Carbohydrate Biochemistry Overview

Synthesis of Glycosides, Lactose, Glycoproteins & Glycolipids

• Carbohydrates have diverse functions beyond being energy sources.
• Some carbohydrates aren't found in the diet and must be synthesized.

Carbohydrate Functions

• Lactose: A disaccharide synthesized in the mammary gland, providing energy for offspring.
• Glycosides: Sugars attached to non-sugar entities (e.g., glycoproteins, glycolipids).
• Glycoproteins: Attached to N or O groups on extracellular proteins (N- and O- glycosylation).
• Glycolipids: Carbohydrates attached to lipids, located on cell membrane exteriors; act as recognition factors (e.g., glycero- and sphingo-glycolipids).

Precursor UDP-Glucose

• UDP-glucose is formed from glucose-1-phosphate (G1P).
• It's an "activated sugar" with various roles.
  • Glycogen synthesis
  • Attachment to proteoglycans, glycoproteins, or glycolipids.
  • Conversion to UDP-glucuronate (precursor for polysaccharides).
  • Synthesis of lactose.

Glycosyltransferases

• Sugars are transferred during glycoprotein/proteoglycan synthesis from nucleotide sugars to nucleophilic amino acid residues (serine, threonine, and asparagine).
• The sugar-residue bond is a glycosidic bond.
• Glycosyltransferases catalyze these reactions.
• Glycosyltransferases have important roles in development and mutations can cause diseases.
• Bacteria use glycosyltransferases, making them targets for antibiotic inhibitors.

Metabolic Routes of UDP-Glucuronate

• UDP-glucuronate is a crucial product from UDP-glucose.
• It's a substrate for proteoglycans and glycoproteins, as well as other sugars and glycosides (steroids and xenobiotics).
  • Xenobiotics: Substances not naturally produced by humans (drugs or carcinogens).

Formation of Glucuronides

• UDP-glucose is converted to UDP-glucuronate by UDP-glucose dehydrogenase (producing 2 NADH).
• UDP-glucuronate is converted to glucuronide by UDP-glucuronate transferase (forming a glycosidic bond).
• Glucuronide is water-soluble, facilitating removal of nonpolar substances (drugs, xenobiotics) in urine or bile.

Some Compounds Degraded and Excreted as Urinary Glucuronides

• Several compounds are processed into glucuronides for excretion, including steroids, hormones, and xenobiotics.
  • Examples: estrogen, progesterone, triiodothyronine, acetylaminofluorene, meprobamate, and morphine.
  • Testosterone is also excreted as a glucuronide.

How to Beat Drug Testing

• Methods to cheat drug tests, including using alternative urine, adulterating the sample, using diuretics, and inhibiting enzymes that make UDP-drug conjugates are not discussed in detail as they are ethically questionable and illegal.

Steroids

• Green and white teas suppress UDP-glucuronosyltransferase UGT2B17, affecting testosterone glucuronidation.

Formation of Bilirubin Diglucuronide

• Bilirubin is a heme degradation product (from myoglobin, hemoglobin, cytochromes).
• Adding hydrophilic glucuronate groups makes bilirubin soluble and excretable.
• Bilirubin accumulation causes jaundice (yellowing of skin and eyes).
• Phototherapy converts bilirubin to a more soluble form.

Synthesis of Lactose

• Lactose (milk sugar) is a disaccharide of galactose and glucose.
• Lactose is generally formed from UDP-glucose in two steps:
  • Epimerase converts the glucose moiety to galactose.
  • Lactose synthase attaches galactose to the C4 of glucose (forming a β(1→4) glycosidic linkage)

Pathways for Interconversion of Sugars

• Complex pathways allow for multiple potential uses of glucose.
• Glucose can form glycoproteins, glycolipids, glycosaminoglycans (e.g., heparin), or sialic acid.
  • Sialic acid serves as an influenza receptor.

N-Glycosylation

• Glycoproteins have complex carbohydrate branches (e.g., N-acetylneuraminic acid, galactose, N-acetylglucosamine, mannose, fucose).
• Carbohydrate sequence resembles amino acid sequence.

Fates of Glycoproteins & Proteoglycans

• Glycoproteins are created in the endoplasmic reticulum (ER), then secreted from the Golgi to the plasma membrane.
• They often act as receptors on cell surfaces.
• Some glycoproteins are secreted or transported to lysosomes, with glycosyl groups protecting proteins from lysosomal enzymes.

Carbohydrates & Influenza

• 1918 flu pandemic caused ~100 million deaths worldwide.
• Influenza entry and exit involve sialic acid-containing receptors on cells.
• Treatment targets viral neuraminidase (an enzyme that degrades sialic acid and allows egress).

Carbohydrates and Blood Groups

• Carbohydrates on red blood cells determine blood type (A, B, AB, or O).
• Different blood types have specific carbohydrate antigens and corresponding antibodies.
• Blood type compatibility is critical for blood transfusions.

Blood Groups-Continued

• The antigenic determinant is the portion of the carbohydrate structure responsible for blood type specificity.
• Other blood groups exist, determined by other carbohydrate patterns (e.g., Rh).
  • Common terms: Galactose, N-acetylgalactosamine, N-acetylglucosamine, and fucose.

This quiz covers the synthesis and functions of important carbohydrates such as glycosides, lactose, glycoproteins, and glycolipids. Explore how UDP-glucose serves as a precursor in various biochemical processes, including energy provision and cellular recognition. Test your knowledge on the diverse roles of these complex molecules.