Proteoglycans, Glycoproteins, and Mucopolysaccharidoses

Vocabulary practice flashcards covering proteoglycan and glycoprotein biochemistry, biosynthesis pathways, lysosomal targeting, and lysosomal storage disorders including mucopolysaccharidoses (Hurler and Hunter syndromes), Pompe disease, I-cell disease, and Chédiak-Higashi syndrome.

Proteoglycan

A macromolecule composed of a core protein ($5\%$) covalently linked to numerous glycosaminoglycan (GAG) side chains ($95\%$) that functions in water binding, shock absorption, and structural support.

Aggrecan

A large proteoglycan found in cartilage that forms aggregates with hyaluronic acid to provide shock absorption and withstand compressive forces.

Decorin

A small proteoglycan that binds to collagen fibrils and regulates fibril assembly.

Glycosaminoglycans (GAGs)

Unbranched heteropolysaccharide chains composed of repeating disaccharide units ($[\text{acidic sugar} - \text{amino sugar}]_n$) that form a gel-like matrix responsible for the body's ground substance.

Repeating Disaccharide Unit of GAGs

The structural backbone of glycosaminoglycans consisting of an amino sugar (D-glucosamine or D-galactosamine) paired with an acidic sugar (D-glucuronic acid or L-iduronic acid).

Keratan Sulfate

A glycosaminoglycan found in the cornea, bone, and cartilage that is unique among GAGs because it contains galactose instead of an acidic sugar.

Hyaluronic Acid (Hyaluronan)

A large, shock-absorbing glycosaminoglycan found in synovial fluid, vitreous humor, and loose connective tissue that is neither sulfated nor covalently bound to a core protein.

Chondroitin Sulfate

The most abundant glycosaminoglycan in the body, primarily localized in cartilage, bone, and heart valves.

Dermatan Sulfate

A glycosaminoglycan found in skin, blood vessels, and heart valves, composed of repeating units of L-iduronic acid and N-acetyl-D-galactosamine.

Heparin

A heavily sulfated intracellular glycosaminoglycan found inside granules of mast cells lining the arteries of the lungs, liver, and skin that acts as an anticoagulant.

Heparan Sulfate

An extracellular glycosaminoglycan found in basement membranes and on cell surfaces that contains higher levels of acetylated glucosamine and less sulfation than heparin.

Proteoglycan Aggregates

Large complexes formed when proteoglycan monomers non-covalently associate with a central hyaluronic acid chain via small link proteins.

Glycosyltransferases

A family of Golgi-resident enzymes that catalyze the elongation of glycosaminoglycan polysaccharide chains through the sequential placement of UDP-sugar derivatives.

Fibronectin

An extracellular matrix glycoprotein that binds collagen and integrins to regulate cell migration during embryogenesis and mediate fibrin cross-linking during hemostasis.

Laminin

A major non-collagenous glycoprotein organizer of the basal lamina that binds to type IV collagen, integrins, and proteoglycans.

N-glycosylation

A form of protein glycosylation in which carbohydrate chains are attached to the amide nitrogen atom of an asparagine side chain.

O-glycosylation

A form of protein glycosylation in which sugar chains are linked to the hydroxyl oxygen atom of a serine, threonine, hydroxylysine, or hydroxyproline residue.

Dolichol Pyrophosphate

A membrane-bound lipid carrier in the rough endoplasmic reticulum upon which branched oligosaccharide cores are assembled before transfer to asparagine residues.

N-acetylglucosamine-1-phosphotransferase

The Golgi enzyme that phosphorylates mannose residues on precursor lysosomal proteins to direct their transport to lysosomes.

Mannose-6-Phosphate (M6P)

A phosphorylated carbohydrate tag generated in the Golgi apparatus that targets newly synthesized acid hydrolases to the lysosomes.

Mucopolysaccharidoses (MPSs)

A group of hereditary lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans, leading to their progressive accumulation in tissues.

Hurler Syndrome (MPS I H)

A severe autosomal recessive mucopolysaccharidosis caused by $\alpha$-L-iduronidase deficiency, leading to dermatan and heparan sulfate accumulation, corneal clouding, skeletal deformities, and early death from cardiac complications.

$\alpha$-L-Iduronidase

The lysosomal enzyme deficient in Hurler syndrome (MPS I H) that is required for the catabolism of dermatan sulfate and heparan sulfate.

Hunter Syndrome (MPS II)

An X-linked recessive mucopolysaccharidosis caused by iduronate sulfatase deficiency that causes dermatan and heparan sulfate storage, physical deformity, and aggressive behavior without corneal clouding.

Iduronate Sulfatase

The lysosomal enzyme deficient in Hunter syndrome (MPS II) that hydrolyzes sulfate groups from iduronic acid units.

Pompe Disease (GSD Type II)

A lysosomal storage disorder caused by a deficiency in lysosomal acid maltase ($\alpha\text{-1,4-glucosidase}$), leading to glycogen vacuole accumulation in cardiac muscle, skeletal muscle, and the liver.

Acid Maltase ($\alpha\text{-1,4-glucosidase}$)

The lysosomal enzyme that degrades small fractions of cellular glycogen at an acidic $\text{pH of } 5$, whose deficiency results in Pompe disease.

I-Cell Disease (Mucolipidosis Type II)

A severe genetic disorder caused by mutations in the gene for N-acetylglucosamine-1-phosphotransferase, resulting in absent lysosomal M6P targeting, leakage of hydrolases into extracellular fluids, and dense intralysosomal inclusion bodies.

Chédiak–Higashi Syndrome

An autosomal recessive disease caused by mutations in the lysosomal trafficking regulator gene (LYST), resulting in impaired microtubule polymerization, defective phagolysosome fusion, giant granules in leukocytes, and recurrent pyogenic infections.

LYST Gene

The lysosomal trafficking regulator gene that is mutated in Chédiak–Higashi syndrome, impairing microtubule polymerization and leukocyte degranulation.

Enzyme-Replacement Therapy (ERT)

A treatment strategy based on periodic intravenous infusions of recombinant enzymes bearing mannose-6-phosphate residues, which enter target cells through surface M6P receptors to clear accumulated substrates in lysosomes.