Carbohydrates

Introduction to Carbohydrates

  • Lecture by Emily Flack on molecular biology and biochemistry including carbohydrates.

Learning Outcomes

  • Understand various functions of carbohydrates in both prokaryotic and eukaryotic cells.

  • Describe chemical structures and properties of carbohydrates.

  • Appreciate the biological significance of glycosylation and the challenges associated with its study.

Biological Roles of Carbohydrates

  • Importance in biological processes, despite common misconceptions about sugar significance.

Abundance of Carbohydrates

  • Account for 2% of the mass of mammalian cells, primarily in the form of polysaccharides.

  • Approximately 1% of the human genome encodes for proteins involved in glycosylation.

Functions of Carbohydrates

  • In the Liver:

    • Storage as Glycogen, conversion into glucose, and involvement in glycolysis and ATP production.

  • In Muscle:

    • Energy roles in glycolysis, lactate conversion, etc.

  • In Bacteria:

    • Structural components such as the Gram-positive and Gram-negative bacterial cell walls, involving peptidoglycan and lipoteichoic acid.

Glycobiology

  • Focuses on the study of carbohydrate structure, biosynthesis, and functions, addressing their pervasive roles in biology.

The Glycocalyx

  • Describes carbohydrates as a 'sugar coat' on cells, influencing cell interactions and signaling.

Carbohydrates and Disease

  • Glycans are integral to the pathophysiology of numerous diseases, highlighting how knowledge of glycoscience can advance human health research.

  • Referenced the contributions of Professor Carolyn Bertozzi in glycoscience and its relevance in cancer research.

Definition of Carbohydrates

  • Traditionally classified as "hydrated carbon" with the empirical formula Cn(H2O)n.

  • Example: Glucose has the formula C6H12O6, includes one carbonyl group (C=O) and multiple hydroxyl groups (OH).

Structural Diversity of Monosaccharides

  • Monosaccharides vary significantly, are often derivatized with functional groups such as N, S, or P.

  • Common monosaccharides have 4-9 carbon chains, with considerable diversity found in bacterial monosaccharides.

Stereochemistry: Anomers

  • Anomers defined based on the configuration at the anomeric carbon (C1) relative to the highest numbered stereocenter (C5).

  • Utilizing Haworth projections to visually represent stereochemistry.

Cyclization and Mutarotation

  • Cyclization: Processes by which open-chain carbohydrates form ring structures through reaction between hydroxyl and carbonyl groups.

  • Mutarotation: The free hydroxyl at the anomeric position allows interconversion between anomers; however, this does not occur once a glycosidic bond forms.

Glycosidic Bond Formation

  • Involves condensation reactions at various positions due to multiple hydroxyl groups, allowing numerous possible structures (di-, tri-, tetra-, and oligosaccharides).

Complexity and Structural Diversity of Carbohydrates

  • Carbohydrates possess significant structural complexity compared to nucleic acids and proteins, allowing for a vast range of polymers.

  • Examples include a potential of over 17 million unique sequences for glycans made from a set number of monomers.

Common Glycoconjugates

  • Proteins, glycoproteins, and proteoglycans distinguished by various linkage types and structural variations of glycans.

Glycoconjugates Specifics

  • Predicting glycosylation based on protein sequence—O-glycosylation at Ser/Thr and N-glycosylation at Asn.

  • Glycosylation reliant on experimental determination as it is not template-driven.

Challenges in Glycoscience

  • Key issues include identifying potential glycosylation sites, understanding what they are glycosylated with, and what interactions occur.

Biological Significance of Glycosylation

  • Investigates the nature of glycan interactions and their biological implications in health and disease.

Insights from Glycoscience Publications

  • Emphasizes the necessity of integrating glycoscience into genomic and proteomic research to improve human health outcomes.

SARS-CoV-2 Spike Protein and Glycosylation

  • The spike protein model demonstrates the importance of glycosylation in virus-receptor interactions, especially in terms of immune evasion by creating a glycan shield.

Importance of Understanding Glycosylation in SARS-CoV-2

  • Investigations uncover the role of N-glycans in shielding the spike protein, impacting its recognition by antibodies.

Conclusion on Carbohydrate Complexity

  • The structural diversity and complexity of carbohydrates lead to a multitude of terms and functions, underscoring their importance in biology.

Glossary

  • Monosaccharide: Single sugar unit (e.g., glucose).

  • Disaccharide: Two sugar units linked together.

  • Oligosaccharide: More than two sugar units.

  • Carbohydrate: Refers to the range from monosaccharide to oligosaccharide.

  • Glycoside: Carbohydrate with an anomeric substituent other than OH.

  • Glycoconjugate: General term for carbohydrate linked to a biomolecule.