biosynthesis and degradation of other macromolecules and associated abnormalities, complex carbohydrates (eg, lysosomal storage disease), glycoproteins, and proteoglycans (eg, type II glycogen storage disease)

Lysosomal storage diseases

lysosomal storage diseases

Sphingolipids

  • Derived from sphingosine
  • Ceramide
    • The parent compound for other sphingolipids.
    • Fabry's disease: lack α-galactosidase A, accumulates ceramide trihexoside. Peripheral neuropathy, angiokeratomas, cardiovascular/renal disease.
  • Sphingomyelin
    • Most common sphingolipid = ceramide + phosphocholine or phosphoethanolamine.
    • Niemann-Pick disease: lack sphingomyelinase, accumulates sphingomyelin. A type of leukodystrophy. Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells.
  • Cerebroside
    • Galactocerebrosides are found in brain neurons.
      • Krabbe's disease: lack galactocerebrosidase, accumulate galactocerebroside. A type of leukodystrophy, disrupts myelin sheath. Peripheral neuropathy, developmental delay, optic atrophy, globoid cells.
      • Sulfate at 3 position of galactose form cerebroside sulfate.
      • Metachromatic leukodystrophy: lack arylsulfatase A, accumulate cerebroside sulfate, disrupt myelin sheath. Central and peripheral demyelination with ataxia, muscle wasting, dementia.
    • Glucocerebrosides are found elsewhere.
      • Gaucher's disease: lack β-glucocerebrosidase, accumulate glucocerebroside. Hepatosplenomegaly, aseptic necrosis of femur, bone crisis, Gaucher's cells. In less severe cases, patients fatigue and bruise easily. In severe cases, there's extensive brain damage.
  • Ganglioside
    • Sphingoglycolipids with sialic acid (N-acetylneuraminic acid) as one of its sugar residues.
    • Most prevalent in brain.
    • Tay Sachs: lack hexosaminidase A, accumulate GM2 ganglioside. Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin. Prevalent in Eastern European and Askhenazi Jewish population.

Oligosaccharides and Polysaccharides

  • Sugars are joined by the glycoside bond (acetal in organic chemistry) to make oligosaccharides.
  • Lactose = galactose + glucose (β 1-4 linkage).
    • Lactose synthase: UDP-galactose + glucose → Lactose + UDP
    • Secreted in milk.
    • Broken down by lactase.
  • Sucrose = glucose + fructose (α 1-2)
  • Maltose = glucose + glucose (α 1-4). It's basically starch broken down into disaccharide.
  • Isomaltose = maltose but with α 1-6 linkage.
  • Cellobiose = glucose + glucose (β 1-4). It's basically cellulose broken down into disaccharide. We can't digest cellulose or cellobiose.
  • Starch
    • Amylose = glucose α 1-4 polymer. Broken down by amylase.
    • Amylopectin = amylose with α 1-6 branches. Debranching enzyme needed to break α 1-6 linkage.
  • Glycogen = more branched than amylopectin = glucose α 1-4 polymer with α 1-6 branches.
    • Broken down by phosphorylase and debranching enzyme.
    • Made by synthase and branching enzyme.
    • Type II glycogen storage disease, aka Pompe's disease = lack lysosomal α 1-4 glucosidase.
  • Plant polymers
    • Cellulose = glucose β 1-4 polymer. Found in fiber. Broken down by cellulase, but we don't have this enzyme.
    • Pectin = galacturonic acid α 1-4 polymer. Extracted from plants, used in gelling agents, like jelly.
  • Chitin = N-acetylglucosamine β 1-4 polymer. Found in mushrooms and the shells of shrimps and lobsters.
  • Peptidoglycan = bacteria cell wall
    • N-acetylglucosamine + N-acetylmuramic acid (β 1-4).
    • Cross-linked by amino acids chains.
  • Glycosaminoglycan = mucopolysaccharides = polymer of amino sugar with sulfate/carboxylate.
    • Found in ground substance (gel-like matrix) of connective tissue.
    • Chondroitin sulfate and keratan sulfate are components of connective tissue. Chondroitin sulfate and glucosamine sulfate are used to treat damaged cartilage.
    • Heparin = anticoagulent. Found in mast cells lining arterial walls.
    • Hyaluronic acid = vitreous humor and synovial fluid. Degraded by hyaluronidase.
    • Dermatan = found in skin.
    • Hurler's syndrome: lack α-L-iduronidase, accumulate Heparan sulfate, dermatan sulfate. Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly.
    • Hunter's syndrome: lack iduronate sulfatase, accumulate heparan sulfate, dermatan sulfate. Mild Hurler's syndrome.

Glycoproteins

  • Antibodies.
  • Antigenic determinants
    • ABO blood group is due to oligosaccharide differences on the cell surface glycoproteins.
  • N-linked: glycoside (acetal) bond of sugar to asparagine.
    • Cotranslational synthesis
      1. Link oligosaccharide to lipid (dolichol).
      2. Transfer oligosaccharide to translating peptide by oligosaccharyltransferase.
      3. Remove some sugar units.
      4. Add some sugar units.
  • O-linked: glycoside (acetal) bond of sugar to serine of threonine.
    • Posttranslational synthesis
      • Addition of sugars in the Golgi
      • Starts off with addition of N-acetylgalactosamine (GalNAc) by GalNAc transferase.
    • 5-Hydroxylysine in collagen.
  • GPI anchor = C-term of peptide + phosphoethanolamine + core tetrasaccharide + phosphatidylinositol = anchors protein to membrane.

Proteoglycans

  • Core protein + glycosaminoglycan chains.
  • High carbohydrate content (~90% by weight).
  • Sugars added as this glycoprotein travels through the golgi network.
  • Deficiency in lysosomal enzymes lead to accumulation of proteoglycans, which lead to Hurler's syndrome.
  • Cartilage proteoglycan = core protein + chondroitin = gives resilience.

Eicosanoids

eicosanoids

Cholesterol Biosynthesis

cholesterol biosynthesis

Phospholipids

phospholipids
  • Aka. glycerophospholipids or phosphoglycerides.
  • Found in cell membranes.
  • Plasmalogen = phospholipid with unsaturated ether linkage at C1 (opposite to phosphate carbon) instead of an ester.