* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Metabolism of Carbohydrates
Photosynthetic reaction centre wikipedia , lookup
Photosynthesis wikipedia , lookup
Electron transport chain wikipedia , lookup
Light-dependent reactions wikipedia , lookup
Biosynthesis wikipedia , lookup
Butyric acid wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Lactate dehydrogenase wikipedia , lookup
Microbial metabolism wikipedia , lookup
Fatty acid synthesis wikipedia , lookup
Basal metabolic rate wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Adenosine triphosphate wikipedia , lookup
Phosphorylation wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Blood sugar level wikipedia , lookup
Glyceroneogenesis wikipedia , lookup
Citric acid cycle wikipedia , lookup
Carbohydrate Metabolism An Overview of Metabolism Adenosine Tri-Phosphate (ATP) Link between energy releasing and energy requiring mechanisms “rechargeable battery” ADP + P + Energy ATP Mechanisms of ATP Formation Substrate-level phosphorylation Substrate transfers a phosphate group directly Requires enzymes Phosphocreatine + ADP Creatine + ATP Oxidative phosphorylation Method by which most ATP formed Small carbon chains transfer hydrogens to transporter (NAD or FADH) which enters the electron transport chain Metabolism Metabolism is all the chemical reactions that occur in an organism Cellular metabolism Cells break down excess carbohydrates first, then lipids, finally amino acids if energy needs are not met by carbohydrates and fat Nutrients not used for energy are used to build up structure, are stored, or they are excreted 40% of the energy released in catabolism is captured in ATP, the rest is released as heat Anabolism Performance of structural maintenance and repairs Support of growth Production of secretions Building of nutrient reserves Catabolism Breakdown of nutrients to provide energy (in the form of ATP) for body processes Nutrients directly absorbed Stored nutrients Cells and Mitochondria Cells provide small organic molecules to mitochondria Mitochondria produce ATP used to perform cellular functions Metabolism of Carbohydrates Carbohydrate Metabolism Primarily Fructose and galactose enter the pathways at various points All glucose cells can utilize glucose for energy production Glucose uptake from blood to cells usually mediated by insulin and transporters Liver is central site for carbohydrate metabolism Glucose uptake independent of insulin The only exporter of glucose Blood Glucose Homeostasis Several cell types prefer glucose as energy source (ex., CNS) 80-100 mg/dl is normal range of blood glucose in non-ruminant animals 45-65 mg/dl is normal range of blood glucose in ruminant animals Uses of glucose: Energy source for cells Muscle glycogen Fat synthesis if in excess of needs Fates of Glucose Fed state Storage as glycogen Liver Skeletal muscle Storage as lipids Adipose tissue Fasted state Metabolized for energy New glucose synthesized Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change High Blood Glucose Pancreas Insulin Muscle Glucose absorbed Glycogen Glucose absorbed Adipose Cells Glucose absorbed immediately after eating a meal… Glucose Metabolism Four major metabolic pathways: Immediate source of energy Pentophosphate pathway Glycogen synthesis in liver/muscle Precursor for triacylglycerol synthesis Energy status (ATP) of body regulates which pathway gets energy Same in ruminants and non-ruminants Fate of Absorbed Glucose 1st Priority: glycogen storage Stored in muscle and liver nd 2 Priority: provide energy Oxidized to ATP 3rd Priority: stored as fat Only excess glucose Stored as triglycerides in adipose Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Ribose-5-phosphate Glycolysis Pyruvate Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Ribose-5-phosphate Glycolysis Pyruvate Glycolysis Sequence of reactions that converts glucose into pyruvate Relatively small amount of energy produced Glycolysis reactions occur in cytoplasm Does not require oxygen Lactate (anaerobic) Glucose → 2 Pyruvate Acetyl-CoA (TCA cycle) Glycolysis Glucose + 2 ADP + 2 Pi 2 Pyruvate + 2 ATP + 2 H2O First Reaction of Glycolysis Traps glucose in cells (irreversible in muscle cells) Glycolysis - Summary Glucose (6C) 2 ATP 4 ADP 2 ADP 4 ATP 2 NAD 2 NADH + H 2 Pyruvate (3C) Pyruvate Metabolism Three fates of pyruvate: Conversion to lactate (anaerobic) Conversion to alanine (amino acid) Entry into the TCA cycle via pyruvate dehydrogenase pathway (create ATP) Pyruvate Metabolism Three fates of pyruvate: Conversion to lactate (anaerobic) Conversion to alanine (amino acid) Entry into the TCA cycle via pyruvate dehydrogenase pathway Anaerobic Metabolism of Pyruvate to Lactate Problem: + During glycolysis, NADH is formed from NAD + Without O2, NADH cannot be oxidized to NAD + No more NAD All converted to NADH Without NAD+, glycolysis stops… Anaerobic Metabolism of Pyruvate Solution: Turn NADH back to NAD+ by making lactate (lactic acid) (reduced) (oxidized) (oxidized) (reduced) Anaerobic Metabolism of Pyruvate ATP Two ATPs (net) are produced during the anaerobic breakdown of one glucose yield The 2 NADHs are used to reduce 2 pyruvate to 2 lactate Reaction is fast and doesn’t require oxygen Pyruvate Metabolism - Anaerobic Lactate Dehydrogenase Pyruvate Lactate NADH NAD+ Lactate can be transported by blood to liver and used in gluconeogenesis Cori Cycle Lactate is converted to pyruvate in the liver Pyruvate Metabolism Three fates of pyruvate: Conversion to lactate (anaerobic) Conversion to alanine (amino acid) Entry into the TCA cycle via pyruvate dehydrogenase pathway Pyruvate metabolism Convert Keto acid to alanine and export to blood Amino acid Pyruvate Metabolism Three fates of pyruvate: Conversion to lactate (anaerobic) Conversion to alanine (amino acid) Entry into the TCA cycle via pyruvate dehydrogenase pathway Pyruvate Dehydrogenase Complex (PDH) Prepares pyruvate to enter the TCA cycle Aerobic Conditions Electron Transport Chain TCA Cycle PDH - Summary Pyruvate 2 NAD 2 NADH + H CO2 Acetyl CoA TCA Cycle In aerobic conditions TCA cycle links pyruvate to oxidative phosphorylation Occurs in mitochondria Generates 90% of energy obtained from feed Includes metabolism of carbohydrate, protein, and fat Oxidize acetyl-CoA to CO2 and capture potential energy as NADH (or FADH2) and some ATP TCA Cycle - Summary Acetyl CoA 3 NAD 3 NADH + H 2 CO2 1 FAD 1 FADH2 1 ADP 1 ATP Oxidative Phosphorylation and the Electron Transport System Requires coenzymes (NAD and FADH) + as H carriers and consumes oxygen Key reactions take place in the electron transport system (ETS) Cytochromes of the ETS pass H2’s to oxygen, forming water Oxidation and Electron Transport Oxidation of nutrients releases stored energy Feed donates H+ + H ’s transferred to co-enzymes NAD+ + 2H+ + 2eFAD + 2H+ + 2e- NADH + H+ FADH2 So, What Goes to the ETS??? From each molecule of glucose entering glycolysis: 1. From glycolysis: 2 NADH 2. From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH 3. From TCA cycle (TCA) : 6 NADH and 2 FADH2 TOTAL: 10 NADH + 2 FADH2 Electron Transport Chain NADH + H+ and FADH2 enter ETC Travel through complexes I – IV + H flow through ETC and eventually attach to O2 forming water NADH + FADH2 + H 3 ATP 2 ATP Electron Transport Chain Total ATP from Glucose Anaerobic glycolysis – 2 ATP + 2 NADH Aerobic metabolism – glycolysis + TCA 31 ATP from 1 glucose molecule Volatile Fatty Acids Produced by bacteria in the fermentation of pyruvate Three major VFAs Acetate Propionate Energy source and for fatty acid synthesis Used to make glucose through gluconeogenesis Butyrate Energy source and for fatty acid synthesis Some use and metabolism (alterations) by rumen wall and liver before being available to other tissues Use of VFA for Energy Enter TCA cycle to be oxidized Acetic acid Propionic acid Yields 10 ATP Yields 18 ATP Butyric acid Yields 27 ATP Little butyrate enters blood Utilization of VFA in Metabolism Acetate Energy Carbon source for fatty acids Adipose Mammary gland Not used for net synthesis of glucose Propionate Energy Primary precursor for glucose synthesis Butyrate Energy Carbon source for fatty acids - mammary Effect of VFA on Endocrine System Propionate Increases blood glucose Stimulates release of insulin Butyrate Not used for synthesis of glucose Stimulates release of insulin Stimulates release of glucagon Increases blood glucose Acetate Not used for synthesis of glucose Does not stimulate release of insulin Glucose Stimulates release of insulin A BRIEF INTERLUDE… Need More Energy (More ATP)?? Working animals Increase carbon to oxidize Increased kidney size, glomerular filtration rate Increased ability to deliver oxygen to tissues and get rid of carbon dioxide Increased liver size and blood flow to liver Increased ability to excrete waste products Increased gut size relative to body size Increased feed intake Increased digestive enzyme production Increased ability to process nutrients Horses, dogs, dairy cattle, hummingbirds! Lung size and efficiency increases Heart size increases and cardiac output increases Increase capillary density Increased ability to oxidize small carbon chains Increased numbers of mitochondria in cells Locate mitochondria closer to cell walls (oxygen is lipid-soluble) Hummingbirds Lung oxygen diffusing ability 8.5 times greater than mammals of similar body size Heart is 2 times larger than predicted for body size Cardiac output is 5 times the body mass per minute Capillary density up to 6 times greater than expected Rate of ATP Production (Fastest to Slowest) Substrate-level phosphorylation Glucose Pyruvate Lactate Aerobic carbohydrate metabolism Creatine + ATP Anaerobic glycolysis Phosphocreatine + ADP Glucose Pyruvate CO2 and H2O Aerobic lipid metabolism Fatty Acid Acetate CO2 and H2O Potential Amount of Energy Produced (Capacity for ATP Production) Aerobic lipid metabolism CO2 and H2O Glucose Pyruvate CO2 and H2O Anaerobic glycolysis Acetate Aerobic carbohydrate metabolism Fatty Acid Glucose Pyruvate Lactate Substrate-level phosphorylation Phosphocreatine + ADP Creatine + ATP Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Ribose-5-phosphate Glycolysis Pyruvate Pentose Phosphate Pathway Secondary metabolism of glucose Produces NADPH Similar to NADH Required for fatty acid synthesis Generates essential pentoses Ribose Used for synthesis of nucleic acids Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Ribose-5-phosphate Glycolysis Pyruvate Energy Storage Energy from excess carbohydrates (glucose) stored as lipids in adipose tissue Acetyl-CoA (from TCA cycle) shunted to fatty acid synthesis in times of energy excess Determined by ATP:ADP ratios High ATP, acetyl-CoA goes to fatty acid synthesis Low ATP, acetyl CoA enters TCA cycle to generate MORE ATP Glucose Utilization Adipose Energy Stores Glycogen Glycogenesis Glucose Pentose Phosphate Pathway Ribose-5-phosphate Glycolysis Pyruvate Glycogenesis Liver 7–10% of wet weight Use glycogen to export glucose to the bloodstream when blood sugar is low Glycogen stores are depleted after approximately 24 hrs of fasting (in humans) De novo synthesis of glucose for glycogen Glycogenesis Skeletal muscle 1% of wet weight More muscle than liver, therefore more glycogen in muscle, overall Use glycogen (i.e., glucose) for energy only (no export of glucose to blood) Use already-made glucose for synthesis of glycogen Fates of Glucose Fed state Storage as glycogen Liver Skeletal muscle Storage as lipids Adipose tissue Fasted state Metabolized for energy New glucose synthesized Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change Fasting Situation in Non-Ruminants Where does required glucose come from? Breakdown or mobilization of glycogen stored by glucagon Glycogenolysis Glucagon - hormone secreted by pancreas during times of fasting Mobilization of fat stores stimulated by glucagon and epinephrine Lipolysis Triglyceride = glycerol + 3 free fatty acids Glycerol can be used as a glucose precursor The breakdown of muscle protein with release of amino acids Proteolysis Alanine can be used as a glucose precursor Low Blood Glucose Pancreas Muscle Insulin Proteins Broken Down Glycogen Glucose released Adipose Cells Glycerol, fatty acids released In a fasted state, substrates for glucose synthesis (gluconeogenesis) are released from “storage”… Gluconeogenesis Necessary process Glucose is an important fuel Central nervous system Red blood cells Not simply a reversal of glycolysis Insulin and glucagon are primary regulators Gluconeogenesis Vital for certain animals Ruminant species and other pre-gastric fermenters Convert carbohydrate to VFA in rumen Feline species Little glucose absorbed from small intestine VFA can not fuel CNS and RBC Diet consists primarily of fat and protein Little to no glucose absorbed Glucose conservation and gluconeogenesis are vital to survival Gluconeogenesis Synthesis of glucose from non-carbohydrate precursors during fasting in monogastrics Glycerol Amino acids Lactate Pyruvate Propionate Supply carbon skeleton There is no glucose synthesis from fatty acids Carbohydrate Comparison Primary energy substrate MOST monogastrics = glucose Ruminant/pre-gastric fermenters = VFA Primary substrate for fat synthesis MOST monogastrics = glucose Ruminant = acetate Extent of glucose absorption from gut MOST monogastrics = extensive Ruminant = little to none Carbohydrate Comparison Cellular demand for glucose Nonruminant = high Ruminant = high Importance of gluconeogenesis MOST monogastrics = less important Ruminant = very important