CHO 1 metabolism

Carbohydrate Metabolism

• Study notes on the break down, use, and control of carbohydrates in the body

Learning Objectives

• Understand carbohydrate breakdown, use, and control
• Describe how carbohydrates break down
• Describe what happens to glucose in metabolic processes
• Summarize what happens to pyruvate.
• Discuss how carbohydrate metabolism is regulated.

Metabolism

• The sum of all physical and chemical reactions in living organisms that maintains homeostasis
• Anabolism involves the assembly of complex molecules.
• Catabolism involves the breakdown of complex molecules.
• Intermediary metabolism is all the reactions involved in the storage and generation of metabolic energy.

Dietary Carbohydrate Digestion

• Starch breaks down into maltose and dextrins through salivary amylase and H2O
• Starch breaks down into maltose and isomaltose through pancreatic amylase and H2O
• Maltose breaks down into 2 glucose through maltase and H2O
• Isomaltose breaks down into 2 glucose through isomaltase and H2O
• Lactose breaks down into glucose and galactose through lactase and H2O
• Sucrose breaks down into glucose and fructose through sucrase and H2O

Monosaccharide Absorption

• Simple diffusion follows the concentration gradient.
  • Fructose and pentoses are absorbed this way.
• Facilitated transport uses GLUT5 in the small intestine for glucose, galactose, and fructose.
• GLUT-1 and GLUT-3: erythrocytes and brain
• GLUT-4: muscle
• GLUT-2: liver and kidney
• Active transport uses sodium glucose Transporter I for glucose and galactose.

Fate of Absorbed Sugars

• Fructose and galactose go to the liver.
• Liver converts to glucose
• Glucose goes for uptake by the tissues.

Glucose: The Preferred Carbohydrate

• Carbohydrates are the preferred source of energy for the body
• Final products of carbohydrate digestion are monosaccharides
  • These are 80% glucose, fructose, and galactose
• Fructose and galactose are converted to glucose in the liver and released back into the blood.
• Glucose must be broken down into a usable form of energy (ATP).

Metabolic Pathways of Glucose

• Oxidation results in energy production.
• Synthesis of other molecules includes carbohydrates, such as fructose, galactose, and pentoses.
• Synthesis of glycerol 3-phosphate result in triacylglycerol and phospholipids.
• Synthesis of acetyl CoA result in cholesterol and fatty acids.
• Non-essential amino acids are also synthesized.
• Storage: Glycogen in the liver and triacylglycerol in adipose tissue.
• Excretion in urine occurs.

Oxidation of Glucose

• Utilizes major pathways for energy production like glycolysis
  • Glycolysis produces pyruvate under aerobic conditions.
  • Glycolysis produces lactate under anaerobic conditions.
• TCA/Krebs cycle occurs under aerobic conditions.
  • Pyruvate is converted to acetate for oxidation through the Krebs' cycle.
• Minor pathways for synthesis of other molecules includes the Hexose monophosphate pathway
  • Used for production of pentoses and NADPH
• Uronic acid pathway also produces uronic acid, ascorbic acid & pentoses, but no ATP is produced from glucose.

Oxidation of Glucose, Continued

• Glucose metabolism involves glycolysis which occurs in the cytoplasm
• Glucose metabolism involves the citric acid cycle (mitochondrion)
• Glucose metabolism involves an electron transport chain (mitochondrion)
• Chemical reaction: C6H12O6 + 6O2 6CO2 + 6H2O
  • Yields 36 ATP molecules

Glycolysis

• Oxidation of glucose to pyruvate in the presence of O2, or lactate in the absence of O2 in the cytosol.
• Phase I: Energy utilization phase
  • Glucose is cleaved into 2 glyceraldehyde 3 phosphate molecules
  • This phase consumes 2 ATP molecules.
• Phase II: Energy recovery phase
  • 2 glyceraldehyde 3-phosphate molecules converted to pyruvate under aerobic conditions
  • Generates 10 ATP molecules
  • Generates lactate under anaerobic conditions with 4 ATPs.
• All reactions are reversible except for GK, PFK, PK catalyzed reactions

10 Steps of Glucose Metabolism

• Step 1: Synthesis of Glucose-6-phosphate
• Step 2: Conversion of glucose-6-phosphate to fructose-6-phosphate
• Step 3: Phosphorylation of fructose-6-phosphate
• Step 4: Cleavage of fructose-1,6-bisphosphate
• Step 5: Interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate
• Step 6: Oxidation of glyceraldehyde-3-phosphate
• Step 7: Phosphoryl group transfer
• Step 8: Interconversion of 3-phosphoglycerate and 2-phosphoglycerate
• Step 9: Dehydration of 2-phosphoglycerate
• Step 10: Synthesis of pyruvate

Fate of Pyruvate

• It gets converted into Citric acid cycle
• Which utilizes the electron transport chain
• Pyruvate also facilitates Alcoholic fermentation an Homolactic fermentation

Importance of Intermediates

• Pyruvate: Acetate, oxaloacetate, and lactate
• DiHydroxyAcetonePhosphate (DHAP) glycerol 3-phosphate
  • DHAP is used in triacylglycerol and phospholipid synthesis
• Non-essential amino acids are produced Pyruvate alanine
  • 3-phosphoglycerate serine
• Regulation occurs through stimulating hormone insulin, AMP, F6P
• Regulation occurs through key enzymes: GK, PFK, PK
• Regulation is inhibited by glucagon, ATP, citrate

Insulin-Glucose Storage

• ATP supports immediate cellular needs.
• Glucose not needed for ATP is anabolized into glycogen, stored in the liver and muscles for future use.
• Glycogenesis (anabolism) is synthesis of glycogen from glucose, which is stimulated by insulin.
• Glycogenolysis (catabolism) is inhibited through insulin

Metabolic Importance: Glucose

• Cells rely on insulin for efficient absorption of glucose from the blood.
• Insulin enhances ATP production by stimulating mitochondrial oxidative phosphorylation in skeletal muscle.

Glucose Conversion to Fat

• Excess glucose is preferentially stored as glycogen
• When cells are saturated with glycogen, additional glucose is converted to fat in the liver and stored in adipose tissue.

Insulin: Glucose>>>Fat Storage

• Insulin promotes the conversion of excess glucose in the liver that cannot be stored as glycogen into fatty acids.
• Fatty acids are packaged as triglycerides in low-density lipoproteins transported by blood to the adipose tissue.
• Insulin activates lipoprotein lipase in the capillary walls of adipose tissue, which splits triglycerides into fatty acids.
• This enables the fatty acids to be absorbed into adipose cells where they are converted again into triglycerides and stored.

Gluconeogenesis Pathway

• Utilizes Glucose from non-carbohydrate carbon substrates
• Catalyzed by glycolytic enzymes:
  • Hexokinase or Glucokinase
  • Phosphofructokinase
  • Pyruvate kinase
• Separate reactions are required to reverses the above: Glucose 6-P glucose + Pi
  • Fructose bisphosphate fructose 6-P + P₁
• Conversion of PYR PEP with 2 rxns:
  • PYR + CO2 + ATP -> oxaloacetate + ADP + P₁
  • Oxaloacetate + GTP PEP + CO2 +GDP