Toews: Glycoproteins/proteoglycans/glycolipids

Front 1

Complex carbs: def

Back 1

COVALENT complexes of sugars and proteins (proteoglycans and glycoproteins) or sugars and lipids (glycolipids)

Front 2

Glycosaminoglycans (GAGs): def

Back 2

Polymers of (-)disaccharide repeat units
ex. Heparin, hyaluronic acid

Front 3

Proteoglycans: def

Back 3

Proteins with lots of GAG chains hooked on
Usually complex with long hyaluronic acid chain (a GAG itself)
Almost all carbohydrate; not much protein

Front 4

Glycoprotein

Back 4

Proteins with some oligosaccharide chains attached
Mostly proteins; not as much CH2O

Front 5

Sulfation

Back 5

Makes OH groups on GAGs even more negative

Front 6

Proteoglycan structure

Back 6

Negative charges repel; "bottle-brush" molecular structure
Monomer = core protein plus lots of charged GAGs
Associates with long hyaluronic acid chain = proteoglycan aggregates

Front 7

Proteoglycan/GAG properties

Back 7

Slippery/slimy- high viscosity; lubricant for mucus, joints
Resilient- low compressibility "shock absorber"; food for synovial fluid in joins and vitreous humor of eye
Around connective tissues, bone matrix, structural integrity

Front 8

Heparin

Back 8

Anti-coagulant GAG
Stored in granules in mast cells that line arterial walls
Released during injury; prevents runaway clotting?

Front 9

Proteoglycan/GAG turnover

Back 9

Endocytosis, vesicle transport to lysosome
Un-degraded GAGs pile up in lysosomes-- debilitating skeletal/structural deformities

Front 10

Glycoproteins: O-linked and N-linked

Back 10

N-terminal AA signal sequence directs to ER/Golgi where sugars added

O-linked: carbs hooked to -OH of Ser/Thr (blood group antigens)

N-linked: carbs hooked onto NH2 of Asn (most glycoproteins; nature of carbs are molecular zip codes)

Front 11

"High mannose" chains

Back 11

Mannose-P targets to lysosomes

Phosphotransferase enzyme and mannose-P receptor involved

Front 12

"Complex" chains

Back 12

Targeted to cell surface or extracellular space

No mannose-P = outside cell

Front 13

Functions of glycoproteins

Back 13

1. CH2O targets glycoproteins to lysosomes or PM (or secreted) - high mannose vs. complex GP
2. Determines half-life of circulating proteins
3. Cell surface recognition
4. Self vs. non-self recognition
5. Blood group antigens
6. Host-pathogen interactions
7. Extracellular matrix and mucins

Front 14

Sphingolipids: def

Back 14

Lots in neurons and myelin

Long-chain amino alcohol (sphingosine) + FA + sugar head

Sphingolipidoses: genetic defects in catabolism --> Mental retardation often present, early death

Front 15

Sphingolipids: functions

Back 15

Structural components of NS membranes

Specialized membrane domains "lipid rafts"

Lipid signaling molecules- 2nd messengers

Ceramide (sphingolipid derivative) can initiate apoptosis

Front 16

Inborn errors of sphingolipid metabolism

Back 16

Genetic mutations in enzymes or activator proteins
Lipid upstream accumulates --> pathology

Depends on:
Localization of accumulating lipid
Prominence of lipid
Turnover rate
Physiological effects of accumulating lipid

Front 17

Krabbe

Back 17

Cerebroside and psychosine build-up

Disruption of metabolic turnover destroys CNS myelin

Psychosine is produced as a result of alternate (abnormal) catabolism; cerebroside is intermediate that builds-up

Front 18

MLD

Back 18

Metachromatic leukodystrophy

Sulfatide build-up

Disruption of metabolic turnover destroys CNS myelin

Front 19

Gangliosides

Back 19

Sialic acid-containing glycolipids
Exclusively on cell surface, especially neurons
Oligosaccharide head is receptor for glycosylated hormones
Determinants of cell-cell recognition, and growth and differentiation

Defective catabolism in Taye-Sachs disease

Front 20

Tay-Sachs Disease

Back 20

Ganglioside build-up in neurons

Cherry red spot on retina is hallmark

Front 21

Blood elements

Back 21

Sphingolipids antigens
A or B
Dominant; antigen will be made if have one copy

Front 22

Sphingomyelin

Back 22

Ceramide-P-Choline
Found in all cells
Lots in myelin
Defect in catabolism in Niemann-Pick A & B

Front 23

Niemann-Pick A & B

Back 23

Build-up of sphingomyelin

Can't catabolize sphingomyelin

Front 24

Degradation of GAGs

Back 24

Lysosomal enzymes (hydrolases) sequentially degrade GAGs

Defects in GAG degradation = mucopolysaccharidoses (un-degraded stuff piles up)

Front 25

Hunter syndrome, Hurler syndrome

Back 25

Defective hydrolases that cleave GAG in lysosome

Mucopolysaccharidoses

Front 26

Protein glycation

Back 26

Non-enzymatic condensation of aldehyde/ketone groups in sugars with amino groups in proteins

Get advanced glycation end-products (AGE)

AGE leads to inflammation, atherosclerosis, diabetic pathology

Depends on concentration of reactants

Front 27

Ceramide

Back 27

Sphingosine + fatty acid

Base of sphingolipids

Front 28

Cerebroside

Back 28

Gal-ceramide

Major myelin lipid

Front 29

Sulfatide

Back 29

Sulfated cerebroside (sulfated gal-ceramide)

Front 30

I-cell disease

Back 30

Extracellular misrouting of acid hydrolases intended for lysosomes