Glycobiology Flashcards
general formula for carbohydrate polymers
(CH2O)n + P, N, S
define disaccharides and oligosaccharides? how are individual monosaccharides linked together?
Disaccharides = 2 sugars
Oligosaccharides = 2-8 sugars
Linked by O-glycosidic bonds (C-O-C bond)
what is a hemiacetal and why is this important? when does glucose no longer become a hemiacetal?
Hemiacetal = when the anomeric carbon is bonded to an OH and an -O group
(C1 of glucose is hemiacetal)
Being a hemiacetal is important because it allows the ring structure of glucose to open up and become linear.
When the glycosidic bond forms between alpha and beta glucose to form maltose, the end of alpha glucose partaking in glycosidic bond is now an acetal (lost OH group)
This glucose can no longer open up and form a linear structure (locked in its alpha form)
The name of maltose therefore starts with alpha
Beta glucose is still hemiacetal - can open its ring, which also makes it a reducing sugar
Therefore maltose is a reducing sugar
(one note glycobiology 1 for diagrams)
what is an anomer?
what is the anomeric carbon?
Type of stereoisomer that differs in configuration around the anomeric carbon
Anomeric carbon (C-1) = one part of carbonyl (CHO) group in the linear form of glucose
Whether the anomeric carbon is a hemiacetal or not determines the reducing ability.
(alpha and beta glucose are anomers - they are also stereoisomers)
what is the systematic name of maltose and lactose.
Explain the namings
maltose = α-D-glucopyranosyl-(1->4)-D-glucopyranose
lactose = β-galactosyl-(1->4)-glucose
Both maltose and lactose are reducing
The galactose (left) joins in its beta form, and the glucose on right is still hemiacetal, so can open its ring structure (reducing)
NOTE - pyranosyl means 6 membered ring
what is the systematic name of sucrose? is it reducing? why/why not?
Sucrose = α-glucosyl-(1->2)-fructose
NON reducing
The anomeric carbons of both glucose (C1) and fructose (C2) are locked in with glycosidic bonds
No hemiacetals - cannot open up its ring structure so not reducing
what are oligosaccharides and polysaccharides?
abundance?
2-8 linked monosaccharides
Low abundance in nature, mainly in plants
Polysaccharides = more than 8 monosaccharides
High abundance in nature, split into storage and structure
2 main examples of structural polysaccharides?
cellulose: homopolymer of glucose units (beta 1,4 linked) and unbranched
Chitin: homopolymer of N-acetylglucosamine (beta 1,4 linked) and unbranched
storage polysaccharides - starch and glycogen
Can they be reduced?
Starch = mixture of 2 polymers
Alpha amylose - unbranched glucose polymer, alpha 1,4 linked
Amylopectin - alpha(1,6) linked branches every 24-30 glucose
Glycogen - similar to starch but more branched
May have a reducing end, but their capacity to be reduced is very small compared to their size
what are glycosaminoglycans? how long? what are they the major component of?
a range of polymers composed of repeating disaccharide units
Several 100s of units long
component of ground substance
what is ground susbtance?
Material found in all animals
- between cells - allow molecule movement between cells
- hold cells together/ cell-cell contact
-made up mainly of glycosaminoglycans
example of glycosaminoglycans?
hyaluronic acid (in ground substance, synovial fluid and vitreous humour of the eye - allow light to pass through lens)
viscous, absorbs shock and shearing forces
250- 25,000 repeating disaccharides of D-glucuronic acid that is beta 1,3 linked to N-acetyl-d-glucosamine
disaccharides are attached to each other with beta 1,4 linkages
Combination of beta 1,3 and beta 1,4 alternating linkages along the chain
1,4 gives structure
1,3 provides movement
why does structure of glycoproteins vary?
Carbohydrate added is not coded for (like proteins)
Type/number of sugars added depends on availability of enzyme at that point in time (e.g. diff blood groups due to diff presence of enzymes)
Results in microheterogeneity - CH content varies
N-linked glycoproteins
CH N-acetylglucosamine (NAG) is beta linked to the amide nitrogen of Asn in protein seq:
Asn-X-Ser OR Asn-X-Thr
X is any AA except proline
Complex sugars with this NAG base added to proteins in ER
O-linked glycoglycoproteins
Attachment of carbohydrate to OH group of Ser or Thr (sometimes hydroxylysine)
Broader range of possibilities than N-linked - single galactose to 1000 disaccharide units
ABO blood groups - determined by O-linked sugars
glycogen structure (bonds, any proteins)
glycogenin (protein component) - homodimer
B chains (inner component) - 2 branch points
A chains (outer) - not branched = 34.6% of molecule (easily broken down by enzymes)
how many glucose residues in vivo glycogen molecule? how and why does this differ from the theoretical maximum
in vivo molecule = 1500 glucose residues
theoretical =55,000
This does not occur due to steric hindrances, which prevents enzymes reaching all the glucose residues
structural diversity of glycogen
polydisperse - variable structure between molecules
uneven shapes of molecules - glycogenin is not always in the centre
diff residue number in each molecule
glycogenin
protein component of glycogen
has a single chain attached to it, that is alpha 1,4 linked
all other chains branch from this single chain
how does glycogen grow
-13 residues are added by glycogen synthase
-the branching enzyme amylo(1,4 -> 1,6 transglycosylase) breaks 1,4 bond and transfers end chain (around 7R) toC6-OH lower down chain by alpha 1,6 bond (creates branch)
how are the first 10-20 glucose residues added
glycogenin catalyses the addition of the first glucose to Tyr-195
around 10-20 residues are added to this chain
glycogen synthase takes over
how d
o glycogenin and glucose synthase add glucose molecules
use activated precursor molecules
in eukaryotes = UDP-glucose (acts as glucose donor)
UTP + G1P <=> UDP-glucose = PPi
catalysed by UDP-glucose pyrophosphorylase
Terminal 2 phosphates of UTP form PPi
PPi cleaved into 2 phosphates to prevent reverse reaction
what is mechanism of UDP-glucose formation
Exact mechanism is unknown
Not SN2 (nucleophillic substitution) as only alpha glucose is produced
if SN2, the carbocation would flip on reaction completion to give mixture of alpha and beta glucose
perhaps a variant of SNi?
3 enzymes involved in degredation of glycogen
is degredation a reversal of synthesis?
glycogen phosphorylase
glycogen debranching enzyme
phosphoglucomutase
No degredation is not a reversal - distinctly different
this enables the regulation of both at the same time
glycogen phosphorylase
- what does it do?
- what does it use?
- mechanism?
- aided by?
breaks 1,4 linkages within 5 residues of branch point (too big so cannot reach further)
uses phosphate - forms alpha G1P
mechanism = nucleophillic sub via carbocation (SN1)
carbocation is stabilised by pyridoxal phosphate (PLP) - covalently linked to enzyne
PLP is active form of Vit B6
glycogen degredation -glycogen debranching enzyme
(note before this - glycogen phopshorylase has removed all residues in the branch within 5, so theres 4 left)
bifunctional
1. transferase
breaks alpha 1,4 linkage - snips 3R from branch and transfers to the end of the chain (leaves 1 glucose)
2. alpha 1,6 glucosidase
removes remaining 1 branched glucose by breaking alpha 1,6 bond
glycogen degredation - phosphoglucomutase
how does it work?
converts G1P <=> G6P
G6P can enter glycoglysis (bypass first step), or enter liver where they are dephosphorylated to form glucose
- phosphate bound to enzyme at serine residue (has OH to allow for formation of phosphodiester bond)
- attaches at C6 (form G1,6P)
- phosphate at C1 is transferred to the enzyme
how is synthesis and breakdown of glycogen regulated when glucose is plentiful?
G6P formed by hexokinase
this shifts eqm to left (phosphoglucomutase converts G6P to G1P, the reverse reaction)
G1P is the substrate to form UDP-glucose
UDP-glucose used to synthesise glycogen
therefore, phosphoglucomutase can regulate synthesis as well as breakdown
how do synthesis and breakdown rates of glycogen compare in muscle and liver
muscle - breakdown occurs 300x faster than synthesis
Required to rapidly release glucose, replenishment of glycogen does not need to occur too quickly
liver - synthesis and breakdown rates are equal
(maintain blood glucose)
