INTRODUCTION TO CARBOHYDRATES AND GLYCOLYSIS SAFIYA RANSOME, P3 (safiya.ransome@me.com) PHARMACY BIOMEDICAL PREVIEW PROGRAM 2014 What are carbohydrates? • A major class of macromolecules • Largely composed of carbon, hydrogen, and oxygen. • Generally, carbohydrates serve two major functions: • Energy Storage • Ex: Sucrose is catabolized to glucose which is converted to ATP via glycolysis. • Structure • Ex: Cellulose is the major structural component of plant stems. Carbohydrate Structure • Empirical Formula: Cm(H2O)n • Example: Ribose is C5H10O5 • (But there are exceptions— what’s deoxyribose?) • Carbohydrates can exist in either open chain form or cyclic form. Cyclic form is more common. Carbohydrate Classification • Monosaccharide • Monomeric carbohydrate unit. Also known as a simple sugar. • Disaccharide • Two monomeric sugars linked together form a disaccharide. • Polysaccharide • Multiple monomeric units linked together form a polysaccharide. Monosaccharides • Can be further classified by the number of carbons: • Ex: 3 carbons = triose, 6 carbons = hexose • The most biologically relevant monosaccharide, glucose, is a hexose. Disaccharides • Monomeric units are bonded by O-glycosidic linkages, O is for oxygen. • Glycosidic linkages are formed by dehydration reactions. • Example: Glucose + Glucose ➔ Maltose + H2O (byproduct) • Common disaccharides: • Glucose + Glucose = Maltose • Glucose + Fructose = Sucrose • Glucose + Galactose = Lactose Polysaccharides • Composed of multiple monomeric units. • Also bonded by glycosidic linkages. • Common polysaccharides: • Starch and glycogen - energy storing polysaccharides • Cellulose and chitin - structural polysaccharides Glycolysis: Introduction • Glycolysis is the catalytic process by which ATP (energy) is produced from glucose. • Is an anaerobic process. Oxygen does not need to be present for it to occur. • Net Reaction: •1 mol glucose ➔ 2 pyruvate + 2 NADH + 2 ATP • Also known as the Embden-Meyerhof Pathway Glycolysis Overview: • Can be divided into two stages: • Stage 1: Energy Consumption • 2 ATP consumed • Energy is used to convert glucose into two phosphorylated trioses. • Stage 2: Energy Production • 4 ATP produced • 2 NADH produced • 2 pyruvate produced Glycolysis Overview Glycolysis: Step 1 • Enzyme: Hexokinase • Phosphorylates glucose to produce glucose-6phosphate •One ATP molecule consumed • Irreversible Step - Glycolysis process is now committed to continue. Glycolysis: Step 2 • Enzyme: Phosphoglucose Isomerase • Rearranges glucose-6-phosphate to fructose-6phosphate Glycolysis: Step 3 • Enzyme: Phosphofructokinase (PFK) • Phosphorylates fructose-6-phosphate to produce fructose-1,6-bisphosphate •One ATP Molecule is consumed • Irreversible Step Glycolysis: Step 4 • Enzyme: Aldolase • Cleaves fructose-1,6bisphosphate to two triose sugars: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3phosphate (GAP) • GAP continues through glycolysis; DHAP is converted into GAP by triose phosphate isomerase. PAUSE! • We are now moving into stage 2 of glycolysis, the energy production stage. • Take note! The previous step produced 2 molecules of GAP; individually each molecule will progress through each of the remaining steps. • You can think of this as stage 2 occurring twice. Glycolysis: Step 5 • Enzyme: Glyceraldehyde 3-phosphate dehydrogenase • Converts glyceraldehyde-3-phosphate to 1,3bisphosphoglycerate. • This step does NOT require ATP; inorganic phosphate is used to produce the new phosphate. •One molecule of NADH is produced. Glycolysis: Step 6 • Enzyme: Phosphoglycerate kinase • 1,3-bisposphoglycerate is de-phosphorylated to produce 3-phosphoglycerate •One molecule of ATP is produced. • This is known as substrate-level phosphorylation. Glycolysis: Step 7 • Enzyme: Phosphoglycerate mutase • Rearranges 3-phosphoglycerate to 2phosphoglycerate Glycolysis: Step 8 • Enzyme: Enolase • Converts 2-phosphoglycerate to phosphoenolpyrovate Glycolysis: Step 9 • Enzyme: Pyruvate kinase • Phosphoenolpyruvate is de-phosphorylated to produce pyruvate • One molecule of ATP is produced. • Irreversible step. The Balance Sheet Consumed Produced Net - 2 mol ATP 4 mol ATP 2 mol ATP 2 NADH 2 NADH 2 pyruvate 2 pyruvate Learning Tips! • Pay attention the molecule names, they will help you understand the order of the steps. • Pay attention to enzyme names: • Enzymes that are kinases are responsible for phosphorylation steps— either ATP consuming or producing. • Ex: hexokinase • Ex: Pyruvate kinase • Also, enzymes sometimes have similar names to the molecule that they act on: • Ex: Phosphoglycerate mutase acts on 3-phosphoglycerate