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BC2-Week 1-Introduction to Metabolism

The document outlines a biochemistry course focused on metabolism, detailing course learning outcomes, topics covered each week, and assessment methods. It introduces key concepts such as catabolism, anabolism, metabolic pathways, and the regulation of metabolic processes. Additionally, it discusses experimental approaches to studying metabolism, including tracing labeled metabolites and systems biology techniques.

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thuy36030
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11 views55 pages

BC2-Week 1-Introduction to Metabolism

The document outlines a biochemistry course focused on metabolism, detailing course learning outcomes, topics covered each week, and assessment methods. It introduces key concepts such as catabolism, anabolism, metabolic pathways, and the regulation of metabolic processes. Additionally, it discusses experimental approaches to studying metabolism, including tracing labeled metabolites and systems biology techniques.

Uploaded by

thuy36030
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Biochemistry 2

Topic 1:
Introduction to metabolism
Vũ Thanh Ngọc, PhD
Department of Applied Chemistry
School of Biotechnology
HCMC International University
[email protected]
Regulations
 On-time
 Focus
 Pro-active
 NOT hesitate to ask questions
 Self-discipline
Course learning outcomes

CLO1. Understand the reactions, bioenergetics and regulation


of different metabolic pathways

CLO2. Propose the approach to study metabolic pathway,


predict the outcome of metabolic homeostasis disturbance and
solution for certain metabolic abnormality

CLO3. Compose a mini-review, present and discuss about a


topic related to metabolic pathways
Topics Week
1. Introduction to metabolism 1
2. Principles of bioenergetics, glycolysis, 2, 3
gluconeogenesis, pentose phosphate pathways
3. Principle of metabolic regulation, fatty acid 4, 5, 6
catabolism, citric acid cycle, fatty acid oxidation
Presentation 7
4. Amino acid oxidation, urea cycle 8, 9
5. Oxidative phosphorylation, photophosphorylation 10, 11
(Writings due on week 11)
6. Carbohydrate biosynthesis, lipid biosynthesis, 12, 13, 14
biosynthesis of amino acids, nucleotides
Presentation 15
7. Integration of metabolism 15
Assessment

Group discussion/quiz

Seminar writing
Group work, see Guideline for details
Presentation

Mid-term exam
See Exam format for details
Final exam
References

[1] Voet, Voet and Pratt, Fundamentals of Biochemistry,


Third Edition, Wiley, 2008

[2] Lehninger: Principles in Biochemistry, 5th edition, 2008


Introduction to Metabolism
Overview of metabolism
► Definition

► Catabolism and anabolism


► Metabolic pathways
► Types of metabolic reactions
► Metabolic regulation
► Compartmentalization

► Source of metabolic energy, carbon and nitrogen


Experimental approaches to the study of metabolism
Definition of metabolism

Metabolism comprises all chemical reactions that occur within living


organism.
2 parts of metabolism

Metabolism is devided into 2 parts:


 Catabolism (degradation)
 Anabolism (biosynthesis)
2 parts of metabolism

Metabolism

Catabolism Anabolism
(degradation) (biosynthesis)

 Organic nutrient molecules  Small, simple precursors


 Smaller, simpler end products  larger, more complex molecules

 Release energy: ATP, reduced  Require energy: ATP and reduced


electron carriers (NADH, NADPH, electron carriers (NADH, NADPH,
and FADH2) and heat and FADH2)
Energy relationships between catabolism and anabolism

Anabolism Catabolism

Metabolic Energy
Energy released
used pathways

Energy
stored
Examples of catabolism and anabolism

Metabolism

Catabolism Anabolism
(degradation) (biosynthesis)

Examples? Examples?
Overview of catabolism
Metabolic pathways
 Metabolic pathways are series of connected enzymatic reactions that
produce specific products.

 Reactants, intermediates, and products are referred to as metabolites.

Enzyme 1 Enzyme 2 Enzyme 3


A B C D
Reaction 1 Reaction 2 Reaction 3

Precursor Product
Metabolites
Metabolic pathways

Metabolic pathways:
 Linear
 Branched: convergent vs divergent
 Cyclic
3 types of non-linear metabolic pathways

(a)

(b)

Branched or cyclic?
Convergent vs divergent?

(c)
Metabolic pathways

Variation of enzyme and metabolite type in a given cell depends on:


 the identity of the organism
 cell type
 its nutritional status
 its developmental stage
Types of metabolic reactions
2 basic chemical principles:

1 A covalent bond consists of a shared pair of electrons,


and the bond can be broken in 2 general ways:

 Homolytic cleavage

 Heterolytic cleavage

A B
Types of metabolic
reactions

2 mechanisms for cleavage


of a C-C or C-H bond
Types of metabolic reactions
2 basic chemical principles:

2 Many biochemical reactions involve interactions between

nucleophiles and electrophiles


Types of metabolic reactions

Most of the reactions in living cells fall into one of five general categories:

 Oxidations-reductions

 Reactions that make or break carbon–carbon bonds

 Internal rearrangements, isomerizations and eliminations

 Group-transfer reactions

 Free radical reactions


Types of metabolic reactions

Oxidations-reduction reactions
Types of metabolic
reactions
Reactions that make or break
carbon–carbon bonds

Carbon–carbon formation rxns


Types of metabolic reactions
Internal rearrangements, isomerizations and eliminations
Types of metabolic reactions
Group-transfer reactions

Common group transfer:

 Acyl group

 Glycosyl group

 Phosphoryl group
Types of metabolic reactions
Group-transfer reactions

Phosphoryl group transfers play a special role in


metabolic pathways.
Types of metabolic
reactions

Free radical reactions


Metabolic regulation
 Essential to suit the needs of the organism.
 Mechanisms:
 Modulation of enzyme activity
 Allosteric regulation
 Covalent modification
 Up- or downregulation of the amount of enzyme in cells
via induction or repression of their synthesis or degradation
Metabolic regulation
Metabolic pathways are regulated at several levels:
 Within the cells:
 Availability of substrate (1)
 Allosteric regulation (2) by a metabolites or coenzyme
 Outside the cells (multicellular organisms):
Extracellular signal such as growth factors and hormones
 Allosteric regulation (4)
modify enzyme activity
 Covalent modification (5)
 Genetic regulation (6) modify enzyme concentration
Compartmentalization of metabolic pathways

 Metabolic pathways occur in specific cellular locations


 Compartmentalization in the cell allows the adequate spatial localization of
the enzymes of metabolic pathways
 The restriction in distribution and the sequential arrangement of enzymes
in a cell compartment or organelle increases the efficiency at which
chemical transformations can proceed
Compartmentalization of metabolic pathways
Cellular compartments Rough endoplasmic
Cytosol
reticulum

Smooth endoplasmic
Summarize the major reticulum
function of each cellular
Mitochondrion Nucleus
compartment

Peroxisome
(glyoxysome)
Golgi
apparatus Lysosome
Compartmentalization of metabolic pathways
Which compartments
carry out degradative
versus synthetic
processes?

Cytosol

Nucleus

Rough ER

Smooth ER

Mitochondrion

Golgi apparatus

Peroxisome

Lysosome
Compartmentalization of metabolic pathways

In multicellular organisms, compartmentation is carried a step further to the


level of tissues and organs
Ex: mammalian liver
adipose tissue
Source of metabolic energy, carbon and nitrogen

 Many metabolic reactions of metabolism are common to all organisms with


variations due primarily to differences in the sources of the free energy that
supports them.
 Based on the source of metabolic energy, organisms can be divided into
different groups:
 Autotrophs
 Heterotrophs
Source of metabolic energy, carbon and nitrogen

Autotrophs: synthesize all their cellular constituents from simple


inorganic molecules such as H2O, CO2, NH3, and H2S
Chemolithotrophs: oxidize inorganic
compounds such as NH3, H2S, or even Fe2+
Photoautotrophs: utilize photosynthesis

Light energy

photosynthesis
Source of metabolic energy, carbon and nitrogen

Heterotrophs: obtain free energy through the oxidation of


organic compounds (carbohydrates, lipids, and proteins)

 depend on autotrophs
Source of metabolic energy, carbon and nitrogen

Organisms can be classified by the identity of the oxidizing agent for nutrient
breakdown:
• Obligate aerobes (Ex: animals) must use O2
• Obligate anaerobes are poisoned by O2, use oxidizing agents such as
sulfate or nitrate
• Facultative anaerobes (Ex: E. coli) can grow in either the presence or the
absence of O2
Source of metabolic energy, carbon and nitrogen

Animals are obligate aerobic heterotrophs, whose nutrition depends on


a balanced intake of:
• Macronutrients: proteins, carbohydrates, and lipids
• Micronutrients: vitamins + minerals (assist metabolic reaction)
• O2 and water
Source of metabolic energy, carbon and nitrogen

Vitamins

 Vitamins are organic molecules that an animal is unable to synthesize

 Must obtain from diet

 Vitamins can be divided into 2 groups:

 Water-soluble

 Fat-soluble
Source of metabolic energy, carbon and nitrogen

Vitamin A
B1
B2
B3
B5 Water vs fat-soluble?
B6
B7 Which one functions as cofactors or coenzymes?
B9
B12
C
D
E
K
Source of metabolic energy, carbon and nitrogen
Common vitamins and types of reactions/processes in which they participate
Source of metabolic energy, carbon and nitrogen
Minerals participate in metabolic processes in many ways

Ex: Mg2+, Zn2+, Ca2+


Source of metabolic energy, carbon and nitrogen

Carbon source:
 Autotrophs: CO2 from the atmosphere
 Heterotrophs: complex organic molecules
 Carbon and oxygen are cycled between the heterotrophs
and autotrophs with solar energy as the driving force
 Carbon and oxygen cycle
Source of metabolic energy, carbon and nitrogen

Carbon and oxygen cycle


Source of metabolic energy, carbon and nitrogen

Nitrogen source:
 Plants: either ammonia or nitrate
 Vertebrates: amino acids or other organic compounds
 Cyanobacteria and many species of soil bacteria: convert (“fix”)
atmospheric N2 into ammonia
 Other bacteria: oxidize ammonia to nitrites and nitrates or convert
nitrate to N2
 Nitrogen cycle
Source of metabolic energy, carbon and nitrogen

Nitrogen cycle
Experimental approaches to the study of metabolism

Studies of metabolic pathways determine:


Order of metabolic transformations
Enzymatic mechanisms
Regulation
Relationships to metabolic processes in other tissues
Experimental approaches to the study of metabolism
Tracing labelled metabolites
Radioactive isotopes
Fluorescent tracers
Experimental approaches to the study of metabolism
Tracing labelled metabolites
Radioactive isotopes
Fluorescent tracers
Experimental approaches to the study of metabolism

Perturbing the system


Enzyme inhibitors
Natural and engineered mutations
Experimental approaches to the study of metabolism

Systems biology approach


Allow quantitatively describe the properties and dynamics
of biological networks as a whole
Integrate genomic, transcriptomic, proteomic, and
metabolomics information
DNA sequencing, DNA microarrays, proteomic techniques
DNA chips

Differences in yeast gene expression


in the presence and absence of glucose
DNA microarrays

Relative transcriptional activities of the


genes in hepatocellular carcinoma (HCC)
tumors (tumors vs non-tumor liver tissues)
Summary
Overview of metabolism
►Definition
►Catabolism and anabolism
►Metabolic pathways
►Types of metabolic reactions
►Metabolic regulation
►Compartmentalization of metabolic pathways
►Source of metabolic energy, carbon and nitrogen
Summary
Experimental approaches to the study of metabolism
►Tracing labelled metabolites
►Perturbing the system
►Systems biology approach

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