Structural Biochemistry/Carbohydrates/Ketoses

A ketose is a ketone with two or more hydroxyl groups (-OH), where at least one of the hydroxyl group at each end. Ketoses are a type of monosaccharide, which are important fuel molecules and nucleic acid building blocks. The simplest example of a ketose is dihydroxyacetone. It is a three-carbon structure containing one keto group and two hydroxyl groups (shown below). If you look closely at the image below you will notice that the keto group is in a slightly different color. The formula for this structure is CO(CH₂OH)₂. Ketoses also play important roles in the Calvin cycle, transaldolase reaction and transketolase reaction. Each of these processes are described in the following sections below.

The simplest ketose is Dihydroxyacetone. The stereochemical relations between D-ketoses containing three-four, five, and six carbon atoms are shown below in the family tree of ketoses:

Furanose Formation

Hemiketal or Hemiacetal

A Hemiketal is formed when a ketone react with an alcohol. The ‘-OR’ in alcohol attacks the oxygen in ketone, thus breaking the ‘C-O’ double bond. And the ‘H’ in alcohol bonds to the O.

Hemiketal Formation

Furanose Ring

Fructose chain cyclize when the -OH on C5 attacks ketone on C2 to form intramolecular hemiketal. It can form both 5 membered furanose ring or 6 membered pyranose ring. the Furanose ring makes the envelope ring form, with either C2 or C3 out of the plane; these are called C-2-endo and C-3-endo.

Ketoses in Reactions

Transketolase Reaction

The Transketolase reaction is very similar to the Transaldolase reaction. However, the Transketolase is different because it transfers a two carbon unit instead of Transaldolase's three carbon unit. Thiamine pyrophospate (TPP) ionizes so that it has a carbanion which is a negatively charged carbon. The importance of carbanion is that they can attack carbonyls, so that carbons are added in a sense to the nucleophile. TPP attacks a ketose substrate where it than releases the aldose product to yield an activated glycoaldehyde unit. An activated glycoaldehyde unit is an electron sink because of a positively charged nitrogen atom where a carbonyl of an aldose product is attacked and then separated after some electron movement. The importance of the transketolase reaction is that it is the mechanism that the enzyme TPP uses to change a ketose substrate to a ketose product that has a different group attached to it.

Transaldolase Reaction

The transaldolase reaction involves the transfer or a three carbon dihydroxyacetone unit from a ketose donor to an aldose acceptor. Unlike the transketolase reaction, transaldolase does not contain a prosthetic group; instead the reactions begins with a Schiff base formed between the carbonyl group of the ketose substrate and the amino group of a lysine residue at the active site of the enzyme. Next the Schiff base is protonated and the bond between C-3 and C-4 break which releases the aldose product. The leftover negative charge on the Schiff-base carbanion is stabilized by resonance while the positive charge on the nitrogen atom of the protonated Schiff base acts as the electron sink. The Schiff-base remains stable until a suitable aldose becomes bound which allows the dihydroxyacetone to react with the carbonyl group of the aldose and the ketose product is released from the lysine side chain via hydrolysis of the Schiff-base.

Transaldolase is a target of autoimmunity in patients with multiple sclerosis which is the selective destruction of oligodendrocytes that selectively expresses transaldolase in the brain.

Ketose in the Calvin Cycle

The Calvin cycle, or dark reactions, is one of the light-independent reactions. In the third phase of the this reaction, a five-carbon sugar is constructed from six-carbon and three-carbon sugars. A transketolase and an aldolase are the major factors in the rearrangement. The transketolase, which is in the pentose phosphate pathway, requires a coenzyme, thiamine pyrophosphate (TPP), to transfer a two-carbon unit from a ketose to an aldose. Whereas the transaldolase transfers a three-carbon unit from a ketose to an aldose.

In summary, transketolase first converts a six-carbon sugar and a three-carbon sugar into a four-carbon sugar and a five-carbon sugar. Then, aldolase combines the four-carbon product and a three-carbon sugar to form the seven-carbon sugar. This seven-carbon sugar then finally reacts with another three-carbon sugar to form two additional five-carbon sugars.

References

Berg, Jeremy, John Tyzmozcko, Lubert Stryer. Biochemistry

Berg, Jeremy, John Tyzmozcko, Lubert Stryer. Biochemistry Sixth Edition page 306