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what is the primary responsibility of the liver
maintaining a constant glucose level
how can glucose be produced
gluconeogenesis
glycogen breakdown
Describe lactose
disacc (both sacc. units derived from glucose)
synthesized for later use as a metabolic fuel
produced in mammary gland by lactose synthase (LS)
what are the 2 subunits of LS
galactosyltransferase
α-lactalbumin
describe the galactosyltransferase subunit of LS
catalytic subunit
catalyzes the reaction of UDP-galactose and acetylglucosamine
yields N-acetyllactosamine
- constituent of many complex oligosaccs
describe the α-lactalbumin subunit of LS
mammary gland protein
no catalytic activity
alters specificity of galactosyltransferase
- uses glucose as acceptor
- forms lactose instead of acetyllactosamine
synth. triggered by hormonal changes at parturition
- promotes lactose synth for milk production
Describe lactose intolerance in infants
lactose is hydrolyzed by β-D-galactosidase
- intestinal enzyme
allows for absorption into blood
galactose is enzymatically converted to glucose
Describe lactose intolerance in adult mammals
low levels of β-D-galactosidase
ingested lactose moves to colon
bacterial fermentation generates large quantities of CO2, H2, and irritating organic acids
these result in painful digestive upset
Describe how β-D-galactosidase levels fluctuate by age
β-D-galactosidase levels decrease only mildly with age
What do glycosidic bonds do
link sugars to each other and other molcs.
how much energy is needed to form a glycosidic bond
ΔG° =1 16 kJ/mol
how do glycosidic bonds get their required energy
acquired though synth of nucleotide sugar from monosacc and a nucleoside triphosphate
nucleotide sugar synth -> release of PPi
Describe the glycosylation of proteins
almost all secreted and mem.-associated proteins of euks. are glycosylated
oligosaccs. are covalently attached to proteins by either O- or N- glycosidic bonds
Describe O linked oligosaccs
most common O-glycosidic attachment involves the disascc core β-galactosyl-(1→3)-α-N-acetylgalactosamine linked to the OH of either Ser or Thr
Where does O-linked oligosacc synthesis occur
in golgi apparatus
by serial additions of monosacc units to competed polypeptide
required nucleoside sugars as donors
what are the 2 steps of O-linked oligosacc synthesis
step 1: transfer of N-acetyl-galactosamine (GalNAc)
- from UDP-GalNAc
- to a Ser or Thr residue on the polypep by GalNAc
transferase
Step 2: stepwise addition of sugars
- like galactose, sialic acid, -acetylglucosamine, fructose
Describe N-acetyl-glucosamine (GlcNAc)
invariably β-linked to the amide N from asparagine (Asn) residue
Asn-X-Ser or Asn-X-Thr
-X never pro, rarely Asp, Glu, Leu, or Trp
Describe N-glycosylation
occurs cotranslationally
proteins containing N-linked oligosaccs typically glycosylated then processed
initial glycosylation reaction takes place at ER mem.
what are sugar residues added to in the early stages of N-linked oligosacc synth
sequentially added to the lipid carrier Dolichol pyrophosphate
Describe dolichol and what it does
long chain polyisoprenol containing 17-21 isoprene units
"activates" a sugar residue for subsequent transfer
what is first formed on the dolichol carrier
(N-acetylglucosamine)2 (mannose)9 (glucose)3
12 steps to create this
What is step 1 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
addition of N-acetylglucosamine-1-P and N-acetylglucosamine to dolichol-P
what is step 2 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
addition of 5 mannosyl residues from GDP-mannose
-catalyzed by 5 diff. mannostyltransferases
what is step 3 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
mem. translocation of dolichol-PP-(N-acetylglucosamine)2(mannose)5 to ER lumen
what is step 4 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
cytosolic synth of dolichol-P-mannose from GDP mannose and dolichol-P
what is step 5 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
mem translocation of dolichol-P-mannose to lumen of ER
what is step 6 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
addition of 4 mannosyl residues from dolichol-P-mannose in reaction is
- by 4 diff. mannosyltransferases
what is step 7 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
cytosolic synth of dolichol-P-glucose
what is step 8 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
mem translocation of dolichol-P-glucose
what is step 9 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
addition of 3 glucosyl residues from dolichol-P-glucose
what is step 10 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
transfer of oligosacc from dolichol-PP to the polypep chain of Asn residue
what is step 11 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
translocation of dolichol-PP to cytoplasmic surface of ER mem
what is step 12 of the (N-acetylglucosamine)2(mannose)9(glucose)3 synthesis process
hydrolysis of dolichol-PP to dolichol-P
complete the sentence: One the 14-residue oligosacc is linked to __________ and ___________ starts trimming
Asn glucosidases, mannosidases
(mannose)3(N-acetylglucosamine)2 core is found where
in ALL N-linked oligosaccs