UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
BIOMEDICAL IMPORTANCE
• glycoproteins = proteins that contain oligosaccharide chains
(glycans) covalently bound to AA
• glycosylation = the enzymic attachment of sugars; is the most
frequent posttranslational modification of proteins (at least half of all
eukaryotic proteins have sugars attached)
• proteins can undergo reversible glycosylation with a single sugar (N-
acetylglucosamine) bound to a serine or threonine residue (also a
site for reversible phosphorylation) — important mechanism of
metabolic regulation
• glycation = nonenzymic attachment of sugars to proteins; can have
serious pathological consequences (eg, in poorly controlled DM)
• glycoconjugate or complex carbohydrate = molecules containing
one or more CHO chains covalently linked to protein (glycoproteins
or proteoglycans) or lipid (glycolipids)
• almost all the human plasma proteins (exception of albumin) are
glycoproteins
- many proteins of cellular membranes contain substantial
amounts of CHO
- many membrane proteins are anchored to the lipid bilayer by a
glycan chain
- a number of blood group substances (others are
glycosphingolipids)
- peptide hormones
• metastasis = major problem in cancer; accumulating evidence that
alterations in the structures of glycoproteins and other
glycoconjugates on the surface of cancer cells are important in
metastasis
GLYCOPROTEINS OCCUR WIDELY & PERFORM
NUMEROUS FUNCTIONS
• glycoproteins occur in most organisms (from bacteria to human
beings, viruses)
• glycoproteins in viruses = some play key roles in viral attachment to
host cells (eg, HIV-1 and influenza A virus)
• a wide range of functions (Table 46–1) — carbohydrate content
ranges from 1% to over 85% by weight
• the glycan structures of glycoproteins change in response to signals
involved in cell differentiation, normal physiology, and neoplastic
transformation = result of different expression patterns of
glycosyltransferases under different conditions
• Table 46–2 lists some of the major functions of the glycan chains of
glycoproteins
OLIGOSACCHARIDE CHAINS ENCODE BIOLOGICAL
INFORMATION
• secondary information (rather than primary) in the sequence and
linkages of sugars in glycans — differs from DNA, RNA, and
proteins
• pattern of glycosylation depends less on its AA sequence than on:
- pattern of expression of glycosyltransferases in the cell
that are involved in glycoprotein synthesis
- affinity of the different glycosyltransferases for their CHO
substrates
- relative availability of the different CHO substrates
✴ because of this there is microheterogeneity of glycoproteins;
not all glycan chains of a given glycoprotein are complete; some
are truncated
• information from sugars = expressed via interactions between
glycans and proteins such as lectins or other molecules
- interactions lead to changes of the cellular activity —
deciphering the sugar code of life (one of the principal aims of
glycomics) involves elucidating all interactions that sugars and
sugar-containing molecules participate in, and the results of
these interactions on cellular behavior
VARIOUS TECHNIQUES ARE AVAILABLE FOR DETECTION, PURIFICATION,
STRUCTURAL ANALYSIS & SYNTHESIS OF GLYCOPROTEINS
EIGHT SUGARS PREDOMINATE IN HUMAN
GLYCOPROTEINS
• about 200 monosaccharides are found in nature
• only eight are commonly found in the oligosaccharide chains of
glycoproteins (Table 46–4, ch 15)
• N- acetylneuraminic acid (NeuAc) = usually found at the termini of
oligosaccharide chains, attached to subterminal galactose (Gal) or
N -acetylgalactosamine (GalNAc) residues
• other sugars listed are generally found in more internal positions
• Sulfate is often found in glycoproteins, usually attached to Gal,
GalNAc, or GlcNAc
✴ the sialic acids are N - or O -acyl derivatives of neuraminic acid
✴ neuraminic acid is a nine carbon sugar derived from
mannosamine (an epimer of glucosamine) and pyruvate; sialic
acids are constituents of both glycoproteins and gangliosides
SUGAR NUCLEOTIDES ACT AS SUGAR DONORS IN
MANY BIOSYNTHETIC REACTIONS
• most biosynthetic reactions = not the free or phosphorylated sugar
is involved but the corresponding sugar nucleotide
• sugar nucleotides involved in the biosynthesis: listed in Table 46–4;
some contain UDP, others guanosine (GDP) or cytidine (CMP)
• most nucleotide sugars are formed in the cytosol — generally from
reactions involving the corresponding nucleoside triphosphate
• CMP-sialic acids are formed in the nucleus
• Uridine diphosphate galactose (UDP-Gal) formation = requires 2
reactions in mammalian tissues: catalyzed by UDP-glucose
pyrophosphorylase and UDP-glucose epimerase:
• carrier systems (permeases and transporters) = required to
transport nucleotide sugars across the Golgi membrane because
many glycosylation reactions occur within the lumen of the Golgi
• antiporter systems = transports UDP-Gal, GDP-Man, and CMP-
NeuAc
- influx of one molecule of sugar nucleotide is balanced by the
efflux of one molecule of the corresponding nucleotide (UMP,
GMP, or CMP) formed from the sugar nucleotide sugars
- this mechanism ensures an adequate concentration of each
nucleotide sugar inside the Golgi apparatus
• UMP is formed from UDP-Gal in reactions catalyzed by galactosyl
transferase and nucleoside diphosphate phosphatase:
THE MAMMALIAN ASIALOGLYCOPROTEIN RECEPTOR IS
INVOLVED IN CLEARANCE OF GLYCOPROTEINS FROM
PLASMA BY HEPATOCYTES
• treatment of the protein with neuraminidase removes the terminal N-
acetylneuraminic acid moiety, exposing the subterminal galactose
residue (if terminal sialic acid residues are removed from
glycoproteins, the resulting proteins is an asialoglycoprotein)
• this asialoglycoprotein is cleared from the circulation very much
faster than the intact glycoprotein
• liver cells contain an asialoglycoprotein receptor that recognizes the
galactose moiety of many desialylated plasma proteins and leading
to their endocytosis and catabolism
LECTINS CAN BE USED TO PURIFY GLYCOPROTEINS & TO INVESTIGATE THEIR
FUNCTIONS
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UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
THREE MAJOR CLASSES OF GLYCOPROTEINS • important properties of mucins =

• divided based on the nature of the linkage between the polypeptide

and oligosaccharide chains:
1. O-glycosidic linkage (O-linked) — hydroxyl side chain of Ser or
Thr (sometimes Tyr) and a sugar like N-acetylgalactosamine
(GalNAc-Ser[Thr])
2. N-glycosidic linkage (N-linked) — amide nitrogen of Asn and N-
acetylglucosamine (GlcNAc-Asn)
3. glycosylphosphatidylinositol-anchored (GPI-anch.) glycoproteins
— linked to the carboxyl terminal AA of a protein via a phosphoryl-
ethanolamine moiety joined to an oligosaccharide (glycan), which
in turn is linked via glucosamine to phosphatidylinositol (PI)
✴involved in directing glycoproteins to the apical or basolateral
areas of the plasma memb. (PM) of polarized epithelial cells
• number of oligosaccharide chains attached to one protein can vary
from 1 to >30, with sugar chains ranging from one or two residues in
length to much larger structures
• glycan chain may be linear or branched
• many proteins contain >1 type of sugar chain (ex: glycophorin, an
important RBC membrane glycoprotein, contains both O - and N -
linked oligosaccharides)
Secretory mucins
• oligomeric structure, with monomers linked by disulfide bonds =
hence very high molecular mass
• mucus has a high viscosity; often forms a gel because of its mucin
content = intermolecular noncovalent interactions between sugars
on neighboring glycan chains contribute to gel formation
• high content of O-glycans confers an extended structure = partly
explained by steric interactions between the GalNAc moieties and
adjacent AA, resulting in a chain-stiffening effect, so that the
conformation of mucins often become rigid rods
• high content of NeuAc and sulfate residues = gives a (-) charge
Membrane-bound mucins
• participate in cell-cell interactions
• may also mask cell surface Ag = many cancer cells form large
amounts of mucins that mask surface Ag and protect the cancer
cells from immune surveillance
• carry cancer-specific peptide and carbohydrate epitopes
• some of these have been used to stimulate an immune response
against cancer cells

GLYCOPROTEINS CONTAIN SEVERAL TYPES OF O-Linked Glycoproteins Synthesis

O-GLYCOSIDIC LINKAGES
4 subclasses are found:
1. GalNAc-Ser(Thr) link = predominant link; can be found in mucins;
usually a Gal or an NeuAc residue is attached to the N -acetylgal;
many variations in the sugar compositions and lengths of such
oligosaccharide chains are found
2. Gal-Gal-Xyl-Ser trisaccharide (link trisaccharide) = proteoglycans
3. Gal-Hydroxylysine (Hyl) linkage = collagens
4. GlcNAc-Ser[Thr] = many nuclear and cytosolic proteins
contain side chains consisting of a single N -acetylglucosamine
attached to a serine or threonine residue

Mucins
• glycoproteins with two distinctive characteristics:
• most glycoproteins are membrane-bound or secreted = their mRNA
1. a high content of O-linked oligosaccharides (CHO >50%)
is usually translated on membrane-bound polyribosomes
2. presence of repeating AA sequences or variable numbers of
• glycan chains are built up by the sequential donation of sugars
tandem repeats (VNTRs) of peptide sequence in the centre
from sugar nucleotides, catalyzed by glycoprotein
of their polypeptide backbones, to which O-glycan chains are
glycosyltransferases (41 different types)
attached in clusters - Families of glycosyltrans. = named for sugar nucleotide donor
✴tandem repeat sequences = rich in Ser, Thr, and Pro - subfamilies = basis of the linkage formed between the sugar
✴up to 60% of dietary requirement for Thr = for synthesis of mucins and the acceptor substrate
• mucins contain O-glycans (predominate) and often N-glycan chains - transfer may occur with retention or inversion of the
• mucus (about 5% mucin solution) secreted by the GI, respiratory, conformation at C-1 of the sugar
and reproductive tracts - show a high degree of specificity for the acceptor substrate,
• functions: typically acting only on the product of the preceding reaction
- help to lubricate and form a protective physical barrier on
• Binding of the sugar nucleotide to the enzyme = conformational
epithelial surfaces
- highly resistant to proteolysis = density of oligosaccharide change in the enzyme = permits binding of the acceptor substrate
• Different stages in glycan formation and glycosyltransferases are
chains makes it difficult for proteases to access their
located in different regions of the Golgi = there is spatial separation
polypeptide backbones
of the different steps in the process
• secretory and membrane-bound mucins occur
• Not all of the glycan chains of a given glycoprotein are complete —
some truncated = leading to microheterogeneity
• No consensus sequence is known to determine which Ser and Thr
residues are glycosylated, but the first sugar moiety incorporated is
usually GalNAc

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UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
N-LINKED GLYCOPROTEINS
• major class of glycoproteins, including both membrane-bound and
circulating glycoproteins
• distinguished by the presence of the Asn—GlcNAc linkage
• three major classes — have the same branched pentasaccharide,
Man3GlcNAc2, bound to Asn, but differ in their outer branches
‣ complex
- contain 2, 3, 4, or 5 outer branches (oligosac branches —
often referred to as antennae = so that bi-, tri-, tetra-, and
pentaantennary structures may all be found)
- generally contain terminal NeuAc acid residues and
underlying galactose and GlcNAc residues, the latter often
constituting the disaccharide N-acetyllactosamine
- Repeating N-acetyllactosamine units —[Galβ 1–
3/4GlcNAcβ 1–3]n (poly- N -acetyllactosaminoglycans)— =
often found on N -linked glycan chains
- I/i blood group substances belong to this class
- a bewildering number of chains of the complex type exist
- other complex chains may terminate in galactose or fucose
‣ hybrid = contain features of both of the other classes
‣ high-mannose = typically have 2-6 additional mannose residues
linked to the pentasaccharide core
Biosynthesis of N-Linked Glycoproteins
• common pentasaccharide in N -linked share an initial common
mechanism of biosynthesis = thus a cotranslational modification
• In many of the N -linked glycoproteins there is a consensus
sequence of Asn-X-Ser/Thr (where X = any AA other than Pro) to
determine the site of glycosylation; in others = no clear consensus
Steps:
1. reaction between UDP-GlcNAc and dolichol phosphate = form
GlcNAc-dolichol pyrophosphate on the cytosolic side of the ER
membrane
2. second GlcNAc is added from UDP-GlcNAc
3. addition of 5 molecules of mannose from GDP-mannose
4. translocation of dolichol PP oligosaccharide into the ER lumen
5. further glycosylation = formation of the final dolichol
pyrophosphate oligosaccharide = further addition of mannose and
glucose molecules using dolichol-phosphate mannose and
dolichol phosphate-glucose as donors
6. dolichol pyrophosphate oligosaccharide is then transferred by an
oligosaccharyltransferase onto the acceptor asparagine residue
of the nascent protein chain (acceptor apoglycoprotein) as it
enters the ER during synthesis on membrane-bound
polyribosomes
• form high-mannose chains = glucose and some peripheral
mannose residues are removed by glycosidases
• form an oligosaccharide chain of the complex type = glucose and 4
of the mannose residues are removed by glycosidases in the ER
and Golgi, then GlcNAc, Gal, and NeuAc are added in reactions
catalyzed by glycosyltransferases in the Golgi apparatus
• form hybrid chains = by partial processing, forming complex chains
on one arm and mannose units on the other arm
✴Dolichol phosphate has an isoprene unit (n = 17-20 iso units)
Glycoproteins & Calnexin Ensure Correct Folding of Proteins in
the Endoplasmic Reticulum
• Calnexin is a chaperone protein in the ER membrane; binding to
calnexin prevents a glycoprotein from aggregating
• Calnexin is a lectin, recognizing specific CHO sequences in the
glycan chain of the glycoprotein
• incorrectly folded glycoproteins undergo partial deglycosylation then
targeted to transport it from the ER back to cytosol for catabolism
• calnexin binds to glycoproteins that has a monoglycosylated core
structure where the terminal glucose residue has been removed,
leaving only the innermost glucose attached
- calnexin and bound glycoprotein form a complex with ERp57
✴ ERp57 = a homolog of protein disulfide isomerase; catalyzes
disulfide bond interchange, facilitating proper folding
- bound glycoprotein is released from its complex with calnexin-
ERp57 when the sole remaining glucose is hydrolyzed by a
glucosidase and is then available for secretion if properly folded
✴ not properly folded = a glucosyltransferase recognizes this
and reglucosylates the glycoprotein, which rebinds to the
calnexin-Erp57 complex
✴ if now properly folded = the glycoprotein is again
deglucosylated and secreted
✴ if not capable of proper folding = translocated out of the ER
into the cytosol for catabolism
• glucosyltransferase senses the folding of the glycoprotein and only
reglucosylates misfolded proteins
• calreticulin = soluble ER protein; similar function to calnexin
Several Factors Regulate the Glycosylation of Glycoproteins
• glycosylation = complex process involving a large no. of enzymes
• about 1% of the human genome codes for genes involved
• at least ten distinct GlcNAc transferases
• multiple species of the other glycosyltrans (eg, sialyltrans) also exist
• Controlling factors in the first stage of N -linked glycoprotein
biosynthesis (assembly and transfer of the dolichol PP oligosac)
- availability of the sugar nucleotides
- presence of suitable acceptor sites in proteins
- the tissue concentration of dolichol phosphate
- activity of the oligosaccharide: protein transferase
• Species variations among processing enzymes = important in
production of glycoproteins of therapeutic use by means of
recombinant DNA technology
• recombinant erythropoietin (EPO) = patients with some types
of chronic anemia = to stimulate erythropoiesis
• half-life of EPO in plasma = influenced by glycosylation pattern
• some patterns = short half-life, limiting therapeutic effectiveness
(important to harvest EPO from host cells that confer a pattern of
glycosylation consistent with a normal half-life in plasma)
• activities of glycoprotein-processing enzymes in cancer cells =
synthesize different oligosac chains from those made in normal cells
(exhibit greater branching) = differences affect adhesive interactions
between cancer cells and normal parent tissue cells = metastasis
• could be due different patterns of glycosyltrans as a result of
specific gene activation or repression
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UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
• factors involved in the regulation of oligosaccharide processing:
SOME PROTEINS ARE ANCHORED TO THE PM BY
GLYCOPHOSPHATIDYL-INOSITOL STRUCTURES
• third major class of glycoproteins is the membrane-bound proteins
anchored to the lipid bi by a glycophosphatidylinositol (GPI) tail
• GPI linkage = commonest way proteins are anchored to cell memb.
• proteins are anchored to the outer leaflet of the PM or the inner
(luminal) leaflet in secretory vesicles by the fatty acids of
phosphatidylinositol
- phosphatidylinositol is linked via GlcNA to a glycan chain
containing a variety of sugars (includes mannose, glucosamine)
- oligosac chain is linked via phosphorylethanolamine in an
amide link to the carboxyl terminal AA of the attached protein
• additional constituents are found in many GPI structures
• Examples of some proteins anchored by GPI-linkage:
• There are three possible functions of this GPI-linkage:
1. GPI anchor allows greatly enhanced mobility of a protein in the
PM (compared with a protein containing transmembrane seq.)
- GPI anchor is attached only to the outer leaflet = freer to diffuse
(than protein anchored through both layers of the membrane)
- increased mobility = impt in facilitating rapid responses to stimuli
2. Some GPI anchors connect with signal transduction pathways =
proteins that don’t have a transmembrane domain may be
receptors for hormones and other cell-surface signals
3. GPI structures can target proteins to apical or basolateral domains
of the PM of polarized epithelial cells
• GPI anchor = preformed in the ER and then attached to the protein
after ribosomal synthesis is complete
• primary translation products of GPI-anchored proteins have
- an amino terminal signal sequence that directs them into the ER
during synthesis
- a carboxy terminal hydrophobic domain = acts as the signal for
attachment of the GPI anchor
• synthesis of the GPI anchor
1. insertion of the FA of phosphatidylinositol into the luminal
face of the ER membrane
2. glycosylation, starting with esterification of GlcNA to the
phosphate group of phosphatidylinositol
3. terminal phosphoethanolamine moiety is added to the
completed glycan chain
4. hydrophobic carboxy terminal domain of the protein is
displaced by the amino group of ethanolamine in the
transamidation reaction that forms the amide link between
the GPI anchor and an aspartate residue in the protein
SOME PROTEINS UNDERGO RAPIDLY REVERSIBLE
GLYCOSYLATION
• Many proteins undergo O-glycosylation with a single sugar moiety,
GlcNAc — rapidly reversible glycosylation
- (including nuclear pore proteins, proteins of the cytoskeleton,
transcription factors, proteins associated with chromatin, nuclear
oncogene proteins, tumor suppressor proteins)
• Ser and threonine sites of glycosylation = same as phosphorylation
• glycosylation and phosphorylation occur reciprocally in response to
cellular signaling
• O -linked GlcNAc transferase
- catalyzes this — uses UDP-GlcNAc as the sugar donor
- has phosphatase activity = can directly replace a serine or
threonine phosphate with GlcNAc
✴no absolute consensus sequence for the reaction but about
half the sites subject to reciprocal glycosylation and
phosphorylation are Pro-Val-Ser
- activated by phosphorylation in response to insulin action =
GlcNAc is removed (leaving the site available for
phosphorylation) by N -acetylglucosaminidase
- activity and peptide specificity of O -linked GlcNAc
transferase depend on the concentration of UDP-GlcNAc
• Depending on cell type, 2% to 5% of glucose metabolism is by way
of hexosamine pathway leading to GlcNAc formation, giving the
O-linked GLcNAc transferase a role in nutrient sensing in the cell
• Excessive O -glycosylation with GlcNAc (reduced phosphorylation)
of target proteins = insulin resistance and glucose toxicity in
diabetes mellitus , as well as neurodegenerative diseases
ADVANCED GLYCATION END-PRODUCTS (AGEs) ARE
IMPORTANT IN CAUSING TISSUE DAMAGE IN DM
• Glycation = nonenzymic attachment of sugars (mainly glucose) to
amino groups of proteins (also other mol. including DNA, lipids)
1. glucose forms a Schiff base to the amino group protein
2. undergoes Amadori rearrangement to yield ketoamines ;
undergo further reactions to yield advanced glycation end-
products (AGEs)
• Maillard reaction = overall series of reactions; involved in the
browning of certain food during storage or heating, provides much
of the flavor of some foods
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UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
• AGEs underlie tissue damage in poorly controlled DM
- when blood glucose conc is consistently elevated = increased
glycation of proteins
- glycation of collagen and other proteins in the ECM alters their
properties (eg, increasing the cross-linking of collagen)
✴ Cross-linking can lead to accumulation of various plasma
proteins in the walls of BV; in particular, accumulation of LDL
= contribute to atherogenesis.
• AGEs =involved in microvascular and macrovascular damage in DM
• Endothelial cells and macrophage surfaces have AGE receptors
- uptake of glycated proteins by these receptors can activate the
transcription factor NF-kB, generating a variety of cytokines
and proinflammatory molecules
- AGEs = significant contributor to some pathology of diabetes
• Glycation of hemoglobin A leads to the formation of HbA1c
- occurs normally to a modest extent; increased in patients with
DM with poor glycemic control, whose blood glucose conc is
consistently elevated
- measurement of HbA1c = very important part of the
management of patients with DM
GLYCOPROTEINS ARE INVOLVED IN MANY BIOLOGIC
PROCESSES & IN MANY DISEASES
• Table 46–1 = glycoproteins have many different functions
• they are also important in fertilization and inflammation
• a number of diseases are due to defects in the synthesis and
catabolism of glycoproteins
Glycoproteins Are Important in Fertilization
Selectins Play Key Roles in Inflammation & in Lymphocyte Homing
Abnormalities in the Synthesis of Glycoproteins
• many cancer cells exhibit different profiles of oligosaccharide
chains on their surfaces = some may contribute to metastasis
• Leukocyte adhesion deficiency II
- rare condition
- mutations affecting activity of a Golgi located GDP-fucose
transporter; absence of fucosylated ligands for selectins =
marked decrease in neutrophil rolling
- suffer life-threatening, recurrent bacterial infections,
psychomotor and mental retardation
- appears to respond to oral fucose
• Paroxysmal nocturnal hemoglobinuria
- acquired mild anemia
- characterized by the presence of Hgb in urine due to hemolysis
of red cells, particularly during sleep (slight drop in plasma pH =
increases susceptibility to lysis by the complement system)
- due to the acquisition in hematopoietic cells of somatic
mutations in the gene coding for the enzyme that links
glucosamine to phosphatidylinositol in the GPI structure
✴leads to a deficiency of proteins that are anchored to the red
cell membrane by GPI-linkage
- decay accelerating factor and CD59 normally interact with
components of the complement system to prevent hemolysis
✴When deficient, the complement system acts on the red cell
membrane to cause hemolysis
• Some of the congenital muscular dystrophies (CMDs)
- defects in the synthesis of glycans in the protein α -dystroglycan
✴ protein protrudes from the surface membrane of muscle cells
and interacts with laminin-2 (merosin) in the basal lamina
- If glycans of α -dystroglycan are not correctly formed (result of
mutations in genes encoding some glycosyltransferases) =
results in defective interaction of α -DG with laminin
• Rheumatoid arthritis
- associated with an alteration in the glycosylation of circulating
IgG molecules, such that they lack galactose in their Fc regions
and terminate in GlcNAc
• Mannose-binding protein
- a lectin synthesized by liver cells and secreted into the
circulation
- binds mannose, GlcNAc, and some other sugars = can thus
bind agalactosyl IgG molecules, which subsequently activate
the complement system, contributing to chronic inflammation in
the synovial membranes of joints
- innate immunity (not involving Ig or T lymphocytes) = MBP
can also bind sugars when they are present on the surfaces of
bacteria, fungi, and viruses = preparing these pathogens for
opsonization or for destruction by the complement system
- Deficiency in young infants as a result of mutation = susceptible
to recurrent infections
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UNIT II ⫸ Glycoproteins (Chapter 46 — Harper’s)
Inclusion Cell (I-Cell) Disease Results from Faulty Targeting of
Lysosomal Enzymes
• Mannose 6-phosphate = target enzymes into the lysosome
• uncommon condition characterized by severe progressive
psychomotor retardation and a variety of physical signs, with death
often occurring in the first decade of life
• cells lack almost all of the normal lysosomal enzymes = lysosomes
accumulate many undegraded molecules, forming inclusion bodies
• patients’ plasma = very high activities of lysosomal enzymes —
enzymes are synthesized but fail to reach their proper intracellular
destination and are instead secreted
• Cultured cells from patients take up exogenously added lysosomal
enzymes obtained from normal subjects = cells have a normal
receptor on their surfaces for endocytic uptake of lysosomal
enzymes
• Lysosomal enzymes from normal individuals carry the M6P
recognition marker
• cells from patients with I-cell disease lack the Golgi-located GluNAc
phosphotransferase
• Two lectins act as M6P receptor proteins — both function in the
intracellular sorting of lysosomal enzymes into clathrin-coated
vesicles in the Golgi = these vesicles then leave the Golgi and fuse
with a prelysosomal compartment

Genetic Deficiencies of Glycoprotein Lysosomal Hydrolases Cause Diseases Such as

α-Mannosidosis

GLYCANS ARE INVOLVED IN THE BINDING OF VIRUSES, BACTERIA, & SOME

PARASITES TO HUMAN CELLS
• Glycoproteins are also involved in many other diseases, including
influenza, AIDS, rheumatoid arthritis, cystic fibrosis and peptic ulcer