1998:%20%20%20%20%20Ph.D.%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Nagoya%20University,%20Japan

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Wei Liu (? ?) Tel[phone] E-mail
liuwei666_at_zju.edu.cn

1998 Ph.D.
Nagoya University, Japan 1999-2001
Assistant Professor Aichi Medical,
Japan 2001-2007 Research fellow,
National Institutes of Health, USA
2007-now Professor
Zhejiang University
Selective publications
Trends in Cell Biology
2006 Journal of Cell Biology
2005 Nature Structural Molecular
Biology 2005 Nature
2003 Cell Death
Differentiation 2003
Autophagy 2013 Journal of
Cell Science 2013 Hepatology
2012 Journal of Cell Science 2012 Journal of
Hepatology 2011
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????????? Laboratory of Organelle Biology
Research Interests Our laboratory is centered on
the elucidation of molecular mechanisms
underlying the endomembrane structures and
functions by use of con-focal microscopy and
analyzing protein dynamics in living cells. We
are also interested in the roles of intracellular
organelles involved in physiological and
pathological processes such as mitosis,
autophagy, aging and liver cancer development.
Endoplasmic Reticulum
Golgi apparatus(red)
Mitochondria
Peroxosome(green)
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Biochemistry
Teaching staff
Wei Liu
Jin-Biao Zhan
Li-Hong Xu
Yong-Gang Chen
Introduction Bio-molecules
Enzymes
Metabolism
Hormones DNA replication Gene expression
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What Is Biochemistry?
Overview of Biochemistry

• Biochemistry studies living systems to discover
  and understand their chemical composition and how
  organisms carry out life processes.
• Combines biology and organic, inorganic or
  physical chemistry to study life processes.

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Brief history of Biochemistry

• Originated at the end of 18th Century.
• Developed in 19th Century.
• At the beginning of 20th century, biochemistry
• became an independent science.
• It was called physiological chemistry.
• From 1903, it became Biochemistry.

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What is Life Made of?

• Physical and Chemical sciences alone may not
  completely explain the nature of life, but they
  at least provide the essential framework for such
  an explanation.
• All students of life must have a fundamental
  understanding of organic chemistry and
  biochemistry.

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Organic Chemistry

• Organic chemistry is the study of Carbon
  compounds.
• Organic compounds are compounds composed
  primarily of a Carbon skeleton.
• All living things are composed of organic
  compounds.

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Organic Chemistry
9
Organic Chemistry
Carbon can covalently bond with up to four other
atoms.
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Carbon can form immensely diverse compounds, from
simple to complex.
Methane with 1 Carbon atom
DNA with tens of billions of Carbon atoms
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Biochemistry

• Biochemistry is a special branch of organic
  chemistry that deals with matter inside the
  living cell called Protoplasm.
• Protoplasm is an enormously complex mixture of
  organic compounds where high levels of chemical
  activity occur.

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Biochemistry

• How much biochemistry do you need to know for
  this course?
• 1. You need to know the structure of organic
  molecules important to major biological
  processes.

2. You will be expected to learn the basic
biochemical processes of major cell functions,
such as protein synthesis.
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Primary Organic Compounds

• Carbohydrates
• Lipids
• Proteins
• Nucleic Acids

You are expected to learn the structure and
functions of these organic compounds
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Polymers ands Monomers

• Each of these types of molecules are polymers
  that are assembled from single units called
  monomers.
• Each type of macromolecule is an assemblage of a
  different type of monomer.

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Monomers

• Macromolecule
• Carbohydrates
• Lipids
• Proteins
• Nucleic acids

• Monomer
• Monosaccharide
• Not always polymers
• Amino acids
• Nucleotides

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How do monomers form polymers?

• In condensation reactions (also called
  dehydration synthesis), a molecule of water is
  removed from two monomers as they are connected
  together.

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Hydrolysis

• In a reaction opposite to condensation, a water
  molecule can be added (along with the use of an
  enzyme) to split a polymer in two.

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Four major classes of biomolecules
Carbohydrate Proteins
Nucleic acid
Lipids
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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds
with multiple hydroxyl
groups. Sugar
(C-H2O)n
Aldehyde -CHO
Ketone CO
Hydroxyl -OH
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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl groups. Function
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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl
groups. Function (1) serves as energy stores,
fuel, and metabolic intermediates.

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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl
groups. Function (1) serves as energy stores,
fuel, and metabolic intermediates.
(2) ribose and deoxyribose
sugars form part of the structure framework of
RNA and DNA.
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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl
groups. Function (1) serves as energy stores,
fuel, and metabolic intermediates.
(2) ribose and deoxyribose
sugars form part of the structure framework of
RNA and DNA. (3)
polysaccharides are structural elements in the
cell walls of bacteria and plants. Cellulose, the
main constituent of plant cell walls, is one of
the most abundant organic compounds in the
biosphere.
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Carbohydrates
Definition carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl
groups. Function (1) serves as energy stores,
fuels,and metabolic intermediates.
(2) ribose and deoxyribose
sugars form part of the structure framework of
RNA and DNA. (3)
polysaccharides are structural elements in the
cell walls of bacteria and plants. Cellulose, the
main constituent of plant cell walls, is one of
the most abundant organic compounds in the
biosphere. (4)
carbohydrates are linked to many proteins and
lipids, where they play key roles in mediating
interactions among cells and interactions between
cells and other elements in the cellular
environment.


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Monosaccharides are aldehydes or ketones with
multiple hydroxyl groups
The simplest carbohydrates
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D-Ketoses containing three, four, five, and six
carbon atoms
Asymmetric center
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D-Aldoses containing three, four, five, and six
carbon atoms
Asymmetric center
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The predominant forms of ribose, glucose,
fructose, and many other sugars in solution are
not open chains. Rather, the open-chain forms of
these sugars cyclize into rings.
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The predominant forms of ribose, glucose,
fructose, and many other sugars in solution are
not open chains. Rather, the open-chain forms of
these sugars cyclize into rings.
Where does the ring come from?
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An aldehyde can interact with alcohol to form
hemiacetal
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A ketone can interact with alcohol to form
hemiketal
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Pentose and hexoses cyclize to form furanose and
pyranose ring
The C-5 hydroxyl group attacks the oxygen atom of
the C-1 aldehyde group to form an intromolecular
hemiacetal.
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Pentose and hexoses cyclize to form furanose and
pyranose ring
The C-5 hydroxyl group attacks the oxygen atom of
the C-2 ketone to form an intromolecular
hemiketal.
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Fructose can form both five-membered frunose and
six-membered pyranose rings
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RNA
DNA
deoxyribonucleic acid
ribonucleic acid
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Conformation of pyranose ring
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The boat form of glucose is disfavored because of
the steric hindrance
The chair form of b-D-glucopyranose predominates
because all the axial positions are occupied by
hydrogen atoms. The bulkier OH and -CH2OH
groups emerge at the less-hindered periphery.
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Monosaccharides can be modified by reaction
with alcohols and amines to form adducts
O-Glycosidic bond between the anomeric carbon
atom of glucose and the hydroxyl oxygen atom of
methonol. N-Glycosidic bond anomeric carbon atom
nitrogen atom of an amine
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Carbonhydrates can be modified by the addition of
substituents. Such modified carbohydrates are
often expressed on cell surface
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Complex carbonhydrate are formed by linkage of
monosacchrides
Monosaccharides
O-glycosidic bonds
Oligosaccharides
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Sucrose, lactose, and maltose are the common
disaccharides from dietary components
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Sucrose, lactose, and maltose are the common
disaccharides from dietary components
sucrase
2 monosaccharides
Glycosidic bond
lactase
enzyme
Disaccharides
maltase
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Electron micrograph of a microvillus
lactose
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Glycosyltransferase
Monosaccharides
Glycosidic bond
Glycosyltransferase
Oligosaccharides
Glycosyltransferase specifically catalyze the
formation of glycosidic bonds, that means each
enzyme must be specific to the sugars being
linked.
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Carbonhydrates can be attached to ptroteins to
form glycoproteins
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Carbonhydrates can attach to ptroteins forming
glycoproteins
Glycosidic bonds between proteins and
carbohydrates
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Note 1. Carbohydrates may be linked to proteins
through asparagine (N-linked) or through serine
or threonine (O-linked) residues. 2. An
asparagine residue can accept an oligosacchride
only if the residue is part of an Asn-X-Ser or
Asn-X-Thr sequence. 3. Potential glycosylation
sites can be detected within amino acid sequences.
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Elastase, showing linked carbohydrates on its
surface
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Protein Glycosylation takes place in the lumen of
the ER and the Golgi complex
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Transport into the endoplasmic reticulum
1. A signal sequence directs the nascent
protein through channels in the ER membrane and
into the lumen. 2. The N-linked glycosylation
begins in the ER and continues in the Golgi
complex, whereas the O-linked glycosylation takes
place exclusively in the Golgi.
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Bonifacino JS and Glick BS, 2004
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• 1. Terminal glycosylation carbohydrate
  processing in the
• Golgi apparatus.
• 2. Core glycosylation takes place in the ER.
• Tremendous structural diversification can occur
  as a
• result of the terminal glycosylation
  process.

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Formation of a mannose 6-phosphate
1. Mannose 6-phosphate is a marker directing
certain proteins from the Golgi to lysosomes. 2.
Deficient in the phosphotransferase
Cant form mannose 6-phosphate
Mistargeting of essential enzymes (lysosome
blood and urine)
cell disease (psychomoto
r retardation skeletal deformities)
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Lectins, a specific carbohydrate-binding proteins
mediating cell-cell interactions
Structure of a C-type carbohydrate-binding domain
from an animal lectin
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Lining of lymph-node
lymphocyte
Selectins (a member of C-type lectin) mediate
cell-cell interactions
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• Summary
• 1. Monosaccharides are aldehydes or ketones with
  multiple hydroxyl groups.
• 2. Complex carbohydrates are formed by linkage of
  monosacchrides.
• 3. Carbohydrate can attach to proteins to form
  glycoproteins.
• 4. Lectins are specific carbohydrate-binding
  proteins.

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Selected readings Sharon N and Lis H. 1993.
Carbohydrates in cell recognition. Sci. Am. 268
82-89. Woods RJ. 1995. Three-dimensional
structures of oligosaccharides. Curr. Opin.
Struct. Biol. 5 591-598. Fukuda M and Hindsgaul
O. 2000. Molecular Glycobiology. IRL Press at
oxdord University Press. Berg JM et al.
Biochemistry. 2002. W. H. Freeman and Company.