Learning Objectives

How to identify a monosaccharide

A simple sugar that cannot be hydrolyzed into smaller carbohydrate units.

Look for a molecule that has:

1. 3 to 7 carbon atoms

2. A carbonyl group (aldehyde or ketone)

3. Multiple hydroxyl groups

Draw/describe the structure of D-Glucose

What is the cyclization of glucose?

The former carbonyl carbon becomes a new chiral center, called the anomeric carbon

Creates an α configuration and a β configuration

α configuration vs a β configuration of glucose

The α Configuration has an OH on the opposite side of the ring as Carbon 6

The β Configuration has an OH on the same side of the ring as Carbon 6

What is an O-glycosidic bond?

A covalent bond formed between the anomeric carbon of one sugar and a hydroxyl group of another.

Naming glycosidic linkages

Name based on the anomeric configuration (α or β) and the carbons involved (e.g., α1→4).

Anomeric carbon

The carbon derived from the carbonyl group in the open-chain form; it determines the α or β configuration.

Reducing sugar

A sugar that has a free anomeric carbon capable of acting as a reducing agent.

Significance of many branch points

Provides multiple non-reducing ends, increasing the rate of polymer breakdown or synthesis.

Significance of coiled structure

Compact storage form that enhances glucose density and enzyme access.

Significance of intrachain hydrogen bonds

Stabilizes helical structure and minimizes solubility (important in structural polysaccharides like cellulose).

Structure of starch

Mixture of amylose (linear, α1→4) and amylopectin (branched, α1→6).

Structure of glycogen

Highly branched glucose polymer with α1→4 linkages and α1→6 branches.

Structure of cellulose

Linear β1→4-linked glucose polymer with strong H-bonding between chains.

Function of starch structure

Stores energy in plants; branching allows moderate mobilization.

Function of glycogen structure

Efficient glucose storage in animals; many branches allow rapid release.

Function of cellulose structure

Rigid plant cell wall component due to linear, H-bonded fibers.

ATP hydrolysis thermodynamics

Although bond breaking requires energy, the overall reaction is favorable because ADP and Pi are more stable than ATP.

Kinetics of ATP hydrolysis

ATP hydrolysis is thermodynamically favorable but proceeds slowly without enzymatic catalysis.

Effect of ATP, ADP, Pi concentrations

Physiological concentrations of these molecules influence ΔG and the direction of ATP hydrolysis/synthesis.

Electron carriers

NAD+/NADH, NADP+/NADPH, and FAD/FADH₂ function in redox reactions to transfer electrons in metabolism.

NAD+/NADH function

Primarily functions in catabolic reactions to accept electrons during substrate breakdown.

NADP+/NADPH function

Primarily functions in anabolic reactions to donate electrons for biosynthesis.

Input of glycolysis

1 glucose, 2 NAD+, 2 ADP, and 2 inorganic phosphate (Pi).

Output of glycolysis

2 pyruvate, 2 NADH, 2 ATP (net), and 2 H₂O.

Net glycolysis reaction

Glucose + 2 NAD⁺ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 ATP + 2 H₂O.

ATP-consuming steps in glycolysis

Step 1 (hexokinase) and step 3 (PFK-1).

ATP-producing steps in glycolysis

Step 7 (phosphoglycerate kinase) and step 10 (pyruvate kinase).

NADH-producing step in glycolysis

Step 6 (glyceraldehyde-3-phosphate dehydrogenase).

Phosphorylation steps in glycolysis

Steps 1, 3, 7, and 10 involve phosphate transfer.

Redox step in glycolysis

Step 6 involves oxidation-reduction and NAD⁺ → NADH.

C–C bond cleavage step in glycolysis

Step 4 (aldolase cleaves fructose 1,6-bisphosphate into two 3-carbon sugars).

Isomerization steps in glycolysis

Steps 2, 5, and 8 rearrange functional groups without changing molecular formula.

Dehydration step in glycolysis

Step 9 (enolase removes water from 2-phosphoglycerate to form PEP).

Thermodynamic factors of glycolysis

Depend on substrate/product concentrations, enzyme activity, and ΔG values of steps.

Step 1 of glycolysis

Hexokinase converts glucose to glucose-6-phosphate using ATP.

Step 3 of glycolysis

PFK-1 converts fructose-6-phosphate to fructose-1,6-bisphosphate using ATP.

Step 10 of glycolysis

Pyruvate kinase converts phosphoenolpyruvate (PEP) to pyruvate, producing ATP.

Hexokinase regulation

Inhibited by its product, glucose-6-phosphate, in a feedback mechanism.

PFK-1 regulation

Activated by AMP and fructose 2,6-bisphosphate; inhibited by ATP and citrate.

Pyruvate kinase regulation

Activated by fructose 1,6-bisphosphate; inhibited by ATP and alanine.

Hexokinase IV activity regulation

Regulated by glucose concentration; low glucose causes sequestration of the enzyme in the nucleus.

Liver glucose export

Glucose can leave liver cells before phosphorylation, allowing it to regulate blood glucose levels.

General catabolic reactions

Break down macromolecules (proteins, fats, carbs) into smaller units, producing ATP and reducing equivalents.

Fructose 1,6-bisphosphate

A glycolysis intermediate formed in step 3; key for committing glucose to glycolysis.

Fructose 2,6-bisphosphate

A potent allosteric activator of PFK-1 and inhibitor of FBPase-1; regulates glycolysis and gluconeogenesis.

Role of F1,6BP in catabolism

Direct intermediate of glycolysis; used to split glucose into two 3-carbon sugars.

Role of F2,6BP in catabolism

Not a metabolic intermediate, but a regulator that promotes glycolysis and inhibits gluconeogenesis.

Evolutionary advantage of fermentation

Allows ATP production without oxygen and regenerates NAD⁺ to sustain glycolysis under anaerobic conditions.

Trigger for fermentation

Occurs when NADH builds up and NAD⁺ becomes limiting due to reduced oxygen availability.

What cells respond to in anaerobic conditions

Cells sense high NADH/NAD⁺ ratios and low ATP, which triggers fermentation to regenerate NAD⁺.

Regulated step of PPP

Glucose-6-phosphate dehydrogenase (G6PD), the first step of the pentose phosphate pathway.

Regulation of G6PD

Controlled by NADP⁺ levels (activates) and NADPH levels (inhibits); ensures balance of redox cofactors.

Citric Acid Cycle (TCA Cycle)

A series of enzyme-catalyzed reactions that oxidize acetyl-CoA to CO₂ while producing NADH, FADH₂, and GTP.

Function of TCA cycle

Links the breakdown of fuels to energy production via reducing equivalents for oxidative phosphorylation.

TCA cycle intermediate names

Citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaloacetate.

TCA cycle enzyme names

Citrate synthase, aconitase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, malate dehydrogenase.

Net reaction of citric acid cycle

Acetyl-CoA + 3 NAD⁺ + FAD + GDP + Pi + 2 H₂O → 2 CO₂ + 3 NADH + FADH₂ + GTP + CoA-SH + 3 H⁺.

Entry into citric acid cycle

Pyruvate is converted to acetyl-CoA by pyruvate dehydrogenase complex (PDH).

Regulated steps of TCA cycle

Citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase complex.

Regulation of citrate synthase

Inhibited by ATP, NADH, succinyl-CoA, and citrate; activated by ADP.

Regulation of isocitrate dehydrogenase

Inhibited by ATP and NADH; activated by ADP and Ca²⁺ (in muscle).

Regulation of α-ketoglutarate dehydrogenase

Inhibited by ATP, NADH, and succinyl-CoA; activated by Ca²⁺.

Importance of TCA cycle being cyclic

Ensures regeneration of oxaloacetate and flexibility to integrate with amino acid and fatty acid metabolism.

Pathways feeding into TCA cycle

Pyruvate from glycolysis, acetyl-CoA from fatty acid oxidation, and intermediates from amino acid catabolism.

Importance of oxaloacetate

Regenerates at the end of the cycle to combine with new acetyl-CoA, maintaining the cycle's continuity.

Step 1 glycolysis enzyme name

Hexokinase

Step 3 glycolysis enzyme name

Phosphofructokinase-1 (PFK-1)

Step 10 glycolysis enzyme name

Pyruvate kinase

Step 1 glycolysis substrate and product

Glucose → Glucose-6-phosphate

Step 3 glycolysis substrate and product

Fructose-6-phosphate → Fructose-1,6-bisphosphate

Step 10 glycolysis substrate and product

Phosphoenolpyruvate (PEP) → Pyruvate

Step 1 glycolysis regulation

Inhibited by glucose-6-phosphate (feedback inhibition)

Step 3 glycolysis regulation

Activated by AMP and F2,6-bisphosphate; inhibited by ATP and citrate

Step 10 glycolysis regulation

Activated by fructose-1,6-bisphosphate; inhibited by ATP and alanine

Hexokinase IV vs I activity

Hexokinase IV (liver) has a higher Km and responds to higher glucose; hexokinase I (muscle) has a low Km and works even at low glucose.

Hexokinase IV sequestration

Low glucose leads to its sequestration in the nucleus, limiting glycolysis in the liver.

Glucose export from liver

At low glucose, unphosphorylated glucose can leave the liver cell to maintain blood glucose levels.

Fermentation pathway in humans

Pyruvate is reduced to lactate to regenerate NAD⁺.

Enzyme for lactate formation

Lactate dehydrogenase (LDH)

Fermentation pathway in yeast

Pyruvate is converted to ethanol via acetaldehyde intermediate.

Yeast fermentation enzymes

Pyruvate decarboxylase and alcohol dehydrogenase

Human vs yeast fermentation

Humans lack pyruvate decarboxylase and cannot produce ethanol from pyruvate.

Step controlling PPP entry

Glucose-6-phosphate dehydrogenase (G6PD)

Regulation of PPP step

Activated by NADP⁺; inhibited by NADPH