Chapter 11 Carbs and glycoproteins BIOCHEM

exam 3

Carbohydrates

carbon-based molecules high in
hydroxyl groups,

formula (CH2O)n

Monosaccharides

aldehydes or ketones that contain
two or more hydroxyl groups.
• They are three to seven carbons in length
• Monosaccharides exist in many isomeric forms and are
also called simple sugars.

constitutional isomers

molecules with identical
molecular formulas that differ in how the atoms are
ordered

sterioisomers

molecules that differ in spatial arrangement but not bonding order

have either D or L configuration
– can be enantiomers (mirror images of each other) or
diastereoisomers (not mirror images of each other)
– number possible = 2ⁿ where n is the number of asymmetric
carbon atoms

anomer

a diastereoisomeric form of sugars that forms
when a cyclic hemiacetal is formed and an additional
asymmetric center is created

epimers

sugars that are diastereomers differing in configuration only at a single asymmetric center (think of all the sugars, sometimes only one H and OH switched)

blood sugar

D-glucose circulating in the blood

only fuel by the brain in non starvation conditions

only fuel used by RBCs

reasons why D-glucose is an important fuel

1. formed from formaldehyde under prebiotic conditions (primitive biochemical systems)

2. relatively inert

3. most stable ring structure is β-D-glucopyranose

glycation

nonenzymatic addition of a carbohydrate to another molecule

example: Reducing sugars nonspecifically react with free amino
groups on proteins (often Lys or Arg) to form a stable covalent bond.

advanced glycation end products (AGEs)

products resulting from
cross-linking following the primary modification
– implicated in aging, arteriosclerosis, diabetes, and other
pathological conditions

A1c

D-glucose reacts with hemoglobin to form glycated hemoglobin

Diabetes and glycation

patients with uncontrolled diabetes almost 10% of hemoglobin is glycated (lots of glucose on RBCs), Only eliminated when RBC’s die
(lifespan is about 120 days)

O-glycosidic linkage

covalent linkage formed between
the anomeric carbon atom of a carbohydrate and the
oxygen atom of an alcohol

N-glycosidic linkage

covalent linkage formed between
the anomeric carbon atom of a carbohydrate and the
nitrogen atom of an amine

oligosaccharides

sugars that contain two or more
monosaccharides linked by O-glycosidic bonds
– have directionality defined by their reducing and
nonreducing ends

reducing end of oligosaccharide

has a free anomeric carbon atom that
can form the open-chain form

nonreducing end

has an anomeric carbon in a
glycosidic linkage that cannot covert to the open-chain
form

α-1,4-glycosidic linkage

glycosidic linkage between the
α-anomeric form of C-1 on one sugar and the hydroxyl
oxygen atom on C-4 of the adjacent sugar

disaccharide

two sugars
joined by an O-glycosidic
linkage
• Cleavage products of
disaccharides can be
processed to provide
energy in the form of ATP.

sucrose

disaccharide of sugar cane or sugar beets that consists
of glucose linked to fructose
– the anomeric carbon of glucose is linked to the anomeric carbon
of fructose
– the configuration is α for glucose and β for fructose
– not a reducing sugar
– can be cleaved by sucrase (invertase)

Lactose

disaccharide of
milk that consists of a
galactose linked to a
glucose
– linked by a β-1,4-
glycosidic linkage.
– can be hydrolyzed by
lactase in human
beings and by β-
galactosidase in
bacteria
– Lack of lactase leads
to lactose intolerance

maltose

disaccharide resulting from the hydrolysis of
large oligosaccharides that consists of two linked
glucose molecules
– joined by an α-1,4-glycosidic linkage
– can be hydrolyzed to glucose by maltase (α-glucosidase )

polysaccharides (glycans)

large polymeric
oligosaccharides formed by the linkage of multiple
monosaccharides
– plays roles in energy storage and structural integrity

homopolymer

polymer in which all the monosaccharide units are the same

glycogen

large, branched polymer of glucose residues
– most common
homopolymer in animal
cells
– storage form of glucose
– most glucose units are
linked by α-1,4-glycosidic
linkages
– branches are formed by
α-1,6-glycosidic linkages —> larger surface area better access for enzymes
– hydrolyzed by α-amylase

starch

homopolymer that serves as the nutritional
reservoir in plants
– two forms: amylose and amylopectin• Amylose and amylopectin are hydrolyzed by α-amylase.

amylose

unbranched type of starch composed of
glucose residues in α-1,4 linkage

amylopectin

branched type of starch with ~1 α-1,6
linkage per 30 α-1,4 linkages
– identical structure to glycogen but with a lower degree of
branching

Insoluble fibers

increase the rate at which digestion
products pass through the large intestine.
– softens stools and makes them easier to pass

Soluble fibers

slow the
movement of food through the
gastrointestinal tract.
– facilitates absorption of
nutrients from the diet

chitin

chitin = homopolymer of β-1,4
linked N-acetylglucosamine
– found in fungal cell walls and
exoskeletons and shells of
arthropods
– Fibers are often crosslinked
and composited with minerals
and proteins to increase rigidity
and strength.

glycoprotein

a carbohydrate group covalently attached
to a protein
– makes up 50% of the human proteome
• glycosylation increases the complexity of the proteome

ADHESION

Proteoglycans

the predominant molecule is a carbohydrate and
the protein component is conjugated to a glycosaminoglycan
– function as structural components and lubricants

mucins (mucoproteins)

predominant molecule is a
carbohydrate and the protein components is extensively
glycosylated at Ser or Thr residues, usually by N-
acetylgalactosamine
– key component of mucus
– function as lubricants

N-linkage (glycoproteins)

links the sugars in
glycoproteins to the amide
nitrogen atom in the side chain
of Asn
– Asn must be part of an Asn-X-
Ser or Asn-X-Thr sequence,
where X is any residue except
proline

O-linkage

links the sugars in
glycoproteins to the oxygen
atom in the side chain of Ser
or Thr

erythropoietin (EPO)

a
glycoprotein secreted by the
kidneys into the blood serum
to stimulate production of
red blood cells
– cloned recombinant form
has improved treatment for
anemia, but has been
abused by some endurance
athletes
– glycosylation enhances the
stability of the protein in the
blood

GlcNAcylation

the post-
translational, covalent
attachment of a single N-
acetylglucosamine
(GlcNAc) to Ser or Thr
residues of proteins
– catalyzed by O-GlcNAc
transferase
– occurs when nutrients are
abundant
– reversible

O-GlcNAc Transferase

GlcNAcylation sites are also potential phosphorylation
sites.
- and protein kinases may be
involved in cross talk.
• Improper regulation of O-GlcNAc transferase has been
linked to:
– insulin resistance.
– diabetes.
– cancer.
– neurological pathologies.

functions of proteoglycans

are up to 95% glycosaminoglycan by
weight)
– resembles a polysaccharide more than a protein

– function as lubricants and structural components in
connective tissue.
– mediate adhesion of cells to extracellular matrix.
– bind factors that regular cell proliferation.

glycosaminoglycans

composed of repeating units of
disaccharides containing a derivative of an amino sugar
– amino sugar derivative is either glucosamine or
galactosamine
– at least one of the two sugars in the unit has a negatively
charged carboxylate or sulfate group
• The inability to degrade causes
diseases marked by skeletal deformities and reduced life
expectancies.

aggrecan

large molecule with three globular domains
– site of glycosaminoglycan (keratan sulfate and chondroitin
sulfate) attachment is in the extended region between G2
and G3
– G1 non covalently binds to a central polymer of
hyaluronate

osteoarthritis

form of arthritis that results when water is lost from
proteoglycan with aging

tandem repeats (VNTR) region

region of the protein
backbone of mucins that is rich in O-glycosylated Ser
and Thr residues
• Core carbohydrate structures are conjugated to the
protein component of mucin.

functions of mucins

adhere to epithelial cells and act as a protective barrier.
– hydrate the underlying cells.
– play roles in fertilization, the immune response, and cell
adhesion.
• Overexpression occurs in bronchitis, cystic fibrosis, and
adenocarcinomas.

Golgi complex

a stack of
flattened membranous
sacs
• proteins proceed to
lysosomes, secretory
granules, or the plasma
membrane
– based on signals
encoded within their
amino acid sequences
and three-dimensional
structures

glycosyltransferases

catalyze the formation of
glycosidic linkages
• Activated sugar nucleotides are the most common
carbohydrate donor for

type A transferase

adds N-acetylgalactosamine to galactose moiety of the o antigen

type B transferase

adds galactose to galactose moiety of the o antigen

Lysosomes

organelles that degrade and recycle
cellular components or endocytosed material

I-cell disease

a lysosomal storage disease that causes
severe psychomotor impairment and skeletal deformities
– affected lysosomes contain undigested
glycosaminoglycans and glycolipids
– active enzymes responsible for degradation are
synthesized but they lack appropriate glycosylation and are
exported instead of delivery to lysosomes

glycan-binding proteins

bind to specific carbohydrate
structures on neighboring cell surfaces

lectins

class of glycan-binding proteins
– example: the mannose 6-phosphate receptor that binds
and directs lysosomal enzymes to the lysosome

role of lectins

function to facilitate cell–cell contact.
– usually contains 2+ carbohydrate-binding sites.
– are linked to carbohydrates by a number of weak
noncovalent interactions

*C-type (calcium-requiring) lectins

found in animals
– function in receptor-mediated endocytosis and cell–cell
recognition

L-type lectins

rich in seeds of leguminous plants
– serve as potential toxins to herbivorous insects
– come act as chaperones in the eukaryotic ER

selectins

bind immune-system cells to
sites of injury in the
inflammatory response
– play a role in recruiting
leukocytes to inflammation
sites

L form

bind to carbohydrates
on lymph-node vessels

E form

bind to carbohydrates
on endothelium

P form

bind to carbohydrates
on activated blood platelets

hemagglutinin

influenza virus lectin protein that binds
to carbohydrates sialic acid residues linked to galactose
residues on cell-surface glycoproteins
– the virus is engulfed after binding
• The virus replicates inside the cell and viral particles bud
off from the cell.

neuraminidase (sialidase)

influenza virus protein that
cleaves the glycosidic linkages between sialic acid and
the rest of the glycoprotein
– frees the virus to infect new cells
– inhibitors of neuraminidase (Tamiflu and Relenza) are
important anti-influenza agents