From: winalski@adserv.enet.dec.com (Paul S. Winalski)
Subject: Re: Left-handed sugar
Reply-To: winalski@adserv.enet.dec.com (Paul S. Winalski)
Organization: Digital Equipment Corporation, Nashua NH
Date: Mon, 28 Dec 1992 23:11:01 GMT


In article <dexter.725570507@aries>,
dexter@aries.scs.uiuc.edu (The Gecko) writes:
|>
|>winalski@adserv.enet.dec.com (Paul S. Winalski) writes:
|>
|>>Cells contain a wide variety of enzymes that can convert one isomeric form
|>>of a sugar to another (isomerases), split a sugar into two sugars, or merge two
|>>simple sugars into a longer sugar (transaldolase, transketolase).  The end
|>>result of this is that all of the simple sugars, regardless of isomeric form,
|>>can be converted into D-glucose, the form that is burned in the main catabolic
|>>pathway for sugars to produce energy.
|>
|>>So the L-sugars *are* metabolizable, albeit more slowly than D-glucose, which
|>>is the isomer that most organisms prefer.
|>
|>>So the bottom line is, L-sugars are digestible, albeit not as readily as their
|>>D- counterparts, and they do taste sweet.  On the other hand, disaccharides
|>>with a beta linkage are not digestible, which is why humans cannot survive on
|>>a diet of leaves or wood.  Cellobiose, the beta-1-6-D-glucose disaccharide,
|>>is not digestible, but I don't think it tastes sweet, either.
|>
|>	I don't follow your reasoning here at all.  You have not cited any 
|>example of a D-sugar being converted to an L-sugar, you have only mentioned
|>general examples of sugar metabolism which intercovert *D-sugars*.  By using
|>the term "isomer" loosely, without defining whether you mean an anomer (alpha
|>or beta diastereomer, eg. alpha-D-glucopyranose vs. beta-D-glucopyranose), an
|>epimer (eg. D-glucose vs. D-mannose, or separately, D-glucose vs. L-glucose) 
|>or an enantiomer, you confuse the argument.  Transaldolase and transketolase
|>interconvert *D-sugars*.  Without a further description of which "isomerase"
|>you mean, I can't discuss this issue further, but I would be very surprised
|>to hear of a mammalian (say) enzyme which converted L- to D-sugars.

You're right.  My fundamental mistake was regarding how sugars are classified
L- or D-.  I mistakenly thought that the distinguishing carbon for D-series
vs. L-series sugars was the one right next to the aldo- or keto- carbon, when
in fact it is the asymmetric carbon farthest away from that carbon.  The
isomer interconversion that I was thinking of (via enediols) thus won't touch
the D- or L- configuration.

BTW, I thought "epimer" referred to stereoisomers that differ around the
configuration of one carbon only, in which case D-glucose and L-glucose,
which are mirror images and thus differ at all 4 asymmetric carbons, cannot
be epimers.

|>	Then you have confused digestion and metabolism.  Of course if we are
|>dealing with a free L-sugar then only absorption from the gut needs to occur
|>before metabolism can take place.  But to say an L-sugar is "digestible" at
|>the same time that you affirm cellulose is not "digestible", implies that we 
|>have enzymes to break down glycosidic linkages to L-sugars even though we
|>cannot deal with (many) beta linkages.  To anyone with an idea of enzyme
|>specificity this is absurd.  Why should we have enzymes with the specificity
|>to break down polymers which don't even occur in our diet?

You're right about my confusion of digestion and metabolism in this case.
However, digestive enzymes have a tendency to be relatively non-specific.

|>	Finally, it is beyond me why you *expect* L-sugars to be sweet at
|>the same time that you expect that cellobiose is not.

Cellulose certainly isn't sweet, but I concede your point--cellulose isn't a
disaccharide, either, and polysaccharides such as starches do not taste sweet,
while many disaccharides do.


My biochemistry textbook says nothing about the stereospecificty of the
enzymes involved in sugar metabolism, probably because since in nature, nearly
all sugars are in D- configuration, the subject is relatively moot.  Most of
the action in the enzymes of glycolysis seems to take place around carbon 1,
the exception being the initial phosphorylation of the terminal carbon.  I would
expect that some of the enzymes in glycolysis might be able to act on L-
sugars, albeit at reduced rates, just as some of them can act on epimers and
other analogues of their normal substrates.  Of course, the L-configuration
might end up holding the phosphate at the terminal carbon in such a position
that binding to the enzyme is impossible in most cases.

Have there been any kinetic studies of the glycolytic enzymes with respect to
D-/L- stereospecificty?

--PSW