CARBOHYDRATE METABOLISM Dr. Madushani Silva (MBBS) North Colombo Teaching Hospital – Ragama

Metabolism Metabolism is all the chemical reactions that occur in an organism

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

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

Cells and Mitochondria Cells provide small organic molecules to mitochondria Mitochondria produce ATP used to perform cellular functions

Carbohydrate Metabolism Primarily glucose Fructose and galactose enter the pathways at various points All 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

Cellular Respiration

Cellular Respiration Is a series of reactions where fats, proteins, and carbohydrates, mostly glucose, are broken down to make CO2, water, and energy.

Cellular Respiration Cellular Respiration uses oxygen and glucose to produce Carbon dioxide, water, and ATP.

Cellular Respiration Glucose Oxygen gas Carbon dioxide Water Energy

How efficient is cell respiration? Energy released from glucose banked in ATP Energy released from glucose (as heat and light) Gasoline energy converted to movement 100% About 40% 25% Burning glucose in an experiment “Burning” glucose in cellular respiration Burning gasoline in an auto engine

Cellular Respiration The Stages of Cellular Respiration Cellular respiration has two stages. Glycolysis Aerobic and Anaerobic Respiration

Cellular Respiration Glycolysis The first stage of cellular respiration is called glycolysis. Aerobic and Anaerobic Respiration aerobic respiration (in the presence of oxygen) anaerobic respiration (in the absence of oxygen) 12

Glycolysis General Outline Glucose Pyruvic Acid No Oxygen Anaerobic Transition Reaction Fermentation Krebs Cycle ETS 36 ATP

General Outline of Aerobic Respiration Glycolysis Transition Reaction Krebs Cycle Electron Transport System

Overview of Aerobic Respiration

Cellular Respiration Stage One: Breakdown of Glucose Glycolysis Glucose is broken down to pyruvate during glycolysis, making some ATP. 13

Glycolysis Sequence of reactions that converts glucose into pyruvate

1 1 2 3 4 5 6 7 8 9 10

Energy Balance Sheet for the Oxydation of Glucose via Glycolysis Gains: 4 ATP 2 pyruvate 2 NADH + H+ Losses: 2ATP Glucose Phosphate NAD+ (recycled) Net Gain: + 2 ATP Mitochondria for further oxidation via the TCA/Krebs cycle

Cellular Respiration Stage Two: Production of ATP Krebs Cycle The Krebs cycle is a series of reactions that produce energy-storing molecules during aerobic respiration. Electron Transport Chain During aerobic respiration, large amounts of ATP are made in an electron transport chain. 14

The Fate of PYRUVATE Taken into mitochondria Broken down to ACETATE CO2 produced Binds to large protein Coenzyme A to produce acetyl Coenzyme A

The TCA or KREBS CYCLE CO2 NADH & FADH 2 more ATP

3rd alternative pathway… Electron Transport Chain Mitochondria and O2 needed Uses NADH and FADH produced in previous reactions To make more ATP

NADH FAHD

What is NADH?? FADH?? ENERGY CARRIER! Same for FADH Carrier to…?

Electron Transport System ETS (cytochrome chain) is a series of reduction/oxidation reactions Enzymes embedded in mitochondrial membranes

ETS makes how much ATP??

cytoplasm mitochondria

Fermentation in the Absence of Oxygen Fermentation When oxygen is not present, fermentation follows glycolysis, regenerating NAD+ needed for glycolysis to continue. Lactic Acid Fermentation In lactic acid fermentation, pyruvate is converted to lactate. 15

Fermentation

Glycogenolysis The process by which glucose is released from the liver

Fate of Glucose Synthesis and breakdown occur at all times 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

THE LIVER The liver is an important organ in blood glucose homeostasis

Blood glucose homeostasis -THE LIVER After feeding (stores some excess glucose as glycogen) In the fasted state (through glycogenolysis and gluconeogenesis, maintains blood glucose levels)

THE LIVER The hepatic uptake and output of glucose is controlled by: the concentration of key intermediates, and The activity of enzymes.

HORMONES Insulin Glucagon

Blood glucose homeostasis Insulin -Insulin is synthesized by the B (or β) cells in the pancreas. -Glucose stimulates insulin release

Blood glucose homeostasis Insulin -Insulin is an anabolic hormone which stimulates: - glucose uptake by muscle and adipose tissue, and increases: protein synthesis, glycogen synthesis lipogenesis.

Blood glucose homeostasis Glucagon -Glucagon is synthesized in the A (or α) cells of the pancreas. -Inhibited by glucose and insulin -Glucagon stimulates: glycogenolysis and gluconeogenesis (raising blood glucose concentrations).

PANCREASE

-Muscle has a higher rate of fuel utilization than other organs during exercise. -The brain, kidney and intestine utilize a higher percentage of available glucose at rest. -Alternative fuels are required during prolonged fasting or starvation

immediately after eating a meal… High Blood Glucose Glucose absorbed Insulin Pancreas Muscle Adipose Cells Glycogen immediately after eating a meal…

Fate of Absorbed Glucose 1st Priority: glycogen storage Stored in muscle and liver 2nd Priority: provide energy Oxidized to ATP 3rd Priority: stored as fat Only excess glucose Stored as triglycerides in adipose

Glucose Utilization Adipose Glycogen Glucose Ribose-5-phosphate Energy Stores Glycogen Glucose Pentose Phosphate Pathway Glycolysis Ribose-5-phosphate Pyruvate

Glucose Utilization Adipose Glycogen Glucose Ribose-5-phosphate Energy Stores Glycogen Glucose Pentose Phosphate Pathway Glycolysis Ribose-5-phosphate Pyruvate

The importance of regulating blood glucose levels !

Glucose: Obligate fuel for CNS & RBC’s CNS/Brain Dependent on glucose as primary source of fuel Uses ~120g glucose/day of total 160-200 g/d RBC Dependent on glucose Lack mitochondria

Anabolic in response to hyperglycemia Liver Stimulates glycogen synthesis, glycolysis, and fatty acid synthesis Muscle Stimulates glycogen synthesis

Anabolic in response to hyperglycemia Adipose Stimulates lipoprotein lipase resulting in uptake of fatty acids from chylomicrons and VLDL Stimulates glycolysis for glycerol phosphate synthesis (precurser to triglycerides)

Figure 9-1 Role in insulin in lowering blood glucose

Catabolic, in response to hypoglycemia Liver Activates glycogen degradation, gluconeogenesis Adipose Stimulates lipolysis and release of fatty acids

Figure 9-2 Role of glucagon in increasing blood glucose levels

Diabetes- What is it? Body is not producing or has lost sensitivity to insulin. Insulin is a hormone that is needed to convert sugar, starches and other food into energy. Insulin is produced in the body by the pancreas.

Vad happens to the carbohydrates from the food? Stored sugar in the liver (glycogen) Insulin from the pancreas - - - Fat/muscle cell Carbohydrates from food

A healthy cell Blood Urine test shows vessel 0 0 Cell Insulin O2 CO2 Water Energy Glucose Ketones 0 0

Starvation Blood Urine test shows vessel 0 + Cell (Insulin) in liver Fatty acids Ketones Glucose Ketones 0 +

Diabetes - lack of insulin Cell Blood vessel Urine test shows in liver Fatty acids Ketones Glucose Ketones +++ +++

Type I Usually diagnosed in children and young adults. Must take daily insulin shots to stay alive. Type I accounts for 5-10% of the population with diabetes.

Type II The most common form of the disease. Approximately 50% of men and 70% of women are obese at the time of diagnosis. Nearing epidemic proportions, due to increase # of older Americans, greater occurrence of obesity and sedentary lifestyles.

Types of Diabetes Secondary - a consequence from another disease. For example, pancreatitis or cystic fibrosis. Gestational Diabetes- diabetes during pregnancy. Impaired Glucose Tolerance- an intermediate between normal and diabetes.

Questions ?

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