Section 3: Part 5 - Other Carbohydrate Biosynthetic Pathways

What is the liver's primary responsibility?

maintaining constant glucose levels

What are the 2 ways glucose can be produced?

gluconeogenesis or glycogen breakdown

Where is glucose released from?

liver

glucose can be used by other tissues as an ____________________

energy source

lactose

disaccharide synthesized for later use as a metabolic fuel

Where is lactose produced?

in the mammary gland

What enzyme produces lactose?

lactose synthase

What are the two subunits for lactose synthase?

galactosyltransferase and alpha-lactalbumin

Galactosyltransferase

catalytic subunit

What reaction does Galactosyltransferase catalyze?

UDP-galactose

and acetylglucosamine

What does Galactosyltransferase yield?

N-acetyllactosamine

alpha-lactalbumin

mammary gland protein with no catalytic activity

What does alpha-lactalbumin do?

alters specificity of galactosyltransferase

How does alpha-lactalbumin alter specificity of galactosyltransferase?

uses glucose as an acceptor and forms lactose instead acetyllactosamine

What is alpha-lactalbumin synthesis triggered by?

hormonal changes at parturition (childbirth)

hormonal changes at parturition (childbirth) lead to what?

promotes lactose synthesis for milk production

In infants, what is lactose hydrolyzed by?

beta-D-galactosidase

What does beta-D-galactosidase allow to happen?

absorption into the bloodstream

How is galactose converted to glucose?

enzymatically

lactose intolerance in mammals is due to low levels of what?

beta-D-galactosidase

What happens to lactose when someone is intolerant?

lactose moves to the colon and bacterial fermentation generates gases like CO2, H2, and organic acids

What can CO2, H2, and organic acids lead to?

painful digestive upset

What happens to beta-D-galactosidase levels in populations that have historically relied on dairy products for nutrition throughout life?

levels decrease only mildly with age

glycosidic bonds

link sugars to each other and other molecules

what do glycosidic bonds require?

free energy input

glycosidic bonds gain energy from synthesis of a ________________________

nucleotide sugar

Nucleotide sugar synthesis releases what?

inorganic phosphate

In mammals most glycosyl groups are donated by ___________________

UDP glucose

Almost all secreted and membrane- associated proteins of eukaryotic cells are ___________________

glycosylated

How are oligosaccharide attached to proteins?

covalently attached by either O or N glycosidic bonds

The most common O-glycosidic attachment involves the disaccharide core β-galactosyl-(1→3)- α-N-acetylgalactosamine linked to the _______ group

of either ____ or _____

OH; Ser; Thr

O-Linked Oligosaccharide Synthesis occurs where?

Golgi apparatus

How does O-Linked Oligosaccharide Synthesis happen?

addition of monosaccharide units to completed polypeptide

O-Linked Oligosaccharide Synthesis requires what?

nucleotide sugars as donors

O-Linked Oligosaccharide Synthesis - Step 1

transfer of N-acetyl-galactosamine (GalNAc)

transfer of N-acetyl-galactosamine (GalNAc)

• from UDP-GalNAc

• to a Ser (or Thr) residue on the polypeptide

• by GalNAc transferase

O-Linked Oligosaccharide Synthesis - Step 2

stepwise addition of sugars

N-acetyl-glucosamine (GlcNAc) is invariably -linked to the amide _____________ of an ____________ residue

nitrogen; Asn

Asn-X-Ser or Asn-X-Thr, X cannot be..?

Pro

N-Glycosylation occurs _______________________

cotransitionally

Proteins containing N-linked oligosaccharides typically are ___________________ and then ___________________

glycosylated; processed

Initial glycosylation reactions take place where?

endoplasmic reticulum membrane

Early stages: sugar residues are sequentially added to the ____________________ dolichol pyrophosphate

lipid carrier

Dolichol is a long-chain polyisoprenol containing ___________________ units

17 to 21 isoprene

Similar to nucleoside diphosphate, ________________________ "activates" a sugar

residue for subsequent transfer

dolichol phosphate

N-Linked Oligosaccharide Synthesis is how many steps?

12 step process

N-Linked Oligosaccharide Synthesis - Step 1

Addition of N-acetylglucosamine-1-P and N-acetylglucosamine to dolichol-P

N-Linked Oligosaccharide Synthesis - Step 2

Addition of five mannosyl residues from GDP-mannose

N-Linked Oligosaccharide Synthesis - Step 3

Membrane translocation of dolichol-PP to the lumen of

the ER

N-Linked Oligosaccharide Synthesis - Step 4

Cytosolic synthesis of dolichol-P- mannose from GDP-mannose and dolichol-P

N-Linked Oligosaccharide Synthesis - Step 5

Membrane translocation of dolichol-P-mannose to the lumen of the ER

N-Linked Oligosaccharide Synthesis - Step 6

Addition of four mannosyl residues from dolichol-P-mannose

N-Linked Oligosaccharide Synthesis - Step 7

Cytosolic synthesis of dolichol-P-glucose

N-Linked Oligosaccharide Synthesis - Step 8

Membrane translocation of dolichol-P-glucose

N-Linked Oligosaccharide Synthesis - Step 9

Addition of three glucosyl residues from dolichol-P-glucose

N-Linked Oligosaccharide Synthesis - Step 10

Transfer of the oligosaccharide from dolichol-PP to the polypeptide chain at an Asn residue

N-Linked Oligosaccharide Synthesis - Step 11

Translocation of dolichol-PP to the cytoplasmic surface of the ER membrane

N-Linked Oligosaccharide Synthesis - Step 12

Hydrolysis of dolichol-PP to

dolichol-P

Once 14-residue oligosaccharide is linked to Asn ____________________ and

_________________ start trimming

glucosidases; mannosidases

(Mannose)3(N-acetylglucosamine)2 core found in all _________________________

N-linked oligosaccharides