Glycolipids and Glycoproteins Lecture Oct 3

Question 1

How does the body synthesize lactose for fuel when a woman is breast feeding?

Answer 1

It uses the enzyme lactose synthase, which is a dimer of galactosyltransferase and alpha-lactalbumin

It takes UDP-galactose and glucose and combines them to form lactose.

***NOTE: Normally galactosyltransferase acts as a monomer to attach galactose to glycoproteins, but the lactalbumin is upregulated after a woman gives burth and it combines with the galactosyltransferase to provide it additional substrate specificity for glucose

Question 2

Describe the breakdown process for heme.

Answer 2

Decylizing heme oxygenase (using NADPH and O2) cleaves heme between the A and B rings to form biliverdin (which is green)

Biliverdin is then reduced to bilirubin by biliverdin reductase. Bilirubin is yellow

Question 3

Describe the removal process for bilirubin?

Answer 3

Bilirubin is not very soluble so it has to be transported in the blood bound to albumin.

In the liver, the blirubin is glycosylated by the addition of 2 gluconarates in the form of UDP glucaronate. THis is catalyzed by glucaronosyl trasnferase

the bilirubin diglucuronide is more soluble and can be excreted in bile or urine

Question 4

What causes jaundice?

Answer 4

If the glucuronidation of the bilirubin doesn’t occur, the bilirubin will diffuse out of circulation into the tissues, causing yellowing of the eye sand skin

This can be from having an immature glucuronate conjugatin system (for neonates)

It can be from excessive RBC desctruction - hemolytic jaundice

It can be from liver damage - Hepatocellular jaundice

And it can be from a blockage of bile drainage - obstructive jaundice

Question 5

What sugars are added to lipid sand proteins as UDP conjugates first?

Answer 5

glucose

galactose

xylose

N-acetylglucosamine

N-acetylgalactosamine

Question 6

WHat 2 sugars are attached to lipids and proteins as GDP conjugates first?

Answer 6

mannose and L-fucose

Question 7

What do glycolipids do?

What do glygoproteins do?

What do proteoglycans do and how are they different from glycoproteins?

Answer 7

Glycolipids are lipids with sugars - they sit in the membrane with sugar moities facing the noncytosolic side - antigens, recognition motifs, and receptors.

Glycoproteins are proteins with sugars that either sit in the plasma membrane, in lysosomes (glycocalyx), or secreted into the blood or ECM

PRoteoglycans are proteins with sugars but the sugar content vastly outweights the protein content. These are almost exclusively part of the ECM - very important in cartilage

Question 8

How is salivary mucin modified to increase the viscosity of water?

Answer 8

It is modified by hthe addition of N-acetylglucosamine and N-acetylneuraminic acid (NANA)

THe NAN hydrogen bonds with water to make it effectively larger

Question 9

WHere are glycoproteins glycosylated?

Answer 9

In the ER lumen

Question 10

What are glycoproteins’ role in the lysosome?

how do they get sent there from the ER?

Answer 10

They are often the hydrolytic enzymes

They are directed there by the mannose-6-phosphate tag

Mannose 6 phosphate receptors in the golgi bind to the glycoprotein and directs them to lysosome

Question 11

What are cerebrosides?

Globosides?

Gangliosides?

WHat do they use for a backbone?

Answer 11

They all use serine for a backbone, which becomes sphingosine, then ceramide.

A cerebroside is ceramide with 1 sugar (either glucose or galactose)

A globoside has 2 or more sugars

A ganglioside has an oliogosaccharide, plus NANA

Question 12

Where are cerebrosdies and gangliosdies often found in the body?

Answer 12

in the membranes surrounding neuron sheaths

Question 13

In general, what causes lysosomal storage diseases?

Answer 13

An inability to degrade the carbohydrate chains of gangliosides in lysosomes because of a lack of hydrolase enzymes.

Question 14

Which hydrolytic enzyme is responsible for breaking down gangliosides?

What are the two forms?

Answer 14

Hexosaminidase

It comes in two forms:

Hexosaminidase A (trimer of 1alpha and 2 beta)

and Hexosaminidase B (homotetramer of 4 beta)

Question 15

What causes Tay-Sachs disease?

Answer 15

A defective gene in the alpha subunit of hexosaminidase. This means that hexosaminidase A is the only one that’s defective. B would still be active because it only has beta subunits.

This causes an inability to cleave off N-Acetyl-D-galactose from the galngioside.

This means the ganglioside builds up in the neurons, destroying cell function

TaySachs is characterized by mental retardation and motor impariment, blindness, deafness, and spastic. Most die by age 3

(higher in ashkenazi jews)

Question 16

What causes Sandhoff disease?

Answer 16

The defective gene is the beta subunit of hexosaminidase, so this affects both hexosaminidase A and B.

Again, yo ucan’t reduce the glangliosides and globosides in the lysosomes and they buildup, destroying cell function.

Question 17

Which is more severe? Tay-Sachs or Sandhoff?

Answer 17

Sandhoff because both hexosaminidase A and B are defective.

It has an earlier and mroe severe onset.

Question 18

What causes Gaucher disease? How is it treated?

Answer 18

This is a defect in beta-glucosidase. So you can’ clave the glusoe off of the cerebroside.

This results in accumulation of glucocerebreside in brain, liver, bone marrow, and spleen.

Gaucher disease can be treated effectively with infusions of recominant beta-glucosidase (imiglucerase)

Question 19

What causes Fabry disease?

Answer 19

This is a deficiency in alpha-galatocerebrosidase (also called alpha-galactosidase)

This means you can’t cleave off the galactose from the the end of Glu-Gal-Gal-Globosides.

This causes an accumulation and failure of the renal, cardiovascular and cerebrovascular system.

This can be treated with enzyme replacement therapy though - Agalsidase.