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A primer on simple and complex carbohydrate
and glycolipid structure,
nomenclature, and function (I DONT KNOW)
nomenclature, and function (I DONT KNOW)
This
Get Up To Speed (GUTS) session covers
some very basic concepts of carbohydrates and glycolipids
– their structure, nomenclature, properties, and general functions. Lipid structure and nomenclature were covered
in an earlier GUTS session, but glycolipid structures and nomenclature are
described in more detail in this session.
Begin
by taking the self-assessment exam starting on the next page. If you get most all of them right, you’ll
most likely do fine with the related material in your Molecules to Cells block. If you miss several questions, or if you’d
just like to know more about the subjects (never a bad idea), do one or all of
the following:
a) read the materials outlined on the pages that
follow and retake the exam.
b) look at and listen to the taped GUTS lecture,
then retake the exam
c) read any suitable textbook of biochemistry and
retake the exam.
There is no required textbook for the “Molecules to Cells”
block of instruction.
However, if you’re looking for an inexpensive optional companion to the
biochemistry portions of Molecules to Cells, you might consider “Lippincott’s
Illustrated Review: Biochemistry,” 3rd ed, by Champe, Harvey, and
Ferrier. It has a condensed text, nice
figures and diagrams, and isn’t very thick or heavy.
There
are a number of good rather detailed textbooks on biochemistry, NOT worth buying if you don’t already own a
copy. These include, but are not limited
to:
Biochemistry
(Berg, Tymoczko, & Stryer), 6th ed, 2007
Lehninger
Principles of Biochemistry (Nelson & Cox), 4th ed, 2005
Fundamentals
of Biochemistry (Voet, Voet, & Pratt), 2001
Biochemistry
(Garrett & Grisham), 3rd ed, 2005
Contact Information:
SELF-ASSESSMENT EXAM FOR CARBOHYDRATES AND
GLYOLIPIDS
1. In carbohydrates, the average C-atom is at
the oxidation level of a(n):
a)
saturated hydrocarbon chain
b) alcohol
c) aldehyde or ketone
d) carboxylic acid
e) carbon dioxide
b) alcohol
c) aldehyde or ketone
d) carboxylic acid
e) carbon dioxide
2. An alcohol is more / less reduced
than a carboxylic acid, while carbon dioxide is
more / less oxidized than a saturated hydrocarbon chain.
more / less oxidized than a saturated hydrocarbon chain.
Match
the best answer below to each of the following five statements. You may use each answer more than once.
a) glucose
3. 5-C sugar that is a component
of RNA
b) sucrose
c) starch 4. fruit sugar; disaccharide consisting of glucose and fructose
d) glycogen
e) cellulose 5. storage form of glucose in plants
f) fructose
g) lactose 6. milk sugar; disaccharide made of glucose and galactose
h) ribose
i) hyaluronic acid 7. monosaccharide at the center of energy metabolism
b) sucrose
c) starch 4. fruit sugar; disaccharide consisting of glucose and fructose
d) glycogen
e) cellulose 5. storage form of glucose in plants
f) fructose
g) lactose 6. milk sugar; disaccharide made of glucose and galactose
h) ribose
i) hyaluronic acid 7. monosaccharide at the center of energy metabolism
8. Med students and other mammals store glucose
as:
a)
amylose
b) amylopectin
c) starch
d) glycogen
e) cellulose
b) amylopectin
c) starch
d) glycogen
e) cellulose
9. Glycosaminoglycans (GAGs) are:
a)
glycoproteins
b) nucleic acids
c) long, linear charged polysaccharides with disaccharide repeat units
d) branched-chain polymers of glucose and galactose
e) principal components of chitinous exoskeletons of grasshoppers and blue crabs
b) nucleic acids
c) long, linear charged polysaccharides with disaccharide repeat units
d) branched-chain polymers of glucose and galactose
e) principal components of chitinous exoskeletons of grasshoppers and blue crabs
10. Glycosaminoglycans (GAGs) are involved in:
a) compaction
of DNA into nucleosomes
b) energy storage in liver and adipose tissue
c) formation of extracellular matrix, mucus, and synovial fluid in joints
d) signal transduction pathways
e) transfer of fatty acids into mitochondria for oxidation
b) energy storage in liver and adipose tissue
c) formation of extracellular matrix, mucus, and synovial fluid in joints
d) signal transduction pathways
e) transfer of fatty acids into mitochondria for oxidation
11. Which of the following is common to all
sphingolipids?
a) ceramide
(sphingosine + fatty acid)
b) glycerol
c) phosphate group
d) sterol nucleus
e) oligosaccharide chains
b) glycerol
c) phosphate group
d) sterol nucleus
e) oligosaccharide chains
12. Like phospholipids, sphingolipids are
amphipathic molecules present in cell membranes. This statement is:
True
False
False
Match
the sphingolipid below to the statement that best describes it. You may use each answer more than once.
a) sphingosine 13. major
component of the myelin sheath
b) cerebroside
c) gangliosides 14. preferentially localized in neuronal cell membranes
d) globosides
e) sphingomyelin 15. a sphingolipid that’s also a phospholipid
f) ceramide
b) cerebroside
c) gangliosides 14. preferentially localized in neuronal cell membranes
d) globosides
e) sphingomyelin 15. a sphingolipid that’s also a phospholipid
f) ceramide
INTRODUCTION
Carbohydrates
are the most abundant organic molecules on the earth. They have the general empirical formula (CH2O)n,
and so are chemically “hydrates of carbon”
– hence their name. The average C atom
of carbohydrates is at the alcohol (R-OH) level of oxidation, relatively reduced and relatively energy-rich.
Fats, by the way, are even more
reduced (and more energy-rich, basically at the level of a saturated
hydrocarbon chain). Carbon dioxide, CO2 (O=C=O) is as
oxidized (and as energy-poor) as C atoms get.
Functions of carbohydrates include serving as energy sources (dietary
carbohydrates) and as energy stores (glycogen
in liver and muscle; starches in plants).
As part of glycoproteins and glycolipids, they serve as cell membrane components that are involved in cell-cell interactions and various forms of intercellular communication. As part of mucopolysaccharides
and glycosaminoglycans, they are also
important components of the extracellular matrix. Although not in med students or other mammals,
carbohydrates also serve as structural components – cellulose in plants, cell
walls of bacteria, and the chitinous exoskeleton of crustaceans and
insects.
STRUCTURE AND NOMENCLATURE OF CARBOHYDRATES
Sugars
(carbohydrates) are chemically polyalcohols
(several – OH groups) that also contain a carbonyl (C=O) group; the latter is
either an aldehyde or ketone.
The simplest aldose is
glyceraldehyde and the simplest ketose
is dihydroxyacetone (see figure).
Phosphorylated derivatives of these two molecules are important
intermediates in glycolysis, which lies at the heart of energy metabolism.
Glucose
is perhaps the most common simple sugar – it has 6 carbons (hexose) and is an
aldose. The structure is shown on the
next page. Hexoses (and pentoses like
ribose) like to form rings in solution, and they are usually shown in this manner. We even get tired of drawing correct rings,
and so have developed a short-hand method for depicting the various
sugars. Look over the diagrams below and
be sure you understand the basic structure of glucose (when the ring closes,
the C1 –OH can either be below (a-configuration) or above (b-configuration) the plane
of the ring – there is rapid equilibrium between these two forms and the open
chain form. There are also several isomers of glucose (same chemical formula,
different molecular configuration) that are common in metabolism, galactose and mannose
being the most prominent. They differ
from glucose in having some of their –OH groups on the other side of the C-C
chain (or up/down in the ring structures).
The configuration of –OH groups above or below the plane of the sugar rings may
seem like a minor thing, but in their configuration lies great specificity with
respect to carbohydrate chains on membrane glycolipids and glycoproteins, and
these chains form the basis for cell-cell recognition and other complex
cell-cell interactions. All of the
antigenic determinants (self vs non-self – lots more about this in Block 4 - Immunology)
are specific complex carbohydrate moieties as well.
 |
| FOOD AS THE SOURCES OF CARBOHYDRATE |
Fructose is another important sugar – it is a
ketose and also likes to form a ring in solution.
Ribose
and its derivative, 2-deoxyribose, are
components of nucleotides that are the building blocks for RNA (ribose is the R in RNA) and DNA (deoxyribose is the D in DNA). Ribonucleotides are also big players in cellular
metabolism (ATP = energy carrier; GTP = G-protein signaling; UTP = complex carbohydrate synthesis; CTP = complex lipid synthesis).
There are also derivatives of simple sugars and some examples
are shown in the diagrams below. You
don’t need to know the structures of these molecules, but note that their
modifications can have important consequences in terms of their biological
functions. For example, acidic sugars carry (-) charges at
physiological pH, so polymers of these sugars repel each other; amino sugars like
glucosamine have a (+) charge, but their acetylated derivatives (e.g., N-acetylglucosamine) do not.
Simple sugars are often linked
together by glycosidic links – a
dehydration or condensation reaction.
Hydrolysis (addition of water across a bond) of glycosidic links regenerates
the sugar monomers. Simple sugars are
called monosaccharides, two joined
sugars are disaccharides, several joined
sugars (3-20 or so) are oligosaccharides,
and sugar polymers (dozens to thousands of monomers) are called polysaccharides.
Maltose (malted grains; 2 glucose monomers), sucrose (fruit sugar; glucose and fructose) and lactose (milk sugar; glucose and galactose) are
good examples of disaccharides.
Remember that the ring structures of
sugars are constantly opening and closing, with the –OH of C1 being either
below or above the plane of the ring (a or b
configurations, respectively). However,
when C1 of a sugar participates in a glycosidic link, the configuration is
locked into either the (a or b configuration.
This has important implications for overall structure/function and
enzyme specificity (read on).
Polysaccharides: Glucose polymers are important carbohydrate
storage forms in plants (starches) and animals (glycogen in liver and muscle). Starch
is composed of amylose (long linear
chains of glucose in a1®4 links) and amylopectin
(long linear chains of glucose in a1®4
links with a1®6
links at the branch points). Glycogen has a branched-chain structure similar
to amylopectin, and each glycogen molecule can have over 500,000 glucose
units. Cellulose
has a structure similar to amylose, except it has b1®4 links instead of a1®4
links. The long strands of b1®4
links tend to form sheets of high tensile strength and provide structure for
plants. We (enzymes in our gut) can
easily digest the a1®4
links between glucose monomers in plant starches and glycogen, but don’t have
enzymes to digest the b1®4 links in cellulose.
Bacteria that live in the stomachs of ruminants (sheep, cows, giraffes)
and protozoa that live inside termites can though, allowing those creatures to
happily exist on hay and straw, and on houses and rain forests,
respectively.
Glycosaminoglycans (GAGs): Not all sugar polymers are made exclusively
of glucose. Glycosaminoglycans
(sometimes called mucopolysaccharides)
are long unbranched heteropolysaccharide chains, usually composed of a repeating disaccharide unit consisting of an
acidic sugar
(- charge) and an amino sugar (but with the amino group acetylated, so no + charge). Many are sulfated, so they have even more negative charges. All those negative charges repel each other, so the chains are extended and “slippery.” GAGs make up the extracellular matrix, especially important in connective tissues like cartilage, tendon, skin, and blood vessels. They are also important components of mucus (lubrication) and synovial fluid of joints and the vitreous humor of the eye (shock-absorbers). Examples include hyaluronic acid, chondroitin sulfates, heparan sulfate and
(- charge) and an amino sugar (but with the amino group acetylated, so no + charge). Many are sulfated, so they have even more negative charges. All those negative charges repel each other, so the chains are extended and “slippery.” GAGs make up the extracellular matrix, especially important in connective tissues like cartilage, tendon, skin, and blood vessels. They are also important components of mucus (lubrication) and synovial fluid of joints and the vitreous humor of the eye (shock-absorbers). Examples include hyaluronic acid, chondroitin sulfates, heparan sulfate and
heparin.
Unlike other GAGs, which have extracellular structural functions,
heparin functions as an anticoagulant. Proteoglycans
are proteins with lots of GAG chains attached to them. They, in turn, are usually complexed with a
long hyaluronic acid chain, itself a GAG,
to form proteoglycan aggregates. We will cover these in more detail in the
Glycoproteins, Proteoglycans, and Glycolipids lecture on Aug 20.
There are a number of
clinically significant hereditary disorders of glycosaminoglycan metabolism,
generally classified as mucopolysaccharidoses. There is accumulation
of undegraded GAGS in various tissues, resulting in skeletal and
other structural deformities as well as mental retardation. The underlying metabolic deficit is usually
incomplete GAG degradation in lysosomes.
Finally, a little on sphingolipid structure and nomenclature. This section is relevant to the upcoming
Glycoproteins, Proteoglycans, and Glycolipids lecture on Aug. 20, and to the
Case Conference on Aug. 23. Most (but
not all) glycolipids are sphingolipids (and thus glycosphingolipids), but there
are also some sphingolipids that are not glycosphingolipids. The following section is intended to try to
make some sense out of the above admittedly confusing situation (which is not
my fault, by the way).
The basic structure of sphingolipids is shown in the figure below (review
the Lipids GUTS material if you need). Like phospholipids, sphingolipids are
amphipathic (both hydrophobic and hydrophilic properties) and they are
important components of cell membranes, particularly in the nervous
system. Sphingolipids
consist of the long chain amino alcohol sphingosine,
which usually has a long-chain fatty acid linked
by an amide bond. The sphingosine-fatty
acid moiety is called ceramide. Various groups (usually but not always 1 or
more sugars) are attached to the –OH of ceramide – as shown in the figure on
the next page.
Sphingomyelin
has a phosphoryl-choline group attached to ceramide; it is thus both a
sphingolipid and a phospholipid (but not a glycerophospholipid like PC, and
also not a glycosphingolipid). Ceramide and sphingosine
derived from sphingomyelin catabolism play roles in intracellular
signaling.
Cerebroside
is galactose-ceramide, and its sulfated
derivative is called sulfatide – both
are important myelin lipids.
Glucosyl-ceramide is the precursor for other more
complex glycosphingolipids, including the globosides
and gangliosides. Gangliosides
are especially prominent in neuronal membranes. Both gangliosides and globosides have a
number of sugar residues attached.
Glycosphingolipids
are localized in the outer leaflet of the plasma membrane of all
cells, where they help regulate cell-cell
interactions, growth, and development. The carbohydrate
chains of glycosphingo-lipids are antigenic
(e.g., ABO
blood group antigens). They
also serve as cell-surface receptors for
tetanus and cholera
toxins (the latter interferes with
G-protein signaling cascades – more on this soon in your upcoming
hormone/signal transduction lectures).
There are a number of inborn errors of sphingolipid metabolism, generally
called sphingolipidoses - although individually rare, they are
collectively a clinical concern in pediatrics.
That’s one reason it’s good to have a general understanding of their
structure, nomenclature, and functions.
ANSWERS TO SELF-ASSESSMENT EXAM
1. b 9. c
2. more, more 10. c
3. h 11. a
4. b 12. True
5. c 13. b
6. g 14. c
7. a 15. e
8. d
2. more, more 10. c
3. h 11. a
4. b 12. True
5. c 13. b
6. g 14. c
7. a 15. e
8. d
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