1. Glucose Disposal and Carbohydrate Structure
Lecture 9
Glucose Disposal and Carbohydrate Structure

2. Glycogen Synthase
Catalyses the addition of ‘activated’ glucose onto an existing glycogen molecule
UDP-glucose + glycogenn UDP + glycogenn+1
Regulated by reversible phosphorylation (covalent modification)
Active when dephosphorylated, inactive when phosphorylated
Phosphorylation happens on a serine residue
Dephosphorylation catalysed by phosphatases (specifically protein phosphatase I)
Phosphorylation catalysed by kinases (specifically glycogen synthase kinase)
Insulin stimulates PPI
And so causes GS to be dephosphorylated and active
So insulin effectively stimulates GS

3. Phosphofructokinase
Catalyses the second ‘energy investment’ stage of glycolysis
Fructose 6-phosphate + ATP  fructose 1,6 bisphosphate + ADP
Regulated allosterically
Simulated by concentration changes that reflect a low energy charge
An increase in ADP/AMP and a decrease in ATP
These molecules bind at a site away from the active site – the allosteric binding sites.
Many other molecules affect PFK allosterically but all are effectively indicators of ‘energy charge’

4. Coupling (again!)
The stimulation of glycogen synthesis by insulin creates an ‘energy demand’
Glycogenesis is anabolic
The activation of glucose prior to incorporation into glycogen requires ATP
This drops the cellular [ATP] and increases the [ADP]
This drop in ‘energy charge’ is reflected by a stimulation of PFK
A good example of how an anabolic pathway requires energy from a catabolic pathway
Insulin has ‘indirectly’ stimulated PFK and glucose oxidation even though it does not have any direct lines of communication to this enzyme

5. Carb structure - general
- CHOH- with -C=O ....
makes it a good reducing agent (it, itself can be oxidised)
Aldoses and ketoses
-C=O in aldehyde or ketone position
simplest 3C trioses glyceraldehyde and dihydroxyacetone
no chiral centres in the latter, but one in the former (L & D)
Tetroses (4C) – another chiral carbon appears
Pentoses (5C) pentoses
Can also form ring structure (happens very fast)- -C=0 reacts with one of the far-away CHOHs
creates another stereo-centre
anomeric carbon - alpha or beta - (changing all the time in solution).
Hexoses (6C) - now four chiral centres 24=16 in the aldose
most commonly occurring in nature is the form that has all the -OHs in a plane – D-glucose
Can form a ring in solution – continually opening and closing
Chair and boat configuration

6. More ‘chemistry’ Stereoisomers What you DON’T need to know
molecules with the same formula but different spatial arrangements
What you DON’T need to know
Enantiomers
Stereoisomers that are mirror images of each other
Diastereomers
Stereoisomers that are not mirror images
What you DO need to know…
Epimers - differ in orientation around just one carbon atom.
Glucose and mannose, glucose and galactose.
Anomers – differ in the carbon formed by the ring
Numbering of glucose. May seem pedantic but important when dealing with radioactivity!
Glycosidic Bonds between monosaccharides.
a1-4 and a1-6 glycogen, starch.
b1-4 cellulose
a1-2 sucrose,
b1-4 lactose
No longer reducing sugars when in these bonds.
Ring opening/closing no longer possible

7. Nomenclature

8. Ring Formation
Attack of O on C5 to C1. O on C1 becomes new OH group

9. Haworth Projections
Pyranose ring
Furanose ring

10. Maltose Glycosidic bonds between 1 (alpha anomer) and 4… a14
Still a reducing end (glucose ring on the right can still open)

11. Lactose
Glycosidic bonds between 1 (beta anomer) and 4… b14

12. Sucrose glucose fructose
Glycosidic bonds between 1 (alpha anomer) and 2… a12

13. Glycogen/Starch
Glycosidic bonds between 1 (alpha anomer) and 4… a14 but also a16

14. Cellulose Glycosidic bonds between 1 (beta anomer) and 4… b14
Enables lots of hydrogen bonds between chains and a lattice fibre structure

15. Sugar Tests Free anomeric carbon – a reducing sugar!
transient formation of the aldehyde in solution
Capable of reducing H2O2, ferricyanide, some metal ions (Cu2+, Ag+)
Fehling’s test (Cu) – red ppt
Tollen’s test (Ag) – silver mirror
Most usually done enzymatically and spectrophotometrically
Glucose oxidase – production of H2O2
Colour changes or measured electrochemically
The aldehyde group also makes glucose quite dangerous to have in your body at high concentrations for long periods of time