Glucose Disposal and Carbohydrate Structure Lecture 9 Glucose Disposal and Carbohydrate Structure

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

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’

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

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

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

Nomenclature

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

Haworth Projections Pyranose ring Furanose ring

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

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

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

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

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

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