Chapter 3: The Cellular Basis of Life

Learning Objectives:
After completing this chapter, you should be able to:
 Explain the cell theory

 Identify the different types of organelles, their structure &

functions
 Describe membrane permeability & material transport systems
 Explain types of transport in cells

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 3.1 The Cell Theory
 A cell is the basic structural & functional unit of living organisms
 Activities of cell (s) basic for activity of an organism
 All cells arise from pre-existing cells
 Continuity of life from one generation to another has a cellular basis
 Scheliden & Schwann (father of Modern Biology) – 1838
 Proposed “Cell Theory”
1. All known living things are made up of cells
2.Cell is structural & functional unit of all living things
3.All cells come from pre-existing cells by division
i.e. Spontaneous generation does not exist.
4. The smallest clearly defined unit of life is the cell.
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 The term cell was coined by Rebort Hooke (1600)
Characteristics of cells:
 Contain highly organized molecular and biochemical systems
 Surrounded by membrane
 Used to store information (Control center with DNA)
 Use energy and Capable of movement
 Protoplasm – cell contents in thick fluid
 Organelles – structures for cell function
 Sense environmental changes
 Can duplicate (transfer genetic information to offspring)
 Capable of self-regulation
 Many cannot be seen with the naked eye, etc …
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 Cells come in many shapes and sizes with different duties but …

 All cells use DNA to store information Except RNA viruses

 All cells use RNA to access stored information

 All cells use proteins as catalysts (enzymes) for chemical rxns

 All cells use lipids for membrane components

 All cells use carbohydrates for cell walls and cell membrane (if
present), recognition, and energy generation

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All cells have 3 major parts
1. Cell or plasma membrane: the outer boundary of the cell.

2. Cytoplasm and organelles

 Cytoplasm: intercellular fluid packed with organelles (safe env’t)
 Organelles: small structure in cell that perform specific functions

=> Specialized subunit within a cell that has a specific function

3. Nucleus and genetic material:

 Nucleus: central organelle that control cellular activities
 Genetic material: material that stores genetic information

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3.2 Cell Organelles

 Cell divided in 2: Eukaryotes & Prokaryotes

 Eukaryotes: organelle is a membrane bound structure

=> Eg., the nucleus is surrounded by a nuclear membrane (True)

 Prokaryotes: organelle is a membrane bound structure

=> Eg., nucleus lack nuclear membrane (no True nucleus)

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3.2 Cell Organelles
 Based on membrane covering: there are two kinds of organelles

1. Membranous organelles

Endoplasmic reticulum (Rough & Smooth), Golgi bodies, nucleus,

mitochondria, chloroplasts, lysosomes, peroxisomes and vacuoles

2. Non-membranous organelles

Ribosomes, centrosomes, cilia & flagella, microtubules, basal

bodies and microfilaments

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 Plant Vs Animal Cells
• All plants & animals are made of cells
• Plant & animal cells have features in common, like: nucleus,
cytoplasm, cell membrane, mitochondria and ribosomes
• Variations: Plants have cell wall, chloroplasts, permanent
vacuole, larger than animal cells, rectangular in shape
 3.3 Structure and Function of Organelles
I. Nucleus
 Oval shaped & largest central structure
 Contains DNA, chromosomes, nucleolus
 DNA directs protein synthesis & serves as a genetic blueprint
during cell replication
 Governs cellular activities (Control)
 3 types of RNA (involved in protein synthesis)
 m-RNA, r-RNA and t-RNA
 The DNA blueprint serves to pass the genetic characteristics to
future generation
 Usually 1/cell & visible with microscope
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 Nucleus….

 The nucleus is surrounded by a nuclear envelope and contains

chromatin and one or more nucleoli
The Nuclear envelope
 Surrounds nuclear material

 Consists of outer and inner membrane

 Perforated at intervals by nuclear pores

 Through this pores most ions and water

soluble molecules to transfer b/n

nucleus and cytoplasm
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 Nucleus….

Chromatin (Chromosomes)
 The term chromatin means "colored material" this material is easily
stained for viewing with microscope
 Composed of coils DNA bound to basic protein called Histones
 DNA is so long but coiled & packed in small size with Histones
 Set number per species (i.e. 23 pairs for human)

Nucleoli
 Nucleus (Nuclei) of most cells contain one or more lightly stained
structures called Nucleolus (nucleoli)
 Contains large amounts of RNA and protein
 Actively engage in synthesizing of ribosomes
 Enlarged when a cell is actively synthesizing proteins
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II. Cytoplasm
Cytoplasm is the gel-like fluid inside the cell
 Viscous fluid containing organelles (cytosol + Organelles)
It is the medium for chemical reaction
Provides platform for organelles to function within the cell
 Cell expansion, growth & replication
 The organelles dispersed
within a complex jelly –like
marrow called the ‘Cytosol’

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III. Endoplasmic reticulum (ER)
 The ER is a fluid-filled membrane system
 Network of interconnected membranes
 The ER is one continuous organelle with many communicating
channels (cell-connected with the nucleus )
 The two types = smooth and rough ER
 They differ in structure and function

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 Endoplasmic reticulum
Rough Endoplasmic Reticulum (rER)
 The outer surface of the rER contains dark particles = ribosomes

 The rER with ribosomes produces & releases a variety of proteins

Smooth Endoplasmic Reticulum (sER)

 Have no ribosomes, so it is called ‘smooth’

 Does not produce proteins

 sER serves in packaging & discharging site for protein molecules
 Used as protein/molecule 'transport vesicles’ to the Golgi complex
 Has enzymes that help build molecules for making
 Carbohydrates & Lipids
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 Endoplasmic reticulum
Smooth Endoplasmic Reticulum (SER)…
 Some specialized cells have an extensive sER & has additional
functions as follows:
 The sER of the liver & kidney cells are responsible for the
detoxification and inactivation of drugs
 Enzymes within the sER can inactivate or destroy a variety of
chemicals including alcohol, pesticides, and carcinogens
 In skeletal muscle cells, sER stores Ca2+ to be released for muscle
contraction
 The sER is well developed in cells specialized in lipid metabolism
 The membrane wall of the sER contains enzymes for synthesis of
lipids
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IV. Golgi Complex (Golgi Apparatus)
 It contains sets of flattened, curved, membrane- enclosed sacs

 Golgi Complex performs the following important functions:

 Processing the raw material into finished products (modify

molecules)
=> “raw” proteins from the ER are modified by attaching the sugar
 Package, Sorting & directing finished product to their function site

 Store molecules come in vesicles

 Vesicles fuse with Golgi membrane & combine with plasma
membrane to secrete contents
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Golgi Complex …

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V. Lysosomes
 Lysosomes serve as the intracellular “digestive system”
 It contain powerful hydrolytic enzymes capable of digesting and
removing unwanted cellular debris and foreign materials
 Extrinsic material ingested by process of endocytosis
 If it is fluid is = Pinocytosis & solid = Phagocytosis
 If a specific molecule may bind to surface receptor, the process
is called receptor-mediated endocytosis
 Functions
 Aid in cell renewal
 Break down old cell parts
 Digests invaders
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 Lysosomes…

 In phagocytosis (eg.WBCs) have role in body’s defense mechanism

 Autophagy: the process by which worn-out organelles are digested

 Human liver cell recycles about half its content every week

 In the lysosomal storage disease (Tay-Sachs disease), inherited

condition & lysosomes are not effective b/se lack specific enzymes

 As a result, harmful waste products accumulate disrupting the

normal function of cells, often with fatal results

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 Lysosomes…

Peroxisome
 It is membrane-enclosed sacs containing oxidative enzymes and
catalase that detoxify various wastes
 Oxidative enzymes need oxygen to remove hydrogen from
specific substance/molecule
 It also contains catalase, and antioxidant enzyme decomposing
hydrogen peroxide into harmless water and oxygen.
 Peroximal disorders disrupt the normal processing of lipids and
can severely disrupt the normal function of the nervous system by
altering the structure of the nerve cell membrane
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VI. Mitochondria
 It is the “power houses”: extract energy from nutrients &
transform it into usable form to energize cell activity
 Break down fuel molecules (glucose & fatty acids)-cellular respiration

 Rod or oval shaped and enclosed by a double membrane

 Two spaces within the mitochondria (Matrix & Cristae)
 Matrix
oLocation of mitochondrial DNA
oSite of mitochondrial protein synthesis
 Cristae: Inner membrane folded into inward projections & site of
energy generation
o Energy-producing chemical reactions take place on cristae
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 Mitochondria….
 The high energy phosphate bonds of ATP (adenosine with 3
phosphate groups)
 ATP is the universal energy carrier of the body
 Cells use ATP as energy source for running the cellular machine
 Splitting of bond b/n 2nd & 3rd phosphate yield energy

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 Mitochondria….
Mitochondria are unusual organelles :
 The site of oxygen consumption within cells
 Have their own DNA that is similar to prokaryotic DNA
 Have their own ribosomes that are similar in construction to
prokaryotic ribosomes
 Have the ability to replicate themselves even the cell not
undergoing cell division
 Replicate by binary fission - similar to prokaryotic cell division

 Synthesize many, but not all, of their own proteins

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VII. Chloroplasts
 Chloroplasts are useful organelles among plastids as they highly
participate in the process of photosynthesis

 Located in outer surface of the cell to receive enough solar light

 Chloroplasts are green colored pigment = Chlorophyll pigments

found in its internal parts

 The important characteristics of plant is its ability to make their own

food and converting light energy in to chemical energy
 Site of food (glucose) production
 Double membranous
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VIII. Vacuoles
 Essentially larger vesicles, and they are formed by the joining
together of many vesicles
 They are membrane bound organelles that have no specific shape
 Storage sacs and contains Water, Food & wastes
 It contain water with different
compounds within it
 In plant cells they are important in
maintaining turgor pressure

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IX. Cytoskeleton
 Complex protein network that act as the “bone & muscle” of the cell
 Intracellular scaffoldings supports & organizes cellular components

 Arrangements & to control their movements

 Provides distinct shape & size (Mechanical support ) to the cell
 Give the shape of a cell and structural support
 Anchor organelles & facilitate their movement

 Also contribute to movements of the cell as a whole

 This network has at least four distinct elements:

Microtubules,
Microfilaments,
Intermediate filaments and micro-tubular lattice 27
 Cytoskeleton…

 Microtubule is the largest of the

group; slender, long, hollow
tubes composed of a globular
protein molecule (6nm diameter)
tubulin
 Microfilaments are the smallest
of the cytoskeleton composed of
protein molecules

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Strictures of cytoskeleton
X. Plasma/Cell Membrane
 It is extremely thin layer of lipids and proteins
 Outermost boundary of living cells & enclosing intracellular
 Mechanical barrier that traps needed molecules within the cell

 Made of phospholipids bilayer & proteins

 It appears as ‘tri-laminar’ layer structure having two dark layers
separated by a light middle layer

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Fig: 3.4. Structure of cell membrane 31
 Plasma/Cell Membrane…
 Plasma membrane are made up of lipids & proteins plus small
amount of carbohydrates
 Phospholipids have a polar charged head (negatively charged
phosphate group) & two non-polar fatty acid tails
 The polar end is hydrophilic (water loving) and the non-polar end
is hydrophobic (water fearing)
 Such two-sided molecule self-assemble into a lipid bilayer, a double
layer of lipid molecules when in contact with water
 Cholesterol provides to the fluidity as well as the stability
 Fluidity of the membrane gives flexibility (cell change its shape)
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 Plasma/Cell Membrane….

 Transport processes are also dependent on the fluidity of the lipid

bilayer
 The membrane proteins are either attached to or inserted within
the lipid bilayer
=> anchored either the outside or inner surface, of lipid bilayer
 Mosaic pattern of the protein embedded in the lipid layer
 Short-chain carbohydrates are bound primarily to membrane
proteins and to a lesser extent to lipids = forming glycoproteins
and glycolipids
 Lipid bilayer forms the basic structure of the membrane; it is a
barrier to passage of water-soluble substances

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 Plasma/Cell Membrane…
Molecules in the membrane have a variety of functions:
 Membrane contains Protein, Carbohydrates & Cholesterol

I. Membrane Carbohydrate: Short-chain carbohydrate on the

outer membrane surface and serves as:
 Recognition of “self” and cell-to-cell interactions
 Cells recognize each other and form tissues
Functions of biological membranes
The phospholipid bilayers provide the basic structure of the
membrane
Used to restrict entry and exit of polar molecules and ion
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 Plasma/Cell Membrane…
II. Membrane proteins: there are d/t proteins with d/t function
 Channel protein: remain open & selectively allow ions & water
 Carrier protein: carrier & transport selectively specific polar
molecule, ion & glucose (undergo structural change)
 Enzymes: membrane proteins/enzymes control specific chemical
reactions on the membrane

 Receptor molecules: proteins have very specific shapes and this

makes them ideal as receptor molecules for chemical signaling

 Maintain cell shape & Function as cell adhesion molecules

 ‘self’ & in cell-to-cell interactions (conjugated with carbohydrate)

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Membrane protein …

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 Plasma/Cell Membrane….

 Glycolipids: branching carbohydrate side chain and are involved

in cell-cell recognition
 Act as a receptor sites for chemical signals
 With glycoproteins they also involved in sticking the correct cell
together in tissues
e.g. sperm recognition of ova

 Cholesterol: acts like a plug, reducing even further the escape or

entry of polar molecules through the membrane
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 3.4 Cellular Diversity
 Cells are very diverse in their size, shape & their internal structure
 This also applies to cells found in the same organism

 Cell Shape: have different shapes due to appropriate function

 e.g skin cells have a shape which is flat and nerve cells have
long extensions

 Cell Size: Most cells are microscopic but some seen with naked eye
 e.g. egg of birds/reptiles and a neuron cell of giraffe, which is 2
meters in length

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c

Various types of animal cells (shape)

3.5 Transport Across the Cell Membranes
 The plasma membrane is selectively permeable membrane

 Lipid-soluble substances can passively diffuse through

 Uncharged/non-polar molecules are readily permeate the membrane

but not charged particle/polar molecules

 The phospholipid bilayer is a good barrier around cells, especially to
water soluble molecules

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 3.5 Transport across the cell membranes…
There are 4 basic mechanisms of material transport
– Diffusion and facilitated diffusion
– Osmosis
– Active transport
– Bulk transport

Two forces are involved in facilitating movement across the plasma

membrane:
1. Forces that do not require the cell to expend energy for movement
– passive force
2. Forces requiring energy (as ATP) to be expended to transport
across the membrane - active force
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 Diffusion
 Diffusion is the net movement of molecules (or ions) from high to

lower concentration

 Such a difference in concentration in molecules b/n two adjacent

areas is chemical / concentration gradient

 Factors influence the rate of diffusion across a membrane

1. Permeability of the membrane
2. Surface area of the membrane
3. Molecular weight of the substance (lighter one diffuses rapidly)
4. Distance through which diffusion must take place
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 Diffusion of Liquids

Fig: 3.7. Diffusion of liquid

 Diffusion of molecules reach an equilibrium (there is no net
movement of molecules from either side)

Movement along electrical gradient

 Movement of charged particles is also affected by their electrical
gradient 43

The cations tend to move towards negatively charged area, Whereas

The anions tend to move toward the positively charged areas
Concentration difference (A) and direction of diffusion (B)

Diffusion of lipid soluble molecules 44

Carrier-Mediated Transport
 All carrier proteins span the thickness of the plasma membrane
and able to undergo reversible changes in shape so that specific
binding site can alternately be exposed at either side of the
membrane
This transport displays three characteristics:
1. Specificity: each cell possesses protein specified to transport a
specific substance or few closely-related chemical compounds
 Amino acid cannot bind to glucose carrier, but similar amino
acids may use the same carrier
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 Carrier- Mediated Transport…..
2. Saturation: Limited number of carrier site are available within a
particular plasma membrane for a specific molecule
 This limit is known as transport maximum (Tm)
 The substance’s rates of transport across the membrane are directly
related to its concentration
 When the Tm is reached, the carrier is saturated, and the rate of
transport is maximum
 Further increasing the concentration is not increase the rate of
transport
3. Competition: Several closely related compounds may compete for
ride across the plasma membrane on the same carrier
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Facilitated Diffusion

 It uses a carrier protein to facilitate the transfer of a particular

substance across the membrane ''downhill'' from higher to lower

concentration (passive transport)

Osmosis
 Osmosis is the net diffusion of water down its own concentration
gradient
 From area of higher water concentration (low solute) to the area of
lower water concentration (high solute)

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Diffusion of water molecules

Diffusion of water molecules 48

Active transport
 Active transport is energy consuming and transport molecules
against its natural tendency (Concentration gradient)
 The movement of molecules is in one direction only; unlike
diffusion
 The major ions within the cells and their surrounding are sodium
(Na+), potassium (K+) and chloride (Cl-).
 The cell surface membrane of most cell have (Na+) pump is
coupled with a (K+) pump

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 Active transport ….

 Actively moves K+ ion into inside & Na+ into outside of the cell

 The combined pump is called the sodium pump (Na+- K+ pump)

 The pump is a carrier protein that spans across the membrane from

one side to the other.

 This active transport mechanisms are often called ‘pumps’,

analogous to lift water by pump that need energy to lift water against

the downward pull of gravity

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 Active transport ….

Sodium-Potassium pump
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 Active transport ….
Na+-K+-pump plays three important roles

 It establishes Na+ and K+ concentration gradients across the

plasma membrane of all cells

 It helps regulate cell volume by controlling the concentration of

solutes inside the cell

 The energy used to run the pump also indirectly serves as the

energy source for the co-transport of glucose and amino acids

across the membrane (intestine and kidney cell).

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Crossing mechanisms of molecules through cell membrane

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 Bulk Flow
Exocytocis and Endocytisis

 Vesicular Transport the special cell membrane transport system

selectively transports ions and small polar molecules

 But large polar molecules and even multimolecular material may leave or

enter the cell, such as hormone secretion or ingestion of invading microbe

by leukocytes

 This process of transport into or out of the cell in a membrane-enclosed

vesicle is - vesicular transport

 Transport into the cell is termed endocytosis, whereas transport out of the

cell is called exocytosis

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Endocytosis: is an active processes involving the bulk transport of
materials through membranes, in to cells

 It occurs by an in folding or extension of cell surface membrane to

form a vesicle or vacuole

Endocytosis can occur in three ways

 Phagocytosis ("cell eating")
 Pinocytosis ("cell drinking")
 Receptor-mediated endocytosis
 Phagocytosis (cell eating) material taken up by the cell in the solid form
 Pinocytosis (cell drinking) material taken up by the cell in liquid form
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Exocytosis
It is an active processes involving the bulk transport of materials
through membranes (out of cells)
 Exocytosis is the reverse process of endocytosis
Waste materials such as solid and undigested remains removed
from cells
Secretion of enzymes from the pancreas is achieved in this way
Plant cells use exocytosis to export the materials needed to form
cell wall

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Fig: 3.13. Exocytosis
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 CHAPTER 4:

Cellular Metabolism &

Metabolic Disorders

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Objectives

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 Cellular metabolism
 Metabolism: the sum of enzyme-mediate chemical reactions takes
placed in each cell (living organism)
 Extract energy from environments & provides for vital activities
 Assemblage & breakdown of macromolecules

 Transport of Substances across cell membranes

 Transcription & translation of Genetic instructions
 Movement, growth, development, reproduction & maintenance of
cell/body part
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 Cellular metabolism
 The primary functions of metabolism are:
 Acquisition & utilization of energy
 Removal of waste products

 The energy is extracted from nutrients and/or solar energy

 Divided into 2: Anabolism & Catabolism reactions

 Catabolic reactions: convert nutrients to energy

 Energy-yielding rxns by breaking down larger molecules into

smaller molecule

 Degradation of fuel molecules and the production of energy for

cellular function
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 Cellular metabolism
 Anabolic reactions: the synthesis of larger biomolecules

 Energy-requiring rxns that build larger molecules from smaller

molecules
 Use energy produced by catabolism (metabolic pathway)
 Insure the continual flow of energy within an organism

 Metabolic pathway: series of chemical rxns in which the product

of one reaction is the substrate for the next reaction
 Metabolites: reactants & products of both anabolic & catabolic rxns
 Proteins, Carbohydrates, Nucleotides, Lipids, Coenzymes, & cofactors

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 Cellular metabolism
 2 types: hydrophilic (polar) & hydrophobic (nonpolar) metabolites

 Polar metabolites: soluble in water & include most sugars, purines

& pyrimidines, amino acids, phosphorylated compounds & etc.

Are the reactants and products involved in cellular respiration &

Involved in the production of building blocks for synthesis of large

biopolymers such as DNA, RNA, proteins & oligosaccharides

 Nonpolar or hydrophobic metabolites are commonly lipids.

Function in energy storage, membrane structure, & signal

transduction
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 4.2. Enzymes & their role in metabolism
What Are Enzymes?
 Most enzymes are Proteins (tertiary & quaternary structures)
 Biological Catalyst to accelerates a biochemical reaction in a cell
 By lowering activation energy &
 Molecular rearrangements for weakening of bonds
 Activation Energy is needed to convert potential energy into kinetic
energy
 Not permanently changed (not consumed) in the process
 Are specific in catalyze & Reusable (specific to the substrate)
 End in –ase (Sucrase, Lactase, Maltase)
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 Enzyme …
 Based on chemical nature divided in 2: Simple & Holo enzyme
1.Simple enzyme: made of only protein molecules
=> Eg., pepsin, trypsin
2. Holo enzyme (Conjugate Enzymes): made of protein groups &
non-protein component
 The protein component is called apo-enzyme
 „The non-protein component is called a co-factor
 If the cofactor is an organic compound it is called a coenzyme
 If it is inorganic groups (metallic ions) called activator
=> Fe 2+, Mn2+, Zn2+ ions
 If the cofactor is bound so tightly to the apo-enzyme & is difficult
to remove without damaging the enzyme called a prosthetic
group 67
 Enzyme …
COENZYMES-
 Coenzymes are derivatives of vitamins without which the enzyme
cannot exhibit any reaction & loosely attached to the enzyme
 One molecule of coenzyme is able to convert a large number of
substrate molecules with the help of enzyme„
 Coenzyme accepts a particular group removed from the substrate or
donates a particular group to the substrate „
 Coenzymes are called co-substrate because the changes that take
place in substrates are complimentary to the changes in coenzymes
 „The coenzyme may participate in forming an intermediate enzyme-
substrate complex => Example: NAD, FAD, Coenzyme A
68
 Cont…

Metal ions in enzymes

 Many enzymes require metal ions for their activity

=> Eg.
 Metal-activated enzymes-form only loose & easily dissociable
complexes with the metal & easily release the metal without
denaturation
 Metallo-enzymes: hold the metal tightly on the molecule and do
not release it even during extensive purification

=> E.g., Iron of hemoglobin or cytochrome

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 Cont…
Properties of Enzymes
 Active site: the active site binds the substrate, forming an enzyme-
substrate (ES) complex
 ES is converted to enzyme-product (EP); which subsequently
dissociates to enzyme and product

 Enzyme turnover number: refers to the amount of substrate converted

per unit time
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Isoenzymes (Isozymes)
These are enzymes having similar catalytic activity,
Act on the same substrate and produces the same product but
originated at different site
Example: LDH (Lactate dehydrogenase) exists in five different
forms each having four polypeptide chains. H= Heart and
M=Muscle.

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 Cont’d…
Classification of Enzymes on the basis of the reactions they catalyze

72
Cont’d…

73
 Major classes of Enzymes

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Factors Affecting Enzyme Activity
Physical and chemical factors are affecting the enzyme activity.
These include
 Temperature, pH, Substrate concentration, Enzyme concentration,
Enzyme inhibitors, Cofactors & Coenzymes
Temperature
 Optimal temper. (To) – for the maximal catalytic power of enzyme
 35 ~ 40C for warm blood species.
 Higher T will denature the enzyme.
 Breaking bonds within the enzyme will cause the active site to
change shape
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 Factors Affecting Enzyme Activity …
pH - Acidity & Basicity
 Optimal pH - the enzyme has the maximal catalytic power
 pH 7.0 (suitable for most enzymes)
 Eg., pepsin = 1.8 & trypsin = 7.8
 H+ and OH- ions are charged & therefore interfere with H &
ionic bonds that hold together & change the shape of the enzyme
Concentration of substrate
 An increase in the substrate concentration increases the enzyme
activity till a maximum is reached.
 Further increase in substrate concentration does not increase rate of
reaction - The active Sites become saturated
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 Factors Affecting Enzyme Activity …
Enzyme Concentration
 The rate of the reaction is directly proportional to enzyme
concentration at all substrate concentration
 Increasing enzyme concentration will increase the rate of reaction -
only up to a certain concentration (not the limiting factor)

Cofactors:
 Inorganic substances (zinc, iron, copper) are sometimes need for
proper enzymatic activity
 Non-protein helpers can bond to the active site of enzymes to help
in reactions Eg., Iron in hemoglobin in order for it to pick up O
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 Factors Affecting Enzyme Activity …
Coenzymes: Organic molecules that act as cofactors & help enzymes
 Eg., vitamins

Enzyme inhibitors: inhibit enzyme activities in 2 ways

I. Irreversible inhibition: change/modify an enzyme & inhibit the
activity - not be reversed
II. Reversible inhibition: Competitive & Noncompetitive inhibitors
a.Competitive inhibitors: are chemicals that resemble an enzyme’s
normal substrate and compete with it for the active site

b. Noncompetitive inhibitors: bind to another part of the enzyme &

cause change in shape, then in turn alters the active site shape
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 Factors Affecting Enzyme Activity …
Control of Metabolism
 Is necessary if life is to function
 Controlled by switching enzyme activity "off" or "on” or
separating the enzymes in time or space
Types of Control
1. Switching on or off the genes that encode for specific enzyme
production
2. Allosteric sites
3. Feedback inhibition
4. Cooperativity
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 Factors Affecting Enzyme Activity …

Allosteric Regulation
 The control of an enzyme complex by the binding of a regulatory
molecule
 Regulatory molecule may stimulate or inhibit the enzyme complex.
 Allosteric site is a specific receptor site on some part of the enzyme
molecule away from the active site
 When activated, this site changes the shape of the enzyme to inhibit
it or to stimulate it

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 Cont’d…

Feedback Inhibition
 When a metabolic pathway is switched off by its end-product.
 End-product usually inhibits an enzyme earlier in the pathway.
 Prevents the cell from wasting chemical resources
81
 Substrate Binding and Enzyme Action
 The first step in a enzyme catalyzed reaction is the formation of
the enzyme-substrate complex.
E + S = ES = E + P
 The substrate binds to the site of enzyme called active site
Active site consists of a substrate binding site & the catalytic site
 The active site is usually a cleft or pocket created by the unique
tertiary structure of the enzyme protein
 Enzyme specificity is due to specificity of substrate binding driven
by substrate and enzyme 3D structure
 The ES complex is stabilized in the transition state by non-
covalent interactions b/n substrate & the active site.
82
 Enzymatic reaction steps

1. Substrate approaches active site

2. Enzyme-substrate complex forms
3. Substrate transformed into products
4. Products released
5. Enzyme recycled
  MECHANISM OF ACTION OF ENZYMES

A. Lock & Key model: the active site of the enzyme is

complementary in shape to that of its substrate, i.e. the shape of the
enzyme molecule and the substrate molecule should fit each other
like a lock and Key

12/26/2022 84
B. Induced fit model (1958 by Daniel Koshland)
* Enzyme structure is flexible, not rigid.
* Enzyme & substrate adjust the shape of the active site to bind substrate
* The range of substrate specificity increases

* A different substrate could not induce these structural changes and no

catalysis would occur

12/26/2022 85
 4.3 Bioenergetics and Biosynthesis
4.3.1. Cellular respiration
 Energy is obtained by breaking down organic molecules
(catabolism) during cellular respiration.
 This catabolic process can be divided into 3 phases.

 Phase I - Breakdown of large complex biomolecules like

polysaccharides, proteins and lipids into their respective building
blocks (hydrolysis)
 The chemical reactions occurring during this stage do not release
much energy – i.e., only 2 net ATP
 Cellular respiration …
 Phase II - These building blocks are usually oxidized to a common
intermediate, acetyl – CoA, it is called Transition phase
 Additionally, pyruvate or other citric acid cycle intermediates may
also be formed (in glycolysis and other pathways)
 Phase III – This consists of the citric acid cycle (i.e. oxidation of
acetyl - CoA to CO2,
 Formation of NADH and FADH2, which are utilized electron
transport and oxidative phosphorylation
 Energy released by electron transport to O2 is coupled to ATP
synthesis
 This cycle is responsible for the release of much energy (TCA cycle
and ETC)
 Molecular structure of ATP
 Adenosine triphosphate (ATP) is a nucleoside triphosphate used
in cells as a coenzyme.
 Often called the "molecular unit of currency" of intracellular
energy transfer.
 ATP transports chemical energy within cells for metabolism.
 It is one of the end products of photophosphorylation, cellular
respiration, and fermentation
 Used by enzymes & structural proteins in many cellular processes,
including biosynthetic reactions, motility, & cell division
 Molecular structure of ATP …

 Substrate level phosphorylation, oxidative phosphorylation in cellular

respiration, and photophosphorylation in photosynthesis are three major
mechanisms of ATP biosynthesis.
 Metabolic processes that use ATP as an energy source convert it back
into its precursors – i.e., ADP
 ATP is therefore continuously recycled in organisms
 One molecule of ATP contains 3 phosphate groups, and it is produced by
a wide variety of enzymes, including ATP synthase, from adenosine
diphosphate (ADP) or adenosine monophosphate (AMP) and various
phosphate group donors.
 Molecular structure of ATP …

ATP consists of adenine, ribose & phosphate chain

4.3.1.1 Anaerobic respiration
• Anaerobic respiration uses electron acceptors other than oxygen
• Anaerobic metabolic processes do not require oxygen.
Glycolysis
 Glycolysis (from glycose, an older term for glucose + -lysis
degradation) is the metabolic pathway that converts glucose
(C6H12O6) into pyruvate (CH3COCOO−) + H+

 The free energy released in this process is used to form the high-
energy compounds ATP & NADH (reduced nicotinamide adenine
dinucleotide, NAD+)
 Glycolysis …
 Glycolysis does not require or consume oxygen.
 The most ancient known metabolic pathways b/se it occurs in
both aerobic & anaerobic pathways
 It occurs in the cytosol of the cell

 The entire glycolysis pathway can be separated into two phases:

1. The Preparatory Phase (investment phase): ATP is consumed

 The first five steps are regarded as the preparatory (investment)
phase, since they consume energy (i.e., 2 ATP) to convert the
glucose into two three-carbon sugar phosphates (G3P).
 Glycolysis …
2. The Pay Off Phase – in which ATP is produced.
 Characterized by a net gain of the energy-rich molecules ATP and
NADH.
 This yields 2 NADH molecules and 4 ATP molecules, leading to a
net gain of 2 NADH molecules and 2 ATP molecules from the
glycolytic pathway per glucose.
 Substrate-level phosphorylation is the mechanism to produce
ATP during glycolysis
 Substrate-level phosphorylation includes both glycolysis & Krebs
cycle and produces 4 ATP (net 2 ATP from each)
 Glycolysis …
Biochemical logic for the presence of regulatory steps
 The existence of more than one point of regulation indicates
that intermediates between those points enter and leave the
glycolysis pathway by other processes.
 For example, in the first regulated step, hexokinase converts
glucose into glucose-6-phosphate. Instead of continuing
through the glycolysis pathway, this intermediate can be
converted into glucose storage molecules, such as glycogen
or starch.
Glycolysis involves ten enzymatic reactions as described below
Glycolysis (with clear chemical formula)

96
Summary of glycolysis

97
 4.3.1.2 TCA cycle and ETC
Aerobic respiration
• One fate of pyruvate is that it enters to TCA (tricarboxylic acid cycle)
cycle for complete oxidation. But there are intermediate processes:
Oxidation of Pyruvate to form Acetyl CoA for Entry Into the Krebs
Cycle
• 2 NADH's are generated (1 per pyruvate)
• 2 CO2 are released (1 per pyruvate)
The Krebs Cycle (citric acid cycle, TCA cycle)
 It is central pathway of aerobic metabolism & serves two purposes:
=> bioenergetics & biosynthesis
1.Bioenergetics: The cycle carries out complex degradation of
acetyl group in acetyl - CoA to CO2, resulting in release of energy
(ATP or GTP) and reducing power (NADH and FADH2)
2.Biosynthesis: It supplies precursors for several biosynthetic
pathways of amino acids, pyrimidines, purines etc
Example:- α-ketoglutarate and oxaloacetate are used for synthesis of
a number of amino acids like glutamic acid, asparatic acid etc
 Acetyl - CoA is the starting material for fatty acid biosynthesis.
 • 6 NADH's are generated (3
per Acetyl CoA that enters)
• 2 FADH2 is generated (1 per
Acetyl CoA that enters)
• 2 ATP are generated (1 per
Acetyl CoA that enters)
• 4 CO2's are released (2 per
Acetyl CoA that enters)

Therefore, the total numbers of

molecules generated in the
Oxidation of Pyruvate and the
Krebs Cycle is: 8 NADH, 2
FADH2, 2 ATP and 6 CO2
 Summary of TCA (Krebs) cycle

12/26/2022 101
 7.3.2 Electron transport chain
• In aerobic respiration, electron transport is the final step in the
break-down of glucose.
• It also is the point at which most of the ATP is produced
• High-energy electrons & hydrogen ions from NADH & FADH2
produced in the glycolysis & Krebs cycle are used to convert ADP
to ATP.

The maximum net Energy Production from Aerobic Respiration is 36-38.

 Overview of chemiosmotic theory(ETC)

12/26/2022 103
 Biosynthesis
 Biosynthesis is a multi-step, enzyme-catalyzed process where substrates
are converted into more complex products in living organisms.
 In biosynthesis, simple compounds are modified, converted into other
compounds, or joined together to form macromolecules.
 This process often consists of metabolic pathways.
 Some of these biosynthetic pathways are located within a single cellular
organelle, while others involve enzymes that are located within multiple
cellular organelles.

 Examples of these biosynthetic pathways include the production of

lipid membrane components and nucleotide.
104
 Cont…
 The prerequisite elements for biosynthesis include: precursor
compounds, chemical energy (e.g. ATP), and catalytic enzymes
which may require coenzymes (e.g.NADH, NADPH).
 These elements create monomers, the building blocks for
macromolecules.
 Some important biological macromolecules include: proteins,
which are composed of amino acid monomers joined via peptide
bonds, and
 DNA molecules, which are composed of nucleotides joined via
phosphodiester bonds.

105
 Requirements of Biosynthesis
I. Photosynthesis
 Energy is transformed all around us every day.
 Similarly, some autotrophs convert light energy into chemical
energy through photosynthesis.
The importance of photosynthesis
 The processes of all organisms, from bacteria to humans require
energy and to get this energy, many organisms access stored
energy by eating food.
 Carnivores eat other animals and herbivores eat plants. But where
does the stored energy in food originate?
106
 Cont’d…

 Photosynthesis is essential to all life on earth.

 It is the only biological process that captures energy from outer space
(sunlight) and converts it into chemical energy
 The chemical energy is formed in the form of Glyceraldehyde-3-
phosphate (G3P)
 which in turn can be made into sugars and other organic
compounds such as proteins, lipids, and nucleic acids
 ATP & NADPH are the result of light reaction whereas G3P is the
result of Dark-reaction (Calvin cycle)
 Plants use these compounds in all of their metabolic processes.
107
 The process of photosynthesis
 During photosynthesis, molecules in leaves capture sunlight and
energize electrons, which are then stored in the covalent bonds of
carbohydrate molecules.
 That energy within those covalent bonds will be released when they
are broken during cell respiration.
 Photoautotrophs
 Are organisms (plants, algae, and some bacteria) which have a
capability of performing photosynthesis and they use light to
manufacture their own food.
108
 Cont’d…

 Heterotrophs: are organisms, such as animals, fungi, and most other

bacteria, they must rely on the sugars produced by photosynthetic
organisms for their energy needs.
 Chemoautotrophs: are very interesting group of bacteria synthesize
sugars, not by using sunlight's energy, but by extracting energy from
inorganic chemical compounds.
 The importance of photosynthesis is not just that it can capture
sunlight's energy, rather it converts light energy to chemical energy
 All organisms in this world survive with the energy supply of
photosynthesis organisms
109
 Cont’d…
Other variant of photosynthesis
 Commonly known photosynthetic processes is the one known as
oxygenic photosynthesis.
 The other type is termed as anoxygenic photosynthesis.
 The general principles of anoxygenic and oxygenic photosynthesis
are very similar,
 But oxygenic photosynthesis is the most common and is seen in
plants, algae and cyanobacteria.
 During oxygenic photosynthesis, light energy transfers electrons
from H2O to CO2, to produce carbohydrates.
 In this transfer, the CO2 is "reduced," or receives electrons, and the
water becomes "oxidized," or loses electrons. Ultimately, oxygen
is produced along with carbohydrates.
110
 Cont’d…
 On the other hand, anoxygenic photosynthesis uses electron
donors other than water.
 The process typically occurs in bacteria such as purple bacteria
and green sulfur bacteria, which are primarily found in various
aquatic habitats.
The photosynthetic apparatus
 Plastids
 Photosynthetic eukaryotic organisms contain organelles called
plastids in their cytoplasm.
 Plastids generally contain pigments or can store nutrients.
 Colorless & non-pigmented leucoplasts store fats & starch, while
chromoplasts contain carotenoids & chloroplasts contain
chlorophyll.
111
 Cont’d…

 Photosynthesis occurs in the chloroplasts; specifically, in the grana

and stroma regions.
 The grana is the innermost portion of the organelle; a collection of
disc-shaped membranes, stacked into columns like plates.
 The individual discs are called thylakoids. It is here that the
transfer of electrons takes place.
 Chloroplasts are similar to mitochondria, the energy centers of
cells, in that they have their own genome, or collection of genes,
contained within circular DNA
112
Cont’d…

113
 Cont’d…
Pigments
 Pigments are molecules that give color on plants, algae & bacteria
and also responsible for effectively trapping sunlight.
 Pigments of different colors absorb different wavelengths of light.
There are 3 main group of pigments.

1. Chlorophylls
 These green-colored pigments are capable of trapping blue & red
light.
 Chlorophylls have three subtypes, called chlorophyll a,
chlorophyll b and chlorophyll c.
114
 Cont’d…
 There is also a bacterial variant aptly named bacteriochlorophyll,
which absorbs infrared light.
 This pigment is mainly seen in purple & green bacteria, which
perform anoxygenic photosynthesis.

2.Carotenoids: these red, orange or yellow-coloured pigments

absorb bluish-green light. Examples of carotenoids are xanthophyll
(yellow) and carotene (orange) from which carrots get their color.
3.Phycobilins: these red or blue pigments absorb wavelengths of
light that are not as well absorbed by chlorophylls and carotenoids.
They are seen in Cyanobacteria and Red algae
115
 Cont’d…
 Antennae is Pigment molecules are associated with proteins,
which allow them the flexibility to move toward light and toward
one another.
 A large collection of 100 to 5,000 pigment molecules constitutes
antennae. These structures effectively capture light energy from the
sun, in the form of photons.
 Reaction centres: the pigments and proteins, which convert light
energy to chemical energy and begin the process of electron
transfer, are known as reaction centres.
116
 Cont’d…
The photosynthetic process
 The reactions of plant photosynthesis are divided into those that
require the presence of sunlight and those that do not.
 Both types of reactions take place in chloroplasts: light dependent
reactions in the thylakoid and light-independent reactions in the
stroma.
 Light-dependent rxns: When a photon of light hits the reaction
center, a pigment molecule such as chlorophyll releases an electron.
 The released electron manages to escape by traveling through an
electron transport chain, which generates the energy needed to
produce ATP and NADPH.
117
 Cont’d…

 The "electron hole" in the original chlorophyll pigment is filled by

taking an electron from water. As a result, oxygen is released into
the atmosphere.
 Light-independent reactions (also called dark reactions and known
as the Calvin cycle): Light reactions produce ATP and NADPH,
which are the rich energy sources that drive dark reactions.
 Although NADPH and ATP provide cells with large amounts of
energy, these molecules are not stable enough to store chemical
energy for long periods of time.
118
 Cont’d…

 Thus, there is a second phase of photosynthesis called the Calvin

cycle in which energy is stored in organic molecules such as glucose.
 Three chemical reaction steps make up the Calvin cycle:
 Carbon fixation, Reduction and Regeneration

 These reactions use water and catalysts.

 The carbon atoms from carbon dioxide are ''fixed,'' when they are
built into organic molecules that ultimately form three-carbon
sugars. These sugars are then used to make glucose or are recycled to
initiate the Calvin cycle again.
119
Cont’d…

120
121
12/26/2022 122
During Calvin cycle: one of the
G3P molecules leaves the
Calvin cycle and is sent to the
cytoplasm to contribute to the
formation other
macromolecules like glucose,
Sucrose, Starch, cellulose, fatty
acids, Amino acids, etc.

12/26/2022 123
 C3 Plants
• During the Calvin cycle, CO2 is used to build sugars

• C3 plants (soybeans, wheat, rice) only use the Calvin

Cycle to fix CO2

– Given this name because CO2 is initially made into a

three carbon compound

• These plants operate during the day

 Stomata is always open
124
 Alternative Pathways

 The environment in which an organism lives can impact the

organism's ability to carry out photosynthesis.
 Environments in which the amount of water or carbon dioxide
available is insufficient can decrease the ability of a
photosynthetic organism to convert light energy into chemical
energy.
 For example, plants in hot, dry environments are subject to
excessive water loss that can lead to decreased photosynthesis.
 Many plants in extreme climates have altered native
photosynthesis pathways to maximize energy conversion.
125
 Cont..
 Some plants that are found in hot, dry environments have
adaptations that minimize water loss while still allowing
photosynthesis to take place:

 C4 plants & CAM plants

 C4 plants
 They do not immediately enter into the Calvin cycle like C3 plants
 Stomata partially closed during the day

 Have a specialized pathway that captures low levels of CO2 &

build 4 carbon compounds that enter the Calvin cycle
 Examples: sugarcane, corn, crabgrass
126
C4 Plants

127
 CAM Plants
 CAM (crassulacean acid metabolism) plants open stomata at
night and close them during the day

 Have a specialized pathway that takes in CO2 at night and

makes a variety of organic acids
 Then during the day, enzymes break down these organic
acids, releasing CO2 that enters into the Calvin cycle

 Examples: cacti and pineapples

Why is C3 photosynthesis so inefficient?

128
CAM Plants

129
Metabolic disorders, diagnosis & treatments
 Metabolism is the breaking down of food to its simpler
components: proteins, carbohydrates (sugars) and fats
 Metabolic disorders occur when these normal processes become
disrupted
 Disorders in metabolism can be inherited, in which case they are
also known as inborn errors of metabolism, or they may be
acquired during your lifetime.
Inherited metabolic disorders
 They are one cause of metabolic disorders, and occur when a
defective gene causes an enzyme deficiency. 130
 Metabolic disorders …

 These diseases, of which there are many subtypes, are known as

inborn errors of metabolism.

 Metabolic diseases can also occur when the liver or pancreas do not

function properly.

 There are numerous examples of inherited metabolic disorders,

classified based on the type of food-related building block that they

affect, including amino acids, carbohydrates, and fatty acids.

131
 Metabolic disorders …
 Inherited causes of metabolic disorders include:
 Carbohydrate disorders; examples include Diabetes insipidus,
hereditary fructose intolerance, galactosemia, pyruvate metabolism
disorders, von Gierke‟s disease, McArdle disease, Pompes disease,
and Forbes‟ disease.
 Fatty acid oxidation defects; examples include Gaucher‟s disease,
Niemann-Pick disease, Fabry‟s disease, and medium-chain acyl-
coenzyme A dehydrogenase (MCAD) deficiency .
 Amino acid disorders; examples include Tay-Sachs disease,
phenylketonuria, tyrosinemia, maple syrup urine disease, and
homocystinuria. 132
 Metabolic disorders …
Other causes of metabolic disorders
 Metabolic disorders can be due to other factors, such as a
combination of inherited and environmental factors.
 Some of the conditions that can cause metabolic disorders include:
 Alcohol abuse, Diabetes (chronic disease that affects your body's
ability to use sugar for energy)
 Diuretic abuse, Gout (type of arthritis caused by a buildup of uric
acid in the joints)
 Ingestion of poison or toxins, including excessive aspirin,
bicarbonate, alkali, ethylene glycol, or methanol
 Kidney failure, Pneumonia, respiratory failure, or collapsed lung
 Sepsis (life-threatening bacterial blood infection)
133
 Metabolic disorders …
Risk factors of metabolic disorders
 A number of factors increase the risk of developing metabolic
disorders.
 Not all people with risk factors will get metabolic disorders.
 Risk factors for metabolic disorders include:
 certain chronic medical conditions, such as lung or kidney disease
and Diabetes.
 Family history of genetic metabolic disorder
 Age- the risk of metabolic syndrome increases with age.
 Obesity and lack of exercise.
 Hormone imbalance
 Insulin resistance: a situation in which a body cannot use insulin
properly.
134
 Metabolic disorders …
Diagnosis of metabolic disorders
 Metabolic syndrome is more effectively diagnosed by testing
different blood markers (specific markers of insulin resistance),
obesity (especially abdominal obesity), high blood pressure, and
lipid abnormalities.
 Specifically, metabolic syndrome is diagnosed if any three of
the following five markers are present:
 Elevated waist circumference: 40 inches or more for men; 35
inches or more for women
 Elevated triglycerides: 150 mg/dL or higher
135
 Metabolic disorders …
 Reduced high-density lipoprotein (HDL) levels (AKA ''good''
cholesterol): less than 40 mg/dL in men; less than 50 mg/dL in
women
 Elevated blood pressure: 130/85 mm Hg or higher or are
already taking blood pressure medications
 Elevated fasting glucose: 100 mg/dL or higher or are already
taking glucose-lowering medications
 The treatment approach for metabolic disorders depends on the
specific disorder.
136
 Metabolic disorders …
 Inborn errors of metabolism (inherited metabolic disorders) are
often treated with nutritional counselling and support, periodic
assessment, physical therapy, and other supportive care options.
 Multiple treatment options are available for inherited metabolic
disorders and examples include:
 Bone marrow transplantation,
 Enzyme replacement therapy in selected patients,
 Gene therapy in selected patients,
 Medications to reduce symptoms, such as pain or low blood
sugar, mineral supplementation, nutritional counselling, surgery
to relieve pain or symptoms, vitamin supplementation and etc.
137
 Cont’d…
Potential complications of metabolic disorders
 Complications of untreated metabolic disorders can be serious,
even life threatening in some cases.
 The risk of serious complications can be minimized following the
treatment plan designed by health care professional.
 Complications of metabolic disorders include:
 Organ failure/dysfunction,
 seizures and tremors, and

 unconsciousness and coma.

138