Week 2B: Glycogen metabolism and membrane transporters Flashcards
HC 11-14
Structure free glucose
Contains a very polarized reactive aldehyde group
/H
-C (delta plus) = O (delta minus)
The aldehyde group can react with (in vitro, in vivo, intramolecular)
In vitro: Fehlings reagent (Cu2+ ions)
In vivo: amino groups of proteins
Intramolecular: with the C5 hydroxyl group (count from aldehyde, so opposite one) > form ring
Glucose is a …. sugar
reducing
> can reduce Cu2+ to Cu+ in vitro
> aldehyde group is oxidized to carboxyl group (C(=O)-OH) > gluconic acid
> reducing sugars need free reducing ends
Fehlings test for reducing sugars
Solution of Cu2+ (Fehlings reagent) used in vitro to distinguish reducing and nonreducing sugars.
> glucose and fructose are reducing sugars
> Reducing Cu2+ to Cu+
> 2 Cu+ react with water to form Cu2O (red precipate, red/brown color)
A reducing sugar can reduce a …
another molecule while being oxidized themselves from a sugar with an aldehyde group to a carboxyl group
Two ways of adding glucose to proteins
-Glycosylation: enzymatic transfer of glucose in condensation reaction
-Glycation: nonenzymatic spontaneous and irreversible transfer of glucose
Glycation in vivo
Takes place in vivo between glucose and free amino groups of proteins, such as abundant proteins serum albumin and hemoglobin.
> formation of reversible Schiff base
> conversion to stable ketoamine (irreversible)
Glycation of hemoglobin
-Aldehyde group of glucose reacts with N-terminus of the N-terminal Valine residue of HbA (spontaneous reversible)
> formation Schiff base: C(-H)=N-Val-HbA
> Amadori rearrangement (irreversible, spontaneous)
> HbA1c: C1 of glucose like this: C(=O)-H2C(nr1)-N(H)-Val-HbA
Schiff base bond
-C=N-
How is it possible that the amino terminus of HbA beta chain (tetramer with two alpha and beta chains) is valine and not methionine
Hydrolysis of the N-terminal residue
Glycation of HbA at the..
alpha-amino group of this amino-terminal valine residue of HbA beta chain
> in lesser extent at amino groups at lysine side chains in alpha and beta chains of hemoglobin
Does the glycation of HbA to HbA1c impact the function of hemoglobin
no
The rate of glycation of hemoglobin is proportional to…
blood glucose concentration
Normal HbA1c/HbA% level
5.5%, when hyperglycemia, this can rise
The glycation of stable colagen (ECM protein) increases with …
age
> resembles Maillard reaction in food cooking
The aldehyde group of glucose can react intramolecularly with the c5 hydroxyl group. In which ways
-alpha glucose: c1 hydroxyl group faces away of the oxygen in the chain (36% prevalence)
-beta-glucose: hydroxyl group on C1 faces towards the O (from the C5 hydroxyl group) in the ring
> the cyclic alpha and beta anomers (different conformations of the aldehyde group C1 of glucose)
The conformation of the hydroxyl group on C1 on the cyclic glucose isoforms are called:
Alpha- Axial
Beta- Equatorial, in line with molecule (horizontal)
Glycosylation of glucoses
During enzym-catalyzed reaction, cyclic glucose forms stable covalent glycosidic bond via its C1 anomeric position
Glycosidic bond
reducing end Glucose C1 - O - C4 glucose nonreducing end
After glycosylation, the intrachain glucose cannot ..
adopt an open-chain form anymore
How is a linear homopolymer of glucose residues called?
Glucan
In a glucan, a free reducing end can adopt an open chain formation and keep reducing. In an alpha-1,4-glucan. What is the reducing end?
The end with the free C1 carbon (aldehyde group, reactive)
Initiation formation of proteo-glycogen
Start with glycogenin (GN), the initiator/primer.
> GN is a homodimer and both monomers can glycosylate each other
> each GN monomer is glycosylated specifically on a single tyrosine residue (with the benzene ring with OH group, which forms a bond with the reducing (C1) end of glucose).
> Auto-glycosylation
How long does auto-glycosylation of the GN monomers take place?
Until maximally 8 glucose residues added per glycogenin
> monomers dissociate