Lecture 17 - Intro to Complex Carbohydrates

Question 1

Proteoglycans

Answer 1

• A protein with covalently attached glycosaminoglycans (mucopolysaccharides): chondroitin sulfate, keratan sulfate, heparan sulfate. Glycosaminoglycans are the sugar part of a proteoglycan
• Glycosaminoglycans are negatively charged
• Proteoglycans function as tissue and extracellular matrix organizers, lubricants at joints, and also function in the mediation of growth factors.
• Either secreted into the extracellular matrix or are integral membrane proteins

Question 2

Six types of glycosaminoglycans associated with proteoglycans

Answer 2

• hyaluronic acid
• chondroitin sulfates
• dermatan sulfate
• heparan sulfate
• heparin
• keratan sulfates
• GAGs are typically composed of repeating disaccharides units
• Except for hyaluronic acid, GAGs are generally sulfated. The high negative charge conferred by sulfation is important for GAG function
• Clinical Correlation: Heparin has the highest negative charge of any know molecule and can function as an anti-coagulant

Question 3

Mucopolysaccharidoses

Answer 3

• A group of genetic disorders characterized by accumulation and excretion (urine) of oligosaccharides from glycosaminoglycans (mucopolysaccarides)
• Cause skeletal abnormalities and mental retardation.
• Result from a genetic deficiency in one or a combination of hydrolases that breakdown heparan sulfate, dermatan sulfate, chondroitin sulfate, and keratan sulfate

Question 4

Hunter Syndrome (accumulated products/enzyme deficiency)

Answer 4

• Heparan sulfate, Dermatan sulfate

- Iduronate sulfatase

Question 5

Hurler-Scheie Syndrome (accumulated products/enzyme deficiency)

Answer 5

• Heparan sulfate, Dermatan sulfate

- Iduronidase

Question 6

Sanfilippo Syndrome (accumulated products/enzyme deficiency)

Answer 6

• Heperan sulfate
• Type A: Heparan sulfamidase
• Type B: N-Acetylglucosaminidase
• Type C: Acetyl CoA: α-glucosaminide acetyl transferase
• Type D: N-Acetylglucosamine 6-sulfatase

Question 7

Morquio Syndrome (accumulated products/enzyme deficiency)

Answer 7

• Type A: Keratan, Chondroitin sulfate/Galactose-6-sulfatase

- Type B: Keratan Sulfate/β-Galactosidase

Question 8

Biosynthesis of N-Linked Glycoproteins

Answer 8

• There is no DNA template for N- or O-linked glycans.
• The basic N-linked glycan attached in the ER is modified in the Golgi apparatus by glycosidases and glycosyltransferases that remove and add monosaccharides, respectively
• Dolichol is a precursor molecule involved in N-linked glycan biosynthesis
• The diversity and complexity of N-linked glycans is determined by the population of glycosidases and glycosyltransferases unique to each cell type
• Altered glycosylation is a hallmark of cancer progression

Question 9

Chondrodystrophies (Dwarfism)

Answer 9

• Characterized by a normal-sized trunk with abnormally shortened limbs and extremities, and early onset of osteoarthritis.
• Chondrodystrophy can be caused by improper sulfation during the biosynthesis of glycosaminoglycans.
• Normal sulfation of glycosaminoglycans involves the transport of inorganic sulfate across the plasma membrane and its conversion to phosphoadenosyl-phosphosulfate (PAPS) by PAPS synthetase.
• A number of genetic deficiencies in the sulfate transporter or PAPS synthetase results in diminished sulfation of glycosaminoglycans such as chondroitin sulfate.

Question 10

O-Linked Glycoproteins

Answer 10

• O-linked glycans are bound to the hydroxy oxygen of Ser and Thr.
• There are five different core types for O-linked glycans, but all have common GalNAc at the reducing end.
• O-linked glycans are synthesized in the Golgi apparatus