Carbohydrate Metabolism Notes
Digestion and Absorption of Carbohydrates
Digestion: Breakdown of food molecules via hydrolysis into simpler units for metabolic use.
Carbohydrate Digestion:
Begins in the mouth with salivary alpha-amylase.
Alpha-amylase hydrolyzes alpha-glycosidic linkages in starch and glycogen, yielding smaller polysaccharides and maltose.
Limited carbohydrate digestion in the mouth due to quick swallowing.
Stomach:
Minimal carbohydrate digestion.
Lacks carbohydrate digestion enzymes.
Salivary amylase is inactivated due to stomach acidity.
Small Intestine:
Primary site for carbohydrate digestion.
Pancreatic alpha-amylase breaks down polysaccharides into maltose (a disaccharide).
Intestinal Mucosal Cells:
Final digestion step occurs on outer membranes.
Disaccharidase enzymes convert disaccharides (maltose, sucrose, lactose) into monosaccharides (glucose, fructose, galactose).
Maltase: maltose to glucose.
Sucrase: sucrose to glucose and fructose.
Lactase: lactose to glucose and galactose.
Absorption:
Monosaccharides (glucose, galactose, fructose) absorbed into bloodstream via intestinal wall.
Intestinal villi contain blood capillaries facilitating active transport of monosaccharides.
ATP hydrolysis and protein carriers mediate monosaccharide passage through cell membranes.
Galactose and fructose are converted to products of glucose metabolism in the liver.
Glycolysis
Six-Carbon Stage (Steps 1-3): Energy-consuming phase where phosphate derivatives of glucose and fructose are formed via ATP coupling.
Step 1: Formation of Glucose-6-Phosphate
Glucose phosphorylation: ATP transfers a phosphate group to carbon 6 of glucose.
Catalyzed by hexokinase.
Endothermic reaction fueled by ATP hydrolysis.
Step 2: Formation of Fructose-6-phosphate
Glucose 6-phosphate isomerized to fructose-6-phosphate.
Enzyme: phosphoglucoisomerase.
Step 3: Formation of Fructose 1,6-bisphosphate
Further phosphorylation of fructose-6-phosphate.
Endothermic, powered by ATP hydrolysis.
Enzyme: phosphofructokinase.
Three-Carbon Stage (Steps 4-10): Intermediates are derivatives of glycerol and acetone, all phosphorylated derivatives of dihydroxyacetone, glyceraldehyde, glycerate, or pyruvate.
Step 4: Formation of Triose Phosphates
Six-carbon molecule splits into two three-carbon molecules: dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
Enzyme: aldolase.
Step 5: Isomerization of Triose Phosphates
Dihydroxyacetone phosphate is isomerized to glyceraldehyde 3-phosphate.
Enzyme: triosephosphate isomerase.
Step 7: Formation of 3-Phosphoglycerate
Diphosphate converted back to monophosphate; ATP-producing step.
High-energy phosphate group from 1,3-bisphosphoglycerate transferred to ADP, forming ATP.
Enzyme: phosphoglycerokinase.
Two ATP molecules produced per original glucose molecule.
Step 8: Formation of 2-phosphoglycerate
Isomerization of 3-phosphoglycerate to 2-phosphoglycerate.
Phosphate group moved from C-3 to C-2.
Enzyme: phosphoglyceromutase.
Step 9: Formation of Phosphoenolpyruvate
Alcohol dehydration reaction creating another high-energy phosphate compound.
Enzyme: enolase.
Step 10: Formation of Pyruvate
High-energy phosphate transferred from phosphoenolpyruvate to ADP, producing ATP and pyruvate.
Enzyme: pyruvate kinase.
Two ATP molecules produced per original glucose.
Steps 1, 3, and 10 are control points for glycolysis.
Net ATP Production: A net gain of two ATP molecules for every glucose molecule processed in glycolysis.
Overall Glycolysis Equation:
Entry of Galactose and Fructose: Both converted in the liver to intermediates that enter the glycolysis pathway.
Fructose: Phosphorylated by ATP to fructose 1-phosphate, then converted to glyceraldehyde (phosphorylated to enter glycolysis) and dihydroxyacetone phosphate.
Galactose: Phosphorylation by ATP yields glucose 1-phosphate, isomerized to glucose 6-phosphate.
Regulation of Glycolysis:
Control points: Steps 1, 3, and 10.
Step 1 (glucose to glucose 6-phosphate via hexokinase): Inhibited by glucose 6-phosphate (feedback inhibition).
Step 3 (fructose 6-phosphate to fructose 1,6-bisphosphate via phosphofructokinase): Inhibited by high ATP and citrate concentrations.
Step 10 (phosphoenolpyruvate to pyruvate via pyruvate kinase): Inhibited by high ATP concentrations. Pyruvate kinase and phosphofructokinase are allosteric enzymes.
Fates of Pyruvate
Oxidation to Acetyl CoA
Under aerobic conditions, pyruvate is oxidized to acetyl CoA by pyruvate dehydrogenase complex.
Acetyl CoA enters the mitochondrial matrix for processing in the citric acid cycle.
Most pyruvate from glycolysis is converted to Acetyl CoA.
Lactate Fermentation
Enzymatic anaerobic reduction of pyruvate to lactate, primarily in muscles.
Purpose: Converts NADH to NAD+ to increase the rate of glycolysis.
Lactate reconverted to pyruvate when aerobic conditions return.
Muscle fatigue from strenuous activity is due to lactate buildup.
Ethanol Fermentation
Enzymatic anaerobic conversion of pyruvate to ethanol and carbon dioxide.
Occurs in yeast and bacteria to regenerate NAD+.
Involves pyruvate decarboxylation (pyruvate decarboxylase) and acetaldehyde reduction to ethanol (alcohol dehydrogenase).
CO2 release during baking causes bread to rise.
Beer, wine, and alcoholic drinks are produced by ethanol fermentation of sugars.
Overall Reaction:
Regeneration of NAD+ from NADH: Critical for continuing glycolysis under anaerobic conditions via lactate or ethanol fermentation.
ATP Production for Complete Glucose Oxidation
NADH from glycolysis (step 6) cannot directly enter the electron transport chain because mitochondria are impermeable to NADH and NAD+.
Glycerol 3-phosphate-dihydroxyacetone phosphate transport system:
Shuttles electrons from NADH (not NADH itself) across the mitochondrial membrane.
Dihydroxyacetone phosphate and glycerol phosphate freely cross the membrane.
Interconversion shuttles electrons from NADH to FADH2.
ATP Totals:
Muscle and nerve cells: 30 ATP molecules.
26 from oxidative phosphorylation.
2 from glucose to pyruvate.
2 from GTP to ATP.
Heart and liver cells: 32 ATP molecules (using a more complex shuttle system).
Aerobic oxidation is more efficient than anaerobic processes by a factor of 15.
Glycogen Synthesis and Degradation
Glycogen: Branched polymer of glucose; storage form of carbohydrates in animals.
Muscle: Glucose source for glycolysis.
Liver: Maintains normal blood glucose levels.
Produced by glycogenesis.
Glycogenesis: Metabolic pathway for glycogen synthesis from glucose; involves three steps:
Formation of glucose 1-phosphate.
Formation of UDP glucose.
Glucose transfer to a glycogen chain.
Steps of Glycogenesis:
Step 1: Formation of glucose 1-phosphate from glucose 6-phosphate (from first step of glycolysis) via phosphoglucomutase.
Step 2: Formation of UDP glucose. UTP (uridine triphosphate) activates glucose 1-phosphate to UDP-glucose.
Step 3: Glucose transfer to glycogen chain. UDP-glucose glucose unit attached to the end of glycogen chain, producing UDP, which reacts with ATP to form UTP and ADP.
Adding one glucose unit to glycogen requires two ATP molecules (one for glucose 6-phosphate formation and one for UTP regeneration).
Glycogenolysis: Breakdown of glycogen to glucose-6-phosphate.
Not the reverse of glycogenesis; does not require UTP or UDP.
Two-step process: phosphorylation of a glucose residue and glucose 1-phosphate isomerization.
Steps of Glycogenolysis:
Step 1: Phosphorylation of a glucose residue. Glycogen phosphorylase removes an end glucose residue from glycogen as glucose 1-phosphate.
Step 2: Glucose 1-phosphate isomerization. Phosphoglucomutase isomerizes glucose 1-phosphate to glucose 6-phosphate (reverse of glycogenesis step one).
Glucose 6-phosphate enters glycolysis pathway.
Low glucose stimulates glycogenolysis in liver cells.
Glucose 6-phosphate is ionic and cannot cross the membrane.
Enzyme glucose 6-phosphatase (in liver, kidneys, intestine) converts glucose 6-phosphate to glucose.
Not present in muscle and brain tissues.
Free glucose transported to muscle and brain via blood.
Gluconeogenesis
Metabolic pathway for glucose synthesis from non-carbohydrate sources; not an exact reversal of glycolysis.
Glycogen stores depleted within 12-18 hours of fasting or less with heavy activity.
Maintains normal blood-glucose levels during inadequate carbohydrate intake.
90% of gluconeogenesis occurs in the liver.
Noncarbohydrate Starting Materials: Pyruvate, lactate (from muscles and red blood cells), glycerol (from triacylglycerol hydrolysis), certain amino acids (from dietary protein hydrolysis or muscle protein during starvation).
Overall Reaction:
Requires 4 ATP and 2 GTP, occurring at the expense of other ATP-producing processes.
Cori Cycle: Utilizes lactate as a pyruvate source.
Lactate from muscle cells enters the bloodstream and is transported to the liver.
Lactate dehydrogenase converts lactate to pyruvate in the liver.
Pyruvate is converted to glucose via gluconeogenesis.
Glucose enters bloodstream and is transported to muscles.
Terminology for Metabolic Pathways
Glycogenesis: Glycogen synthesis from glucose 6-phosphate (2 steps).
Gluconeogenesis: Pyruvate conversion to glucose (11 steps).
Glycolysis: Glucose conversion to pyruvate (10 steps).
Glycogenolysis: Glycogen conversion to glucose 6-phosphate.
"Lysis" = Breakdown, "Genesis" = Synthesis
Pentose Phosphate Pathway
Metabolic pathway using glucose to produce NADPH, ribose 5-phosphate (a pentose phosphate), and other sugar phosphates.
NADPH: Reduced form of NADP+ (nicotinamide adenine dinucleotide phosphate); phosphorylated version of NAD+/NADH; essential for biosynthetic pathways.
Two Stages:
Oxidative stage: Glucose 6-phosphate to ribulose 5-phosphate and CO2 (three steps).
Nonoxidative stage: Ribulose 5-phosphate (ketose) isomerized to ribose 5-phosphate (aldose).
Cellular Roles:
When ATP demand is high, end products enter glycolysis.
When NADPH demand is high, intermediates are recycled to glucose 6-phosphate for further NADPH production.
Generates ribose 5-phosphate for nucleic acid and coenzyme production.
Hormonal Control of Carbohydrate Metabolism
Second major control method (besides enzyme inhibition).
Three major hormones: Insulin, Glucagon, Epinephrine.
Insulin:
Produced by beta cells of the pancreas.
51 amino acid polypeptide.
Promotes glucose utilization by cells; lowers blood glucose levels; involved in lipid metabolism.
Release triggered by high blood-glucose levels.
Mechanism: Binds to protein receptors on cell surfaces, facilitating glucose entry and increasing glycogen synthesis rate.
Glucagon:
Produced in the pancreas by alpha cells.
29 amino acid peptide hormone.
Released when blood glucose levels are low.
Increases blood-glucose concentration by speeding up glycogenolysis in the liver.
Opposite effects of insulin.
Epinephrine:
Also called adrenaline.
Released by adrenal glands in response to anger, fear, or excitement.
Similar function to glucagon; stimulates glycogenolysis with a primary target of the muscle cells.
Promotes energy generation for quick action and functions in lipid metabolism.