Glycolysis and Carbohydrate Digestion Quiz

Glycolysis Overview

• Glycolysis is a cytoplasmic pathway converting glucose to two pyruvates
• Releases energy in two substrate-level phosphorylation and one oxidation reaction
• Aerobic glycolysis occurs in cells with mitochondria and oxygen
• Anaerobic glycolysis occurs in the absence of mitochondria or oxygen (e.g., erythrocytes, exercising muscle)

Carbohydrate Digestion

• Salivary amylase hydrolyzes starch polymers to dextrin
• Acid in the stomach destroys salivary amylase
• Intestinal enzymes (maltase, isomaltase, lactase, sucrase) further break down disaccharides to monosaccharides
• Monosaccharides are absorbed by sodium/glucose transporters in mucosal cells

Glucose Transport

• Four glucose transporters (GLUTs) exist with different affinities for glucose
• GLUT 1 & 3 have high affinity for basal glucose uptake in tissues like brain, nerves, and red blood cells
• GLUT 2 is a low-affinity transporter in hepatocytes, initially capturing excess glucose for storage
• GLUT 4 is in adipose tissue and muscle and responds to blood glucose concentration; insulin increases its membrane presence

Glycolysis (Step 1): Hexokinase/Glucokinase

• Trapping glucose in cells via phosphorylation using ATP
• Hexokinase: widely distributed in tissues. Inhibited by glucose-6-phosphate
• Glucokinase: only in hepatocytes and pancreatic β-islet cells. Induced by insulin

Glycolysis (Step 2): Phosphofructokinase (PFK-1 and PFK-2)

• Rate-limiting enzyme in glycolysis
• Fructose 6-phosphate phosphorylated to fructose 1,6-bisphosphate using ATP
• Activated by AMP
• Inhibited by ATP and citrate
• Insulin activates PFK-2, increasing fructose 2,6-bisphosphate (F2,6-BP), which activates PFK-1
• Glucagon inhibits PFK-2, decreasing F2,6-BP and inhibiting PFK-1

Glycolysis (Step 3): Glyceraldehyde 3-phosphate Dehydrogenase

• Catalyzes oxidation and addition of inorganic phosphate to its substrate
• Produces a high-energy intermediate 1,3-bisphosphoglycerate
• NADH is produced
• Aerobic: NADH reoxidized in the mitochondria
• Anaerobic: NADH reoxidized by reducing pyruvate to lactate

Glycolysis (Step 4): 3-Phosphoglycerate Kinase

• Transfers a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
• Substrate-level phosphorylation; does not need oxygen

Glycolysis (Step 5): Pyruvate Kinase

• Last enzyme in aerobic glycolysis
• Catalyzes substrate-level phosphorylation of ADP using phosphoenolpyruvate (PEP) to pyruvate.
• Activated by fructose 1,6-bisphosphate (feed-forward activation)

Glycolysis (Step 6): Lactate Dehydrogenase

• Only used in anaerobic glycolysis
• Reoxidizes NADH to NAD, preventing glycolysis from halting
• Lactate dehydrogenase reduces pyruvate to lactate

Pyruvate Kinase Deficiency

• Second most common genetic deficiency causing hemolytic anemia
• Characterized by chronic hemolysis, decreased HbA's oxygen affinity, absence of Heinz bodies
• Loss of ion balance and osmotic fragility leads to swelling and lysis

Galactose Metabolism

• Galactose is transported to the liver and phosphorylated
• Galactose-1-phosphate is converted to glucose-1-phosphate
• Important enzymes: galactokinase, and galactose 1-phosphate uridyltransferase

Galactosemia

• Autosomal recessive trait
• Defective gene encoding galactokinase or galactose 1-phosphate uridyltransferase
• Symptoms include cataracts, jaundice, and hyperbilirubinemia
• Can result in decreased glucose synthesis and hypoglycemia

Lactose Intolerance

• Deficiency of lactase (enzyme responsible for digesting lactose)
• Symptoms include bloating, diarrhea, and cramps after lactose ingestion
• Treated with dietary restriction of lactose or lactase pills

Fructose Metabolism

• Fructose is found in fruit, honey, and sucrose
• Phosphorylated to fructose-1-phosphate
• Cleaved into glyceraldehyde and DHAP
• Deficiency of fructokinase is generally benign
• Deficiency of fructose-1-phosphate aldolase (aldolase B) (Hereditary fructose intolerance) is severe

Pyruvate Dehydrogenase Complex

• Catalyzes the conversion of pyruvate to acetyl-CoA
• Essential for aerobic metabolism
• Cofactors and coenzymes: TPP, lipoic acid, CoA, FAD, NAD