CFB 4: Carbohydrate Structure/Function

Carbohydrates can be based on _________ or _______, which are chemically reactive.

Aldehydes or ketones

Small amounts of linear forms are in equilibrium with what?

Equilibrium with predominant ring structures

99% are in cyclic structures

The anomeric carbon becomes a chiral center that can be __ or __.

α or β

The hydroxyl group goes _____ the plane for α.

Below

Stereochemistry is important -- resulting in "_________" sugars.

Different sugars even though chemically identical

Proteins bind carbohydrates stereospecifically using _______ ________.

Binding domains (CRD/CBD/LECTIN domains)

The anomeric carbon of a saccharide can form a ________ _______.

Glycosidic linkage

Glycosidic linkage

A covalent bond formed between two monosaccharides by a dehydration reaction

Synthesis of lactose involves what?

UDP-D-Galactose

What is needed for biological, enzymatic polysaccharide glycosidic bond formation?

Activated sugar nucleotides

What are the 3 important dietary dissacharides?

Maltose

Lactose

Sucrose

Maltose

Glucose α(1→4) glucose

Lactose

Galactose β(1→4) glucose

Sucrose

Glucose α(1→2) fructose

Amylose is what type of glucose?

Linear poly α(1→4) glucose

Polyglucose can also have what type of branches?

α(1→6)

Polyglucose is what in humans?

Glycogen in humans (amylopectin from plants)

Alpha vs. Beta matters! What is the difference between amylose and cellulose?

Amylose: glucose α(1→4) glucose

Cellulose: glucose β(1→4) glucose

What are glycosaminoglycans (GAGs)?

Long linear repeats

What makes drugs (e.g. Tylenol) or molecules like bilirubin more polar and more excretable?

Conjugation of glucuronic acid

UGT is what?

UDP-α-D-glucuronsyltransferase

Gilbert's Syndrome

UGT deficit leads to high bilirubin

Anomeric carbons form __________ bonds.

Glycosidic

Glycation

Binding of a protein molecule to a glucose molecule resulting in the formation of damaged, nonfunctioning structures

T/F: Glycation is always bad.

Can be good! (e.g. Maillard reaction browns toast)

Glycated hemoglobin (HbA1C) is elevated in what disease?

Diabetes

What does HbA1C provide?

History of glucose levels

Glycoproteins are produced _____________.

Enzymatically

False: Glycoproteins can have a small amount of carbohydrate or be >90% carbohydrate.

True

Glycosylation can be _-linked or _-linked. On which two AAs?

N-linked or O-linked

Asparagine or serine

The enzymes involved in the assembly of the carbohydrate are called what?

Transferases

How are O-linked vs. N-linked sugars added to the protein?

O-linked: one at a time

N-linked: as a block of 14 sugars first assembled on the lipid dolichol phosphate

When does sugar processing occur?

During trafficking through the secretory pathway (ER and Golgi)

Congenital disease of glycosylation (CDGs) result from defects in what?

Processing enzymes

Lysoosmes have both endo- and exo-____________.

Glycosidases

Enzyme deficiencies result in accumulation of what in vesicles that impair function?

Partially degraded material

Mucopolysaccharidoses

I cell disease

Pompe Disease

I cell disease defect

Multiple enzymes

Pompe Disease defect

Acid α glucosidase (single enzyme defect)

A 3 month old child has muscle hypotonia and feeding problems. There is also hepatomegaly and cardiomegaly. Muscle biopsy shows accumulation of polysaccharide in the lysosome. Which enzyme is deficient?

Acidic α-glucosidase

Glycoproteins except for which one are exported out of the cell or have their glycosylated domains oriented out of the cell?

O-GlcNac

Linkages are mostly either N-___ or O-___

N-ASN

O-SER/THR

While O-linked structures are assembled on the protein, the first N-linked transfer to ASN occurs as a 14 sugar structure first assembled on ________ lipid in the __.

Dolichol lipid in the ER

Sugar structures are modified as the glycoproteins move from the __ to through the _____.

ER to Golgi

Cells are coated in what?

Carbohydrates, proteoglycans, or glycolipids

Mucins

Major macromolecular constituents of mucus that provide lubrication and act as a barrier

Most abundant type of mucin in the saliva and oral cavity

Mucin 5B

What are proteoglycans?

Proteins with GAGs attached

Can PGs aggregate?

Yes

What are interwoven in the basement membrane?

Heparan sulfate (perlecan), collagen, and laminin

Proteoglycans are important in the development of what?

Teeth

In knee cartilage, the proteoglycan acts as what?

Shock absorber

Glycosylation as molecular recognition

1. Assists protein folding in the ER (calnexin, calreticulin, Glc transferase system)

2. Intracellular transport (trafficking to cell surface, mannose-6-P system)

3. Interactions with the immune system

4. Interactions of cells with pathogens (collecting, helicobacter, flu)

5. Cell-cell interactions (white cells/endothelial cells)

The wrong blood transfusion may cause a fatal response to incompatible blood by your ______ system.

Immune

Blood groups A, B, AB, and O depend on what?

Sugar residues at the ends of carbohydrate chains of glycoproteins or glycolipids

Alpha Gal

Galactose 1,3 galactose

Bite of Lone Star tick can cause an allergy to what?

Alpha Gal -- allergic to meat like beef

Transgenic pigs lacking gene to make Alpha Gal can be used for what?

Xenotransplantation

Why are Type O individuals more prone to ulcers?

H. Pylori recognizes specific structures that look like Type O sugars

Linkage difference between Avian influenza virus and Human influenza virus

Avian: α(2-3)

Human: α(2-6)

Selectin-Carbohydrate interactions control _________ trafficking.

Leukocyte

Leukocyte adhesion deficiency II (LAD II) is a defect in what?

Fucosylation

More prone to infection because not enough white cells to fight it

Perlecan is an example of a proteoglycan. What is true about glycosaminoglycans that are found in proteoglycans?

They contain repeating dissacharides

What is the generic name for the domain that binds cell surface galactosyl residues?

Lectin domain