Mutarotation of Glucose

How it happens - step by step

1. Cyclization creates an anomeric carbon. In solution, the open-chain aldehyde of glucose reacts with the C-5 hydroxyl group to form a 6-membered (pyranose) ring. C-1 becomes the anomeric carbon - a new chiral centre.
2. Two anomers are created. Depending on the orientation of the new -OH at C-1:
   • α-D-Glucopyranose - the C-1 -OH is axial (below the ring plane in Haworth; same side as the ring in Fischer projection). Specific rotation = +112°
   • β-D-Glucopyranose - the C-1 -OH is equatorial (above the ring plane; opposite side to CH₂OH). Specific rotation = +18.7°
3. The ring opens and re-closes. Either anomer can open back to the linear aldehyde form (< 0.1% of molecules at any time). When the ring re-closes, C-1 can adopt either orientation - so the anomers slowly interconvert.
4. Equilibrium is reached. The optical rotation drifts until it settles at a stable value of +52.5°, corresponding to a mixture of:
   • α form: ~36%
   • β form: ~63-64%
   • Open chain: < 0.1%
   The β anomer dominates because the equatorial -OH position is sterically more stable.

Diagrams

Key points to remember

• Mutarotation is spontaneous but slow at neutral pH in pure water; it is accelerated by acid, base, or the enzyme mutarotase (aldose-1-epimerase) found in cells.
• If the anomeric carbon forms a glycosidic bond (e.g., in starch, cellulose, glycoproteins), mutarotation is blocked - the bond is locked in α or β configuration. This is why glycogen (α-1,4 bonds) and cellulose (β-1,4 bonds) have completely different biological properties.
• Clinically relevant in glucose oxidase assays: the enzyme is specific for β-D-glucose, so some commercial preparations include mutarotase to ensure complete conversion of α to β form for accurate blood glucose measurement.

Invert Sugar

The Reaction

Sucrose  +  H₂O  →  D-Glucose  +  D-Fructose
(C₁₂H₂₂O₁₁)         (C₆H₁₂O₆)    (C₆H₁₂O₆)

• Invertase (β-fructofuranosidase, EC 3.2.1.26) - the enzyme in yeast, bees, and the intestinal brush border
• Sucrase (in intestinal mucosa) - same reaction
• Dilute acid (acid hydrolysis) - used industrially

Why is it called "Invert" Sugar?

Sucrose Structure - why hydrolysis releases both anomers

Biological and Clinical Relevance

• Digestion: Sucrase-isomaltase in the intestinal brush border hydrolyses dietary sucrose to invert sugar for absorption.
• Honey: Bees secrete invertase in their salivary glands; most of the sucrose in nectar is converted to invert sugar during honey making - this is why honey is primarily glucose + fructose.
• Food industry: Invert sugar syrup is sweeter than sucrose (fructose is ~1.7× sweeter than glucose), resists crystallisation, and retains moisture - making it valuable in confectionery, jams, and soft-centred chocolates.
• Sucrase deficiency: Congenital sucrase-isomaltase deficiency causes osmotic diarrhoea and bloating on sucrose ingestion in infants, due to unabsorbed sucrose drawing water into the gut.

Quick Summary

Sucrose (dextrorotatory, +66.5°) is hydrolysed by invertase into an equal mix of glucose and fructose. Because fructose is strongly levorotatory (-92°), the product mixture is levorotatory (-20°) - the rotation has been "inverted." This mixture is called invert sugar.

Cori Cycle (Lactic Acid Cycle)

The Two-Organ Cycle

• Glucose → 2 Pyruvate (glycolysis) → 2 Lactate (via LDH, regenerating NAD⁺)
• Net yield: 2 ATP per glucose
• Lactate exits into the bloodstream

• Lactate enters → oxidised back to Pyruvate (via LDH)
• Pyruvate → Glucose via gluconeogenesis
• Glucose released back into blood
• Net cost: 6 ATP per glucose synthesised

Diagrams

ATP Energy Balance - the "Metabolic Debt"

Tissues Involved

• Lactate producers: Exercising skeletal muscle, red blood cells (no mitochondria so always anaerobic), white blood cells, intestinal mucosa, skin, brain astrocytes
• Lactate consumers (gluconeogenesis): Liver (primary), kidney cortex (especially during prolonged fasting)
• Other lactate consumers (oxidation): Heart muscle, resting skeletal muscle, brain neurons (fed by astrocytes)

Physiological Significance

1. Prevents lactic acidosis during intense exercise - lactate is constantly cleared by the liver rather than accumulating.
2. Maintains blood glucose during exercise and fasting - lactate is the second most important gluconeogenic substrate after amino acids.
3. Recycles carbon skeletons - no carbon is lost; the same 6-carbon glucose backbone shuttles back and forth.
4. Allows tissues without mitochondria (RBCs) to function - they are obligate glycolysers and depend on the liver to regenerate glucose from their lactate output.

Related Cycle - the Glucose-Alanine Cycle

"The cycling of lactate and glucose between peripheral tissues and liver is called the Cori cycle."

• Basic Medical Biochemistry: A Clinical Approach, 6e, p. 805

Epimers

Diagrams

The Classic Examples

How to Spot an Epimer (Fischer Projection)

C-1  CHO
C-2  H  — OH      ← swap here → Mannose (C-2 epimer)
C-3  HO — H
C-4  H  — OH      ← swap here → Galactose (C-4 epimer)
C-5  H  — OH
C-6  CH₂OH

Epimers vs Anomers - Important Distinction

Biological Significance

• Galactose (C-4 epimer of glucose) must be converted to glucose-1-phosphate via the Leloir pathway (involving UDP-galactose 4-epimerase) before it can enter glycolysis. Failure of this conversion causes galactosaemia.
• Mannose (C-2 epimer of glucose) is converted to mannose-6-phosphate → fructose-6-phosphate (via phosphomannose isomerase) to enter glycolysis. Mannose is important in N-linked glycoprotein synthesis.
• Epimerases are the enzymes that interconvert epimers by inverting the -OH configuration at a specific carbon (e.g., UDP-galactose 4-epimerase, phosphomannose isomerase).

"Carbohydrate isomers that differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon) are defined as epimers of each other."

• Biochemistry 8th ed. Lippincott Illustrated Reviews, p. 257