adenosine triphosphate - ATP  Energy production Two types: mitochondria and chloroplasts Chemiosmotic coupling signifies a link between ATP (chemi) and membrane transport process (osmotic) Chemiosmotic process Why mammalian cells respire? Bioenergetics Survival Biosynthesis Growth Signaling Cellular function  The mitochondrion If we didn’t have mitochondria, all energy would have to come from anaerobic  Mitochondria – key structures Outer membrane Intermembrane space Inner membrane Cristae Matrix Also contains DNA & can manufacture some proteins Mitochondria – key structures Mitochondria – key structures  The many functions of mitochondria Buffering redox potential in the cytosol Membrane growth The urea cycle The biosynthesis of haem groups ROS production Localised mitochondrial functions Location Function Outer membrane Phospholipid synthesis Fatty acid desaturation Fatty acid elongation Inner membrane Electron transport Oxidative phosphorylation Pyruvate transport Fatty acyl CoA import Metabolite transport Matrix Pyruvate oxidation Citric acid cycle β oxidation of fats DNA replication RNA synthesis Protein synthesis Energy converting metabolism in the mitochondria  Redox potential Electron transfers provide most of the energy for life CH3COOH ← → CH3COO- + H+ ← NADH → NAD+ + H+ + 2e-  The four stages of respiration STAGE 1A – Glycolysis  The four stages of respiration STAGE 1B  The four stages of respiration STAGE 2 – Citric acid cycle  Glucose Nucleotides 3-PG Serine Glycine PEP Pyruvate Lactate Ac-CoA OAA Citrate Fatty Acids Malate TCA Cycle α-KG Succinate Glutamate Glutamine  The four stages of respiration STAGE 3 - ETC  The four stages of respiration STAGE 4 – ATP Intermembr synthesis H+ H+ ane space H+ H+ H+ H+ Inner membrane ATP synthase Matrix ADP + phosphate ATP  Oxidative phosphorylation VIA GLYCOLYSIS - 1 Glucose molecule gives 2 Acetyl CoAs, 4 NADH & 2 ATP ONWARD FROM GLYCOLYSIS - Each Acetyl CoA gives 3 NADH, 1 FADH2, 1 ATP in TCA cycle BUT you have x2 Acetyl CoA: 6 NADH, 2 FADH2, 2 ATP per glucose C6H12O6 + 6O2 6CO2 + 6H2O In excess of 30 ATP molecule per glucose!  Alternate fuels Fatty acids Amino acids such as glutamine Alternate fuels  Glucose Glucose Extracellular Transporters Intracellular Glutami Glycolysis Glucose TCA ne Hexokinase Cycle Citrate Glucose-6- phosphate Citric Acid Glutama ADP Cycle te ATP Malate ATP Succina Pyruvate Acetyl CoA te FADH2 NADH CO2 Oxidative Phosphorylation ATP Synthase O2 Free fatty acids ATP H2O  Mitochondria disorders Mitochondrial DNA depletion syndrome (MDDS) - Drop in mitochondrial DNA - Lactic acidosis Pyruvate dehydrogenase deficiency - Lactic acidosis  Energy production is central to metabolism https://www.youtube.com/watch?v=q-fKQuZ8dco Summary