Fructose, Lactose, Glycoproteins, Proteoglycans, and GAGs

What two monosaccharides make up sucrose?

fructose and glucose

Fructose catabolism feeds into...

glycolysis and fatty acid synthesis

Which enzyme breaks down sucrose into glucose and fructose?

sucrase

What happens during step 1 of sugar metabolism?

phosphorylation

Hexokinase has a _______ affinity for fructose

low

Hexokinase only catalyzes fructose phosphorylation in _____ glucose and _____ fructose environments

low; high

What is a better enzyme for fructose phosphorylation compared to hexokinase?

fructokinase

Fructokinase is more commonly used in _____ glucose and _____ fructose environments

high; high

Fructose 1-P is used in...

glycolysis and triacylglycerol synthesis

What happens during step 2 of fructose metabolism?

cleavage of fructose 1-P into trioses for entry into glycolysis and other pathways

What is the key enzyme used for cleavage into trioses?

aldolase B

What does aldolase B do?

cleaves fructose 1-P into DHAP and glyceraldehyde

Aldolase A and C can cleave ________, but not ________

Fructose 1,6-bisphosphate; fructose 1-P

Which triose feeds into glycolysis?

DHAP

Which triose is part of the glycerol synthesis pathway?

glyceraldehyde

What is essential fructosuria?

a rare, but benign, condition that occurs when people don't like to consume sugar very much

Essential fructosuria causes...

fructokinase deficiency

What happens during essential fructosuria?

fructose is not converted into fructose 1-P

What is Hereditary Fructose Intolerance?

aldolase B deficiency that results in a fatal condition

HFI occurs 1 in every ________ births

20,000

What is lactose?

the disaccharide of galactose and glucose

Lactase deficiency causes...

lactose intolerance

What happens during lactose intolerance?

bacteria metabolize lactose to acids and CO2, causing bloating, diarrhea, and dehydration

What is the 1st step of galactose metabolism?

phosphorylation of galactose by galactokinase

What is the 2nd step of galactose metabolism?

galactose 1-P changes into glucose 1-P

Which enzyme converts galactose 1-P into glucose 1-P?

galactose 1-phosphate uridylyltransferase (GALT)

Glucose 1-P feeds into _________, which is then...

glycogen pathways; connected to other pathways like glycolysis, GNG, and PPP

What happens during classic galactosemia?

no GALT

How do you treat galactokinase deficiency and classic galactosemia?

removal of galactose (lactose) from diet

Elevated levels of galactose drive abnormal side pathways to...

galactitol

Which enzyme converts galactose to galactitol?

aldose reductase

Increased galactitol causes...

cataracts

True or False: sugars only provide energy

False

What other functions do sugars have other than providing energy?

- cell structure and identity

- VIP post-translational protein modifications

The outside of most cells is coated in a...

glycocalyx

Sugars are found on the _________ of membranes

outside

Most, if not all, surface and secreted proteins are...

post-translationally glycosylated

Which surface/secreted proteins are glycosylated?

- cell suface proteins (plasma membrane transporters such as GLUTs)

- extracellular matrix proteins (collagen)

- peptide hormones (insulin)

- antibodies

- secreted proteins (salivary enzymes)

- mucins (lubricants)

Membranes or extracellular proteins are nonfunctionall UNLESS...

they are fully glycosylated

All cells sit on or nestle in an _______________ composed of...

ECM; glycosylated proteins and other carbohydrate-rich molecules

Epithelial cells sit on a...

basal lamina/basement membrane

What are the glycoprotein components of the basal lamina?

laminin and type IV collagen

Epithelial cells always form...

selectively permeable barriers

________________ nestle in an ECM

mesenchymal cells

What are the proteoglycans/GAGs of the ECM?

hyalyronan and aggrecan

Collagen and other ECM components work together to provide what functions?

composition and hydration control

Which glycoproteins are found in the ECM?

laminin, nidogen, and fibronectin

Teeth and bone are composed of a...

mineralized ECM

Joints are normally cushioned by...

hydrated proteoglycans

What takes up a large amount of space by holding a lot of water in synovial fluid?

hyaluronan

The ECM of joints contains...

one globular protein

one glycogen

one collagen

one hydrated molecule of hyaluronan

Which ECM component allows the fluid to have a cushioning activity

hyalyronan

What happens during osteoarthritis?

thinned cartilage, resulting in no cushion

What are glucosaminoglycans (GAGs)?

disaccharides of an acidic sugar and an amino sugar

Disaccharides of GAGs repeat up to...

25,000 times

What does the acidic sugar of a GAG have?

carboxylic acid

What does the amino sugar of a GAG have?

an amino group

What are the notable monosaccharides in GAGs, which occur with or without sulfates? (MUST KNOW)

- glucosamine

- N-acetylglucosamine

- galactose

- N-acetylgalactosamine

- glucuronic acid

- iduronic acid

GAGs are ________ attached to a _________ in the form of _________, EXCEPT _________

covalently; core protein; proteoglycans; hyalyronan

What are the names of notable GAG classes?

- chondroitin sulfates

- keratan sulfates

- hyaluronic acid

- dermatan sulfate

- heparin

- heparan sulfate

Which GAG has the primary role of cushioning joints and ocular fluids?

hyaluronic acid

Which GAG has the primary role of providing structure to cartilage, tendons, bone, skin, valves, vasculature, and cornea?

- chondroitin sulfates

- dermatan sulfate

- keratan sulfate

Which GAG has the primary role of being a ubiquitous component of cell surfaces and basement membranes?

heparan sulfate

Which GAG has the primary role of being an anti-coagulant?

heparin

GAGs are mostly __________ with a _________

amino- or acid-sugar polymers; tiny peptide portion (this is why they are considered proteoglycans, not glycoproteins)

Glycoproteins are...

proteins decorated with oligosaccharides

Proteoglycans are...

glycans coated with proteins

In the ER, oligosaccharides are mostly attached to...

asparagine (N-linked)

In the Golgi, oligosaccharides are attached to...

serine and threonine (O-linked)

Initial modification of peptides occurs in the ______, while more modification occurs in the _______

ER; Golgi

GAGs are degraded in ___________ by __________ that function best at ________ pH

lysosomes; hydrolases; acidic

Acid hydrolases only work in...

acidic environments

Acid hydrolases that leak out won't work well in...

the cytoplasm which have a neutral pH

Lysosomes have a pH of...

<5

What are mucopolysaccharidoses?

a subset of lysosomal storage diseases

Severity of mucopolysaccharidoses varies by...

enzyme

mucopolysaccharidoses are caused by...

defects in GAG-degrading lysosomeal hydrolases

The most sever form of mucopolysaccharidoses are...

I-cell diseases

What are I-cell diseases?

when lysosomes lack nearly all acid hydrolases

Children with mucopolysaccharidoses initially develop _______ followed by a...

normally; decline in physical and/or mental function

What therapies are currently under investigation to treat mucopolysaccharidoses?

enzyme replacement and stem cell therapies

____________ occur in some mucopolysaccharidoses

oral anamolies

Which of these ingredients is most likely to ameliorate arthritis symptoms?:

Calcium

Cellulose

Chondroitin

Glucosamine

Ferrous sulfate

Chondroitin and Glucosamine

If mis-localized to the neutral pH cytoplasm, which of these AAs are most likely to disrupt acid hydrolase conformation and thus function?

Arginine

Cysteine

Histidine

Leucine

Valine

Histidine

Infants w/ fructose intolerance can react severely after weaning. Lethargy, seizures, and coma may occur if large quantities of sugar are ingested. Persistent intake can lead to chronic toxicity, including liver and kidney damage. Those who survive the early period w/o correct diagnosis develop a self-protective aversion to harmful sugars. Which enzyme is likely involved?

Aldolase B

Which of these monosaccharides is not a GAG component?:

Fructose

Glucosamine

Galactose

Glucuronic acid

N-acetyl glucosamine

N-acetyl galactoasmine

Iduronic acid

Fructose