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Lecture 9

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Lecture 9

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  1. 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 • 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