4. Carbohydrates

Glycosidic Linkages

This lecture doesn’t go into a lot of detail explaining the technicalities of reducing ends, which are critical for understanding the bonding. I added a good description from one of the TA’s on this midway through the notes though.

Overview

To understand the bonding that occurs between two monosaccharides, first review the following reactions:

hemiacetalreactions
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

Recall that glucose has a hemiacetal at its anomeric carbon C1. When this end encounters an alcohol it becomes an acetal.

monosacreaction
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

 More generally, when a monosaccharide bonds with another monosaccharide to form a disaccharide, the hemiacetal (at say, C1) of the first reacts with the alcohol (of the hydroxyl group at C4) on the second to form an acetal. The resulting bond is called a glycosidic linkage.

In the case of Maltose below, it’s called a 1->4 glycosidic linkage corresponding to the carbons being joined.

maltose
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

There are two additional terms introduced in this reaction: that of reducing and non-reducing ends. For Maltose, the non-reducing end is on the left of the first molecule while the reducing end is on the right of the second. A simple way to think about it is this: if there’s a reducing end, the cyclic molecule can return to its linear form. If not, it’s stuck there. When there is a reducing end, the disaccharide is said to be a reducing sugar.

Here’s a great explanation from one of the HarvardX TA’s on how to find reducing ends of these sugars:

A sugar’s reducing end is if/where there is a hemiacetal group. This is almost always the anomeric carbon connected to two oxygens: one is within the (e.g. hexose) ring structure, while the other oxygen is that of the hydroxyl group. The hydroxyl group is the leaving group that gains a hydrogen to form water during the condensation reaction that forms glycosidic linkages.

Sugars have many hydroxyl groups, so the quick way to determine if it is part of a ‘reducing’ end, check if the carbon carrying that hydroxyl group is bonded to a second oxygen. If there is no second oxygen, then the hydroxyl group will not be a good leaving group, so that end of the sugar is not a reducing end.

So, look for an anomeric carbon. If there’s one on the outside, it’s probably a reducing sugar.

Disaccharides are formed any time an anomeric carbon of one sugar (the hemiacetal) reacts with any carbon with a hydroxyl group of another (the alcohol).

This is trehalose, which is a non-reducing sugar since the two reducing carbons (the anomeric carbons) are involved in the linkage. Note that this is a reaction between two identical saccharides. Also note that the glycosidic bond is 1<->1, since it involves both anomeric carbons.

trehalose
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

Similarly, lactose (beta-D-Galactose + beta-D-Glucose) is reducing with a 1->4 glycosidic bond.

And lastly, the famous disaccharide sucrose, which forms by joining an aldose with a ketose, is non-reducing with a 1->2 glycosidic bond. The anomeric carbon of the ketose is C2.

sucrose
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

Glycogen Overview

Complex carbohydrates are made up of more than two saccharides. One of the most important such molecules is glycogen, which is so complex and so large that it can be seen in section of skeletal muscles by electron microscope.

Glycogen is stored in two types of cells: liver cells and muscle cells. It’s an intermediate, short-term energy reservoir.

In the liver, the glucose produced by the hydrolysis of glycogen is exported out of the liver to other tissues that need fuel.

In the muscles, that glucose is used for its own purposes and not exported.

Glycogen Structure

It’s a polymer of alpha-D-Glucose that contains long chains where the glucose units are linked with each other by a 1->4 GL. The structure also includes branches linked by 1->6 GL.

glycogen1
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

For each molecule of glycogen, there’s only one reducing end and many non-reducing ends, since end branch has a non-reducing end.

When energy is needed, the breakdown of glycogen starts by the hydrolysis of the non-reducing ends.

Glycogen Synthesis

When there is a high concentration of glucose in the bloodstream, tissues like liver and muscle will transport glucose into their cells. There, glucose will be converted to G6P via hexokinase (muscle) or glucokinase (liver). Then it’s converted to G1P and from G1P to UDP-Glucose. This is covered in more detail in a later lecture.

glycogen synth

UDP-Glucose will act as a donor of a glucose unit. An enzyme called glycogen synthase (GS) will catalyze the transfer of a glucose from UDP-Glucose to a non-reducing end of an existing glycogen chain, increasing the length of this chain by one unit and the formation of a new non-reducing end (the new glucose).

Branches are formed differently. Creating a branch requires the Glycogen Branching Enzyme. First, the end of a chain is cleaved off create a fragment of ~7 units with a new reducing. That reducing end is connected to an acceptor chain via a 1->6 GL forming the new branch. The glycogen synthase catalyze the elongation of the new branch as well as the acceptor chain that lost its units to create the branch.

Branches occur at ~ every 10 glucose units.
Glycogen contains ~ 55,000 glucose units and 2100 non-reducing ends (at its max)

GS can only operate on chains that are at least four units long. To synthesize a primer chain requires another enzyme called glycogenin, which contains the amino acid Tyrosine. Tyrosine can accept (covalently) a glucose unit donated by UDP-Glucose: the C1 of this glucose unit reacts with hydroxyl group of Tyr residue to form an acetone.

GS will now form a complex with this modified glycogenin. The next three units will still be catalyzed by glycogenin. At the fourth unit, GS takes over to continue the assembly.

glycogenin
from harvardX MCB63X lecture slide, copyright harvardX and edX.org

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