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Glycoconjugates

Liz Jhorimar Herrera Moron Spanish

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Glycoconjugates

They are glycosides
- Linked to proteins or lipids
  - Through covalent bonds
Function
- Transport information
- They act on cell recognition and addition
- Provide structural integrity
  - To cells and tissues
- Structural Glycans
  - Passive Signaling Functions
- Influences
  - Control systems
    - Protein quality
      - Secretory pathway
- Interactions between receptor and ligand
- Regulation of endocytosis
  - And
    - Protein trafficking
- Membrane organization and signaling
- Nutrient storage
- Immune recognition and evasion
- Cell-cell interactions
  - During fertilization
- Glucans play
  - Key role in human health and disease
Where are they found?
- With proteins
  - Proteoglycans
    - They can be from
      - Hyaluronic acid
      - Chondroitin sulfate
      - Keratan sulfate
  - Glycoproteins
    - Linked by –O to
      - Serine or threonine bonds
    - Linked by –N to
      - Asparagine links
    - Immunoglobulins
    - Major histocompatibility complex
- With lipids
  - Glycolipids
    - Found in
      - Plasma membrane
  - Lipopolysaccharides
    - Found in
      - Bacterial membrane
    - Immune system
      - Reception mechanisms
        To attack bad bacteria
How do we obtain the sugars that can be incorporated?
- They are modified sugars
  - And
    - They become
      - Other types of sugars
        This is due to
        Glucose bound to any biomolecule
        Harmful
        Nucleotides are added to them
        To be recognized
        Uridine dysphosphate
        Galactose and glucose
        Guanusine diphosphate
How is the incorporation process done?
- One is made
  - Interconversion between sugars
    - Special sugars
      - what is called
        Sialic acid
        N acetyl glucosamine
Types of glycocongugates
- Glycosaminoglycans
  - There are 7
    - Ialuronate or yaluronic acid
      - Glucoronate + N acetyl glucosamine
    - Dermatan sulfate
      - Iduronate + N acetyl galactosamine sulfate
    - Chondroitin sulfate
      - Glucoronate + N acetyl galactosamine sulfate
    - Heparin and heparan sulfate
      - Iduronate + Sulfo N acetyl glucosamine phosphate
    - Keratan sulfate 1 and 2
      - D galactose + N acetyl glucosamine sulfate
    - Where are they found?
      - Ialuronic acid
        Synovial fluid
        Vitreous humor
        Extracellular matrix of connective tissue
      - Chondroitin sulfate
        Cartilage
        Bone
        Heart valves
      - Heparan sulfate
        Basement membranes
        Components of cell surfaces
      - Heparin
        Component of
        The intracellular granules
        Of the mast cells
        Which cover
        The arteries
        Lungs
        Liver
        Skin
      - Dermatan sulfate
        Blood vessels
        Skin
        Heart valves
      - Keratan sulfate
        Cornea
        Bone
        Cartilage added
  - Polysaccharide
    - Made up of
      - Repeated sequences of
        Disaccharides
        Where one of its components is
        Amino sugar
        G-glucosamine
        G-glucosamine
  - They do not have branches
    - They only form
      - Chains (linear)
  - They are the heteropolysaccharides
    - Most abundant in the body
  - Almost all
    - Possess
      - Sulfate groups
  - They are molecules
    - Negatively charged
Excess or deficit
- Excess
  - Eliminated
- Deficiency in
  - Degradation of those already synthesized
    - Old or damaged
      - Cause
        Mucopolysaccharidosis diseases
        They belong to the group of
        Orphan diseases
        They do not occur frequently
        Occurs due to
        The enzymes that degrade glycosaminoglycans
        They are not present or are deficient
        Which causes them
        They are accumulated in
        The tissues where they are
        Diseases
        Autosomal recessive disease
        Or gargolismoa
        San Philipo syndrome
        Morquio syndrome
        Hunter syndrome
        Hurler syndrome
        Sly syndrome
        Treatment
        Inject the deficient enzyme
Others
- Glycoproteins
  - Protein + oligosaccharides
    - Linked by
      - Covalent bond
  - Major component
    - Protein
  - Found in
    - Golgi Complex
    - MEC
    - Lysosomes
- Types of glycosylation
  - Enzyme-regulated sugar addition process
    - N glycosylation
    - Or glycosylation
- Proteoglycans
  - High molecular weight
    - Protein Core Block
      - Linear Sugar Chains
  - Found in
    - Extracellular Matrix
- Glycobiology
  - Study of biosynthesis
    - Structures
      - Interactions
        Functions
        Evolution of glucans
- Building Blocks of Glycans
  - Monosaccharides or individual sugars
- From protein and lipid scaffolds
  - Cells create glucans
    - Through glycosidic bonds
      - Attachment of one monosaccharide to another
        Through the hydroxyl of the anomeric carbon
- Stereochemistry is important
  - They can be almost the same
    - But have
      - Different biological properties
        Combinatorial complexity
In eukaryotic cells
- Most of
  - Glycoproteins and glycolipids
    - They biosynthesize in
      - The endoplasmic reticulum and Golgi
        Through the sequential action of
        Series of glycosyltransferases and glycosidases
        Located in specific subdomains
        Of these organelles
        Forming a
        Assembly line
        Building glycans as they
        Lipid and protein substrates
        Transit the secretory pathway
        Some
        Extracellular glucans
        Biosynthesize and extrude
        On the plasmid membrane
Glycosylation
- It is abundant within
  - Animal and plant cells
    - Thousands of soluble proteins
      - Nuclear and cytoplasmic
        They are dynamically modified in
        Serine and threonine residues
        By O-GlcNAc
        Transient modification of a single sugar
        Regulating
        Localization and protein function
Final glycoforms
- Protein and lipid
  - Depend on
    - Interaction between
      - Glycan biosynthetic machinery
        Available nucleotide sugars
        And
        Signals from
        Intracellular and extracellular environments
        Not driven by
        Pre-existing template molecule
- Due to
  - Biosynthetic complexity
    - A given protein
      - Multiple glycoforms
        Within a single cell or tissue
        Phenomenon known as
        Microheterogeneity
        Additionally
        A single protein
        May glycosylate
        Differently
        In a tissue or organ
        In front of another
        Also producing
        Macroheterogeneity
Biological imperatives
- Driving
  - Variety of glycoconjugates
    - Little known
      - But many organisms
        Use multiple glycoforms
        To generate
        Greater functional diversity
        From
        Limited set of scaffolds
        Of proteins or lipids- or
        To confuse viruses and other parasites
        Which could explode
        More easily simple and predictable
Important diseases
- Characterized by
  - Aberrant glycosylation
    - Cancer
    - Neurodegeneration
    - Diabetes
    - Congenital disorders
- Several critical treatments
  - They are themselves glycoconjugates
    - Heparin
    - Aminoglycoside antibiotics
    - Erythropoietin
    - Monoclonal antibodies
    - Many vaccines
Glycobiology
- Little studied
  - Compared to
    - Other aspects of cell biology
      - One reason for this delay is
        The chemical complexity
        And
        Analytical challenges of glucans
        They have presented formidable barriers
        To research
A large number of intracellular proteins
- They are reversibly modified by
  - O-GlcNAc in animals and plants
    - O-GlcNAc is added to substrates
      - By OGT glycosyltransferase
        Using UDP-GlcNAc
        As its nucleotide
        Sugar donor
        A predominant notion is
        O-GlcNAc often
        Serves a role de
        Nutrient detection
        Because UDP-GlcNAc itself
        It biosynthesizes from
        Various essential metabolites
        Such as
        Glucose
        Glutamine
        ATP
        Uridine
        Acetyl-coenzyme A
    - Global levels
      - Of O-GlcNAc
        Fluctuate in response
        To nutrient changes
It has been related
- With metabolically important pathways and processes
  - Such as cardiac calcium signaling
  - Circadian entrainment
  - Mitochondrial motility in neurons
  - Epigenetic transcriptional control
  - Of metabolic genes
  - The Hippo -Control pathway
    - Of the size of YAP organs

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Description: Mind Map on Glycoconjugates, created by Liz Jhorimar Herrera Moron on 15/10/2020.
Created by: Liz Jhorimar Herrera Moron
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Glycoconjugates

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