Wei Liu （刘 伟）
Tel：88208357
E-mail: liuwei666@zju.edu.cn
1998:
1999-2001:
2001-2007:
2007-now:
Ph.D.
Assistant Professor
Research fellow,
Professor
Nagoya University, Japan
Aichi Medical, Japan
National Institutes of Health, USA
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
Journal of Cell Science
Hepatology
Journal of Cell Science
Journal of Hepatology
2013
2013
2012
2012
2011
细胞器生物学实验室
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)
Biochemistry
Teaching staff
Wei Liu
Introduction
Bio-molecules
Jin-Biao Zhan
Enzymes
Li-Hong Xu
Metabolism
Yong-Gang Chen
Hormones
DNA replication
Gene expression
Overview of Biochemistry
What Is 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.
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.
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.
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.
Organic Chemistry
Organic Chemistry
Carbon can covalently bond with up
to four other atoms.
Carbon can form immensely diverse
compounds, from simple to complex.
Methane with 1 Carbon atom
DNA with tens of billions of
Carbon atoms
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.
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.
Primary Organic Compounds
You are expected to
learn the structure
and functions of
these organic
compounds:
1.
2.
3.
4.
Carbohydrates
Lipids
Proteins
Nucleic Acids
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.
Monomers
Macromolecule
Carbohydrates
Monomer
Monosaccharide
Lipids
Not always polymers
Proteins
Amino acids
Nucleic acids
Nucleotides
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.
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.
Four major classes of biomolecules
· Carbohydrate
· Proteins
· Nucleic acid
· Lipids
Carbohydrates
Definition: carbohydrates are aldehyde or ketone compounds
with multiple hydroxyl groups.
Sugar: (C-H2O)n
Aldehyde: -CHO
Ketone: C=O
Hydroxyl: -OH
Carbohydrates
Definition: carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl groups.
Function:
Carbohydrates
Definition: carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl groups.
Function:
intermediates.
(1) serves as energy stores, fuel, and metabolic
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.
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.
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.
Monosaccharides are aldehydes or
ketones with multiple hydroxyl groups
The simplest carbohydrates
D-Ketoses containing three, four, five, and six carbon atoms
Asymmetric center
D-Aldoses containing three, four, five, and six carbon atoms
Asymmetric center
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.
The predominant forms of ribose, glucose, fructose, and many
other sugars in solution are not open chains. Rather, the openchain forms of these sugars cyclize into rings.
Where does the ring come from?
An aldehyde can interact with alcohol to form hemiacetal
A ketone can interact with alcohol to form hemiketal
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.
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.
Fructose can form both five-membered frunose
and six-membered pyranose rings
RNA
ribonucleic acid
DNA
deoxyribonucleic acid
Conformation of pyranose ring
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.
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
Carbonhydrates can be modified by the addition of substituents. Such
modified carbohydrates are often expressed on cell surface
Complex carbonhydrate are formed by linkage of monosacchrides
Monosaccharides
O-glycosidic bonds
Oligosaccharides
Sucrose, lactose, and maltose are the common disaccharides
from dietary components
Sucrose, lactose, and maltose are the common disaccharides
from dietary components
sucrase
2 monosaccharides
Glycosidic
bond
enzyme
lactase
Disaccharides
maltase
Electron micrograph of a microvillus
lactose
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.
Carbonhydrates can be attached to ptroteins to form glycoproteins
Carbonhydrates can attach to ptroteins forming glycoproteins
Glycosidic bonds between proteins and carbohydrates
Note
1. Carbohydrates may be linked to proteins through
asparagine (N-linked) or through serine or threonine (Olinked) 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.
Elastase, showing linked carbohydrates on its surface
Protein Glycosylation takes place in the lumen of the ER and the Golgi complex
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.
Bonifacino JS and Glick BS, 2004
1.
Terminal glycosylation: carbohydrate processing in the
Golgi apparatus.
2. Core glycosylation: takes place in the ER.
3.Tremendous structural diversification can occur as a
result of the terminal glycosylation process.
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
Can’t form mannose 6-phosphate
Mistargeting of essential enzymes
(lysosome
blood and urine)
cell disease
(psychomotor retardation + skeletal deformities)
Lectins, a specific carbohydrate-binding
proteins mediating cell-cell interactions
Structure of a C-type carbohydrate-binding domain from an animal lectin
Lining of lymph-node
lymphocyte
Selectins (a member of C-type lectin) mediate cell-cell interactions
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.
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.