L18 Fuels 2024.pdf

Fuels Dr. Hong Dao Nguyen School of Life and Environmental Sciences Learning objectives Distinguish between aerobic and anaerobic pathways Describe the oxidation of fatty acids and amino acids for ATP production Describe the processes involved in ATP production under an...

Fuels Dr. Hong Dao Nguyen School of Life and Environmental Sciences Learning objectives Distinguish between aerobic and anaerobic pathways Describe the oxidation of fatty acids and amino acids for ATP production Describe the processes involved in ATP production under anaerobic conditions Explain the importance of lactic acid fermentation in regenerating NADH for glycolysis Compare preferences for metabolic substrates between skeletal muscle, heart muscle and brain Compare differences in metabolic substrates utilised by tissues under fed, fasting and starvation conditions Cellular respiration: glucose catabolism when oxygen is available Glucose Glycolysis 2 ATP Pyruvate Intermediate reaction Acetyl CoA Krebs 2 ATP Cycle Electron Transport 32 ATP Chain Other sources of energy Amino acids Glucose Glycolysis 2 ATP Pyruvate Intermediate reaction Acetyl CoA Fatty acids Krebs 2 ATP Cycle Electron Transport 32 ATP Chain  Oxidation of fatty acids Fatty acid chains broken into 2 carbon acetic acid molecules Each acetic molecule combines with enzyme CoA to form acetyl CoA Basic structure Long hydrocarbon chain  Amino acids Glucose Glycolysis Pyruvate Intermediate reaction NH3 Ketone bodies Acetyl CoA Fatty acids Krebs Urea Cycle Electron Transport Chain  Amino acids Glucose Glycolysis Pyruvate Intermediate reaction NH3 Ketone bodies Acetyl CoA Fatty acids Krebs Urea Cycle Electron Transport Chain Oxidation of amino acids Excess amino acids produced from digesting proteins are transported to the liver Amino acid degradation produces sugars that can be converted to glucose or utilised in the Krebs Cycle Basic structure Carbohydrates Non-nitrogenous portion (acid group) - carbon, hydrogen., oxygen Nitrogenous portion H H O (amino group) Fats - mostly carbon and hydrogen H N C C OH Carboxyl group R Side chain Oxidation of amino acids Non-nitrogenous portion (acid group) Nitrogenous portion H H O (amino group) H N C C OH Carboxyl group NH3 R Side chain Urea Keto acid (ketone body) Amino group (NH2) and an extra H is removed to form ammonia (NH3) Non-nitrogenous portion (acid group) becomes a keto acid (ketone body) When oxygen is available Amino acids Glucose Lactic acid Glycolysis fermentation Pyruvate Lactate Intermediate reaction NH3 Ketone bodies Acetyl CoA Fatty acids in liver Krebs Urea Cycle Electron Transport Chain When oxygen is limiting Amino acids Glucose Lactic acid Glycolysis fermentation Pyruvate Lactate (O2 available) Intermediate reaction NH3 Ketone bodies Acetyl CoA Fatty acids Krebs Urea Cycle Oxidative phosphorylation In lactic acid fermentation, pyruvate is converted to lactate. Both pyruvate and lactate are 3 carbon molecules. However lactate has more hydrogen compared to pyruvate. This indicates that in lactic acid fermentation: A. Pyruvate is oxidised to lactate B. Pyruvate is reduced to lactate  Lactic acid fermentation Lactate production increases when: – the demand for ATP exceeds supply and oxygen is limiting – e.g strenuous exercise, inadequate blood supply due to blockage of the blood vessels Pyruvate is reduced to form lactate NADH is oxidised to NAD+ 2x Lactate Cytoplasm Lactic acid fermentation 2NAD+ 2x NADH 2NAD+ ADP ADP Net 2 ATP 2x NADH Net 2 ATP 2x Pyruvate Glucose Glycolysis Mitochondria image from Wikimedia Commons Concepts Our bodies exist in a dynamic catabolic-anabolic state Some nutrients are used to build bits and pieces of you You use 80-90% of the nutrients to provide energy Fed state - Nutrients absorbed from meals will supply energy for ~ 4 hours. - Nutrients are stored as glycogen and fat to give energy until the next meal Fasting state - Cells rely on energy that has been stored Nutrient preferences of tissues Tissue Preferred metabolic substrate(s) Brain Glucose, (ketone bodies) Skeletal muscle Fatty acids, glucose, ketone bodies Heart muscle Fatty acids, lactate, ketone bodies Red blood cells Glucose Many cancers Glucose (Warburg effect) When you are starving, your cells can use Ketone bodies Glucose made by the liver from amino acids and lactate When the brain lacks glucose… This is what happens in diabetic hypoglycemia Nutrient preferences of tissues Tissue Preferred metabolic substrate(s) Brain Glucose, (ketone bodies) Skeletal muscle Fatty acids, glucose, ketone bodies Heart muscle Fatty acids, lactate, ketone bodies Red blood cells Glucose Many cancers Glucose (Warburg effect) When you are starving, your cells can use Ketone bodies Glucose made by the liver from amino acids and lactate Imaging using cellular glucose uptake 18F-2-deoxy-glucose (FDG) Hofman and Hicks Cancer Imaging 2016 Not all parts of your body use energy at the same rate Normal 30 year old 66 kg woman – ~ 6,000 kJ per day Organ Energy use (kJ/day) Energy use (kJ/kg wet weight/day) Brain 1,275 1,004 Skeletal muscle 1,164 54 Liver 1,063 837 Heart 479 1,841 Kidneys 460 1,841 Adipose tissue 393 19 Wang et al. (2002) Obesity 20: 95-100 Skeletal muscle can increase energy usage enormously Woodchoppers need 18,000 kJ a day How much ATP from nutrients? There is more energy available per gram of fatty acid than per gram of glucose (106 ATP vs 34 ATP) Aerobic metabolism of glucose produces much more energy than anaerobic metabolism (34 ATP vs 2 ATP) Fatty acids are not used to produce ATP in the absence of O2  What ATP is used for ATP is the energy source for >95% of cellular activity – Contractility & motility (actin and myosin in muscles) – Ion pumping – Signaling – Biosynthesis… Heart – uses 0.135 µmol ATP per second = 8 x 1016 molecules per second , ~ 6 kg per day. – contains 1.35 mmol ATP (~ 0.7 g ATP) – Runs out of ATP within 10 seconds if ATP production is inhibited Starving What happens? Energy stores in a 70 kg person Glucose/Glycogen Triglycerides Mobilizable proteins Blood 250 kJ 200 kJ 0 kJ Liver 1,700 kJ 2,000 kJ 1,700 kJ Brain 30 kJ 0 kJ 0 kJ Muscle 5,000 kJ 2,000 kJ 100,000 kJ Adipose tissue 330 kJ 560,000 kJ 170 kJ Berg et al. (2002) From fed to fasting to starving Fed state: first 4 hours after a meal – Tissues use glucose from the meal – Excess glucose is stored as glycogen Fasting state: from 4 to 30 hours – Tissues other than brain reduce glucose usage – Brain uses glucose produced from glycogen and amino acids in the liver Starving: after 30 hours – Brain starts using ketone bodies rather than glucose – Other tissues stop using glucose – Liver makes ketone bodies from fatty acids (which were oxidised to acetyl CoA) – Liver and kidney make glucose from amino acids Ketoacidosis High serum and urine concentrations of ketone bodies Diabetic ketoacidosis (DKA) - Life-threatening complication of uncontrolled diabetes Starvation ketoacidosis - Occurs when body has been deprived of glucose and relies on fatty acids