Carbohydrate Chemistry

1. Classification

By Carbon Number

By Carbonyl Group

• Aldoses - have an aldehyde (-CHO) as the carbonyl group (e.g., glucose, galactose)
• Ketoses - have a keto (C=O) group (e.g., fructose, ribulose)

By Polymer Length

• Monosaccharides - single sugar units
• Disaccharides - 2 units (e.g., lactose, sucrose, maltose)
• Oligosaccharides - 3-10 units (mostly not digested by human enzymes)
• Polysaccharides - >10 units, can be hundreds of residues (starch, glycogen, cellulose)

2. Structure of Glucose - Three Representations

3. Stereochemistry and Isomerism

D- and L-Isomers (Enantiomers)

• The designation D or L is based on the orientation of the -OH on the asymmetric carbon farthest from the carbonyl carbon (C-5 in a hexose)
• D-isomer: -OH on the right in a Fischer projection
• L-isomer: -OH on the left
• Virtually all biologically active monosaccharides in humans are D-isomers
• Most enzymes are stereospecific for either D or L forms; isomerases can interconvert them

Epimers

• Compounds that differ in configuration around only one carbon (not the carbonyl carbon) are epimers
• Glucose and galactose are C-4 epimers (differ at C-4 only)
• Glucose and mannose are C-2 epimers (differ at C-2 only)

Optical Activity

• D/L designation refers to spatial configuration, not direction of light rotation
• Glucose is dextrorotatory (+), sometimes called "dextrose"
• Fructose is levorotatory (-), so it is D(-)-fructose
• Hydrolysis of sucrose yields an "invert sugar" because the strongly levorotatory fructose inverts the dextrorotatory action of sucrose

4. Ring Structures (Cyclization)

• Pyranose - 6-membered ring (5C + 1O), analogous to pyran; over 99% of glucose in solution
• Furanose - 5-membered ring (4C + 1O), analogous to furan; common form of fructose and ribose

Anomeric Carbon and Anomers

• Cyclization makes the former carbonyl carbon asymmetric - this is the anomeric carbon
• Creates two new diastereomers called α and β anomers:
  • α form: -OH on the anomeric carbon is axial (same side as the ring in a modified Fischer projection; trans to CH₂OH in Haworth)
  • β form: -OH on the anomeric carbon is equatorial (opposite side)
• For glucose: α form = 36%, β form = 64% at equilibrium

Mutarotation

• The α and β anomers interconvert spontaneously in solution through the open-chain form
• This process is called mutarotation
• Biologically, the anomeric configuration matters: glycogen is built from α-D-glucopyranose; cellulose is built from β-D-glucopyranose

5. Reducing Sugars

• If the anomeric carbon is free (not involved in a glycosidic bond), the ring can open, exposing the aldehyde group
• This aldehyde can reduce chromogenic agents like Benedict's reagent (Cu²⁺ is reduced, changing color)
• All monosaccharides are reducing sugars
• Among disaccharides: lactose and maltose are reducing (one free anomeric -OH); sucrose is non-reducing (both anomeric carbons are engaged in the glycosidic bond)
• Fructose (a ketose) is also a reducing sugar because it isomerizes to an aldose

Clinical note: A positive Benedict's test in urine indicates glycosuria, which is not normal and warrants follow-up testing to identify the specific sugar.

6. Glycosidic Bonds

• Named by the carbons involved and the anomeric configuration: e.g., β(1→4) linkage in lactose (C-1 of β-galactose joined to C-4 of glucose)
• α(1→4) bonds: found in starch (amylose, amylopectin), glycogen, and maltose
• α(1→6) bonds: branch points in glycogen and amylopectin
• β(1→4) bonds: found in cellulose and lactose
• α(1→2)β bond: sucrose (both anomeric carbons engaged)

N- and O-Glycosidic Bonds to Non-Carbohydrates

• N-glycosidic bond: sugar links to -NH₂ group (e.g., nucleosides, N-linked glycoproteins)
• O-glycosidic bond: sugar links to -OH group (e.g., O-linked glycoproteins, steroids)

7. Important Monosaccharide Derivatives

8. Important Disaccharides

9. Polysaccharides

Starch (Plant Storage)

• Amylose (13-20%): linear, unbranched helical chain of glucose with α(1→4) linkages
• Amylopectin (80-87%): branched; chains of 24-30 glucose residues with α(1→4) in chains and α(1→6) at branch points

Glycogen (Animal Storage - "Animal Starch")

• More highly branched than amylopectin; chains of 12-15 glucose residues with α(1→4) links and α(1→6) branch points
• Liver glycogen: maintains blood glucose between meals
• Muscle glycogen: local fuel for contraction
• Rapidly mobilized by phosphorylase

Cellulose (Plant Structural)

• Linear polymer of glucose with β(1→4) linkages
• Humans cannot digest cellulose (no β(1→4)-glucosidase)
• Major component of dietary fiber

Inulin

• Polymer of fructose; found in artichokes, dahlias, chicory
• Not hydrolyzed by intestinal enzymes; no caloric value
• Used clinically to measure GFR (glomerular filtration rate)

10. Digestion of Dietary Carbohydrates

• Final products (glucose, galactose, fructose) are absorbed by enterocytes via specific transporters (SGLT-1 for glucose/galactose, GLUT-5 for fructose)

11. Clinically Relevant Points

• Lactase deficiency (lactose intolerance): undigested lactose fermented by colonic bacteria → gas, osmotic diarrhea, bloating. Very common (up to 70% of adults globally)
• Sucrase-isomaltase (SI) deficiency: intolerance to sucrose; affects up to 9% of Americans of European descent; treated with dietary restriction and enzyme replacement
• Glycosuria (reducing sugar in urine): positive Benedict's test is pathological; requires follow-up for diabetes, galactosemia, or other metabolic disorders
• Glycemic index: reflects how rapidly a starch raises blood glucose; determined by digestibility and cooking
• Glycogen storage diseases (e.g., von Gierke, Pompe, McArdle diseases): enzyme defects in glycogen synthesis or breakdown