jjgj

1. CHAPTER 4
Cellular Metabolism and Metabolic
Disorders
1

2. Learning Objectives:
 By the end of this lecture, the student should be able to :
 Define enzymes and related terms ( active site, apoenzyme,
holoenzyme, prosthetic group, enzyme specificity).
 Describe the structure of enzymes.
 Describe the Mechanism of action of enzymes
 Explain the Classification of enzymes
 Discuss glycolysis, Krebs cycle, ETC
 Explain photosynthesis
 Discuss metabolic disorders

3. Cellular Metabolism and Metabolic Disorders
Cellular metabolism
 Metabolism is thus the sum of chemical reactions that
takes place within each cell of a living organism and
 provides energy for vital processes and synthesizing of
new organic materials.
 Broadly, these reactions can be divided into two
◦ Anabolic reactions: forming bonds between molecules
 dehydration synthesis
 synthesis
◦ Catabolic reactions: breaking bonds between molecules
 hydrolysis
 digestion
 The rate of these metabolic reactions is controlled by enzymes
3

4. Enzymes and their role in metabolism
What Are Enzymes? & What are Properties of
enzymes?
 Enzyme, in Greek means in living (en= in, zyme=
living)
 They are proteins-most enzymes are proteins; Exception
– Catalytic RNA molecules (Ribozymes)
 Enzyme as biological catalyst: they speed up a
reaction by lowering the activation energy
 As a catalyst, the quantities and the qualities of the
enzymes do not change after reaction
 Enzymes are specific, each enzyme usually catalyses
only one reaction
 A small amount of enzyme is enough and can bring
about a change in a large amount of its substrate
 Enzymes are generally named according to the reaction
they catalyze or by suffixing “ase” after the name of
substrate
 E.g. Maltase – helps break down the disaccharide maltose
 Lactase – helps break down the disaccharide lactose 4

5. Why do enzymes speed up
reactions?
 Enzymes speed up reactions by lowering the activation energy (Ea) of a
reaction. The activation energy is the energy needed to start a reaction.
 Different reactions have different activation energies.
reaction (time)
energy
(kJ)
Ea with enzyme
Ea without enzyme

6. Structure and nature of enzymes
 Protein enzymes are classified into 2 types: simple and complex
 1- Simple Protein enzymes: It is made up of only protein molecules not bound to any
non proteins. Example: Pancreatic Ribonuclease.
 2- Complex (conjugated) Protein: formed of protein part and non protein part.
 Apoenzyme or Apoprotein: protein part
 Cofactor: is a non-protein chemical compound that is bound (either tightly or loosely)
to an enzyme and is required for catalysis.
 Enzyme cofactors may be a metal ion (Mg2+ , Ca2+, etc.) or an organic molecule
(coenzyme, are derived from vitamins)
 If the non-protein part (cofactor) is a metal ion such as Cu2+, Fe3+, Zn2+, Mg2+
etc., it is called Activators/metalloenzymes
 If the non protein part(cofactor) are small organic molecules, such as NAD+ and
FAD+ is known as coenzymes
 Coenzymes that are permanently associated with an enzyme known as
prosthetic groups e.g. FAD
 Coenzymes that only temporarily associate with an enzyme known as
cosubstrates e.g. NAD
6

7. Structures of proteins
7
Apoenzyme (inactive) + Cofactor/coenzyme = Holoenzyme (active)

8. Structure of enzymes
Enzymes
Complex/conjugated or holoenzymes
(protein part and non protein part –
cofactor)
Simple (only protein)
Example: Pancreatic
Ribonuclease.
Apoenzyme (protein
part)
Cofactor
Essential ions Coenzyme
Depending on the presence and absence of a non
protein component with the enzyme
Activator
ions/loosely
bounded
Metal ions/
metalloenzymes/
tightly bounded
Ca++
K+
Mg++
Mn++
zinc
copper
cobalt
Cosubstrates/
loosely
bounded
Prosthetic
groups/ tightly
bounded
ATP
NAD+/NADP+
CoA *
ubiquinone *
FMN
FAD
Biotin *
Lipoic acid/
lipoamide

9. Classification of Enzyme:
 Enzyme are classified into six classes and they are :
1. Oxidoreductases: Involved in oxidation-reduction reactions Examples:
Dehydrogenase (Alcohol Dehydrogenase), Oxidase (Cytochrome Oxidase) and
Peroxidase (Glutathione Peroxidase)
2. Transferases: Transfer functional groups from one substrate to another Examples:
Transaminases (transfer aminogroup), Tyrosine Kinases (transfer Phosphate group)
A-X + B ↔ BX +A
AH2 +B → A+ BH2
This enzyme catalyses the transfer of amino group from
glutamic acid to oxaloacetic acid
Hexokinases
This enzyme oxidizes ethanol into acetaldehyde.
It requires the coenzyme NAD+ (Niacinamide
Adenine Dinucleotide) which gets reduced to
NADH.

10. Classification of Enzyme:
3. Hydrolases:
 Catalyze hydrolytic reactions.
 Bring hydrolysis of various compounds
 Example: lipases, esterases, Amylases, peptidases/proteases, etc.
4. Lyases : These enzymes catalyze the addition or elimination of groups
like H2O, CO2, and NH3 etc. without hydrolysis, product has double bond.
Examples: aldolase, decarboxylase
10
A-X + H2O ↔ X-OH +A-H

11. 5. Isomerases: Catalyzes isomerization reactions (Involved in molecular
rearrangements). Examples: glucose phosphate isomerase, Alanine
racemase, Triosephosphate isomerase, etc.
6. Ligases: These enzymes catalyze the synthetic reactions. They link
two substrates together with the utilization of ATP or GTP. Ex:
Synthetases, Carboxylases
11
Classification of Enzyme:
A→A’
A+ B → A-B (joining of A &B)
ATP → ADP+iP
Pyruvate carboxylase

12. Mechanism of action of enzyme: How do
enzymes Work?
 Substrate- reactant which binds to enzyme/ the substance that
undergoes a chemical change by an enzyme
 product - the molecule obtained as a result of the enzyme’s
action/end result of the reaction
 Active site-the location on an enzyme where a substrate is
bound and catalysis occurs
 Active sites generally occupy less than 5% of the total surface
area of enzyme.
12

13. Mechanism of action of enzyme: How do enzymes
Work?
 Enzymes works following the following simple steps
 Step 1: Enzyme (E) molecule first combine with the
substrate (S) to form transient enzymesubstrate complex
(ES).
 Step 2: Then conversion of the substrate (S) to product (P)
occur.
ES ⇆ EP/ Enzyme product complex
 Step 3: At last product (P) release from the enzyme (E).
EP ⇄ E + P
13
E + S ⇄ ES
Enzyme Substrate Complex

14.  There are few of hypotheses for the mechanism of enzyme-
substrate complex, including
 Proposed by Emil Fischer in 1894.
 The active site on the surface of the enzymes, with its shape
complementary to that of the substrate.
 the active site has a rigid shape
 The enzyme acts as a key, while substrate act as the lock.
 This is an older model, however, and does not work for all
enzymes
14
Mechanism of action of enzyme: How do enzymes
Work?

15.  Daniel Koshland suggested this model in 1958, as a modification
to the lock and key model.
 When an enzyme combines with a substrate, its active site/enzyme
undergoes certain conformation change in the structure to make
the fit more precise.
 In the induced-fit model of enzyme action:
 the active site is flexible, not rigid
 the shapes of the enzyme, active site, and substrate adjust to
maximize the fit, which improves catalysis
 This model is more consistent with a wider range of enzymes
15
Mechanism of action of enzyme: How do enzymes
Work?

16. Factors affecting Enzyme activities: reading
assignment
 What Affects Enzyme Activity?
 The activities of enzyme may affect by the following factors:
Environmental Conditions
Cofactors and Coenzymes
Enzyme Inhibitors
A. Environmental Conditions
1. Concentration of the enzyme
16
 When other factor remain
constant, and there is an
abundant of substrates, the rate
of reaction is directly
proportional to the amount of
enzyme.

17. 2. Concentration of the substrate
 When other factor remain constant, for a
given amount of enzyme, the rate of reaction
increases with increasing substrate
concentration up to a point, called the point
of saturation
 Above the point, any further increase in
substrate concentration produces no
significant change in reaction rate, i.e. the
rate of reaction reaches a plateau
 This is because the active sites of the
enzyme molecules at any given moment are
virtually saturated with substrate, i.e. they are
all in use.
17
Factors affecting Enzyme activities

18. 3. pH value
 Each type of enzyme has a particular pH
value at which its catalytic action is the
highest.
 This pH value is the optimum pH of the
enzyme.
 Most enzyme has an optimum pH around
pH 7.
 The optimum pH of an enzyme is correlate
with the location of its activity.
 The optimum pH varies for each enzyme.
 Maltase – pH 7.0 (in the small intestine pH 6 - 8)
 pepsin – pH 1.8 (in the stomach pH 1.5 - 3.5)
 trypsin – pH 8.5 (in the pancrease pH 8.6)
 Animal amylase – pH 6.2 - 7.0 (in the saliva pH5
- 8)
18
Factors affecting Enzyme activities

19.  As temperature increase, the
enzyme catalytic rate increase until
the optimum temperature is
reached.
 Then the enzyme catalytic rate
decreases as the structure of the
enzyme starts to break down under
high temperature.
 optimum temperature for human
enzyme is usually around human
body temperature 37.5 oC.
 The activity of enzyme is generally
inhibited at 40oC and becomes
denature
 The process of protein loses its
structure is called denaturation.
 Denaturation is (generally)
permanent
19
Factors affecting Enzyme activities

20. B. Cofactors and Coenzymes
 Inorganic substances (zinc, iron) and vitamins (respectively) are sometimes need for proper
enzymatic activity.
 Example: Iron must be present in the quaternary structure - hemoglobin in order for it to pick up
oxygen.
C. Inhibitors
 Enzyme inhibitors are substances which alter the catalytic action of the enzyme and consequently
slow down, or in some cases, stop catalysis
 Many drugs and poisons are inhibitors of enzymes in the nervous system.
 There are two main types of inhibitors: irreversible inhibitors, and reversible inhibitors
1. Irreversible inhibitors bind strongly to enzymes, usually by a covalent bond, permanently altering the
structure of the enzyme molecule and inactivating it. For example: Poisonous compounds (e.g. cyanide
and heavy metal ions (e.g. arsenic, lead , mercury ) may kill an organism when ingested
2. Reversible inhibitors bind to enzymes only weakly and the bond that holds them breaks easily
releasing the inhibitor. This allows the enzyme to become active again. There are two main kinds of
reversible inhibitors:
 There are two main kinds of reversible inhibitors: competitive and non-competitive
20
Factors affecting Enzyme activities

21. A. Competitive inhibitors: are chemicals that resemble an enzyme’s
normal substrate and compete with it for the active site.
 Binding of the competitive inhibitor to the active site on the enzyme
prevents binding of the substrate
 Its effect can reversed by increasing substrate concentration
21
Factors affecting Enzyme activities
Enzyme
Competitive inhibitor
Substrate

22. Factors affecting Enzyme activities
B. Noncompetitive (allosteric) inhibitors:
 In this type of inhibition, inhibitor does not compete with the substrate for
the active site of enzyme instead it binds to another site known as allosteric
site.
 Distorts the shape of enzyme, which alters the shape the active site
 prevents the binding of the substrate
 can not have its effect reversed by adding more substrate
22
allosteric site
active site

23. Bioenergetics and biosynthesis
Cellular respiration
 Bioenergetics- Process of converting substrates into energy and
performed at cellular level
 Respiratory substrates are compounds that are oxidized to
release energy during respiration
 This energy is in the form of ATP (called the “energy of currency the
cell”)
 There are two main pathways by which respiration can produce ATP:
 Aerobic pathway (aerobic respiration) – this requires the presence of
oxygen
 C6H12O6 + 6O2 = 6CO2 + 6 H2O + 36 ATP
 Anaerobic pathway (anaerobic respiration and fermentation) – this
can take place in the absence of oxygen (Some bacteria & yeast)
 C6H12O6 = 2 CO2 + 2 Ethanol + 2 ATP = alcoholic fermentation
 C6H12O6 = 2 Lactic Acid + 2 ATP = lactic acid fermentation

24. Cellular respiration
A. Aerobic pathway (aerobic respiration)
 it is a multi-step process
 There are four stages in the aerobic respiration of glucose. These are:
 Glycolysis
 the link reaction-pyruvate oxidation
 Krebs cycle
 electron transport Chain and chemiosmosis
1. Glycolysis/Glucose splitting /“breaking glucose”
 Glycolysis comes from two Greek words:
 Glykys = sweet
 Lysis = breakdown/ splitting
 process in which glucose molecule is broken down into two molecules of
pyruvic acid (a smaller molecule containing only three carbon atoms)
 it is takes place in the cytoplasm
 This unique pathway occurs aerobically as well as anaerobically &
doesn’t involve molecular oxygen
24

25. Glycolysis
 The entire glycolysis
pathway can be separated
into two phases:
 The Preparatory Phase – in
which ATP is consumed
and is hence also known
as the investment phase
 The Pay Off Phase – in
which ATP is produced.
 Characterized by a net gain
of the energy-rich
molecules ATP and
NADH.
25

26. Aerobic pathway - Glycolysis
 overall balance sheet of glycolysis
 Each molecule of glucose gives 2
molecules of Glyceraldehyde-3-
phosphate and which converted into 2
molecules of pyruvate
 The total molecules that are consumed
and produced in all reactions steps can
be summarized as:
 Starting material=1glucose molecule
 2 ATP molecules are utilized
 4 ATP molecules are released
 2 NADH molecules are released
 2H2O molecules released
 2 pyruvate molecules are produced
26
 Therefore , the total input of all the reactions can be summarized as:
 Glucose + 2ATP+ 2Pi+ 2NAD⁺+ 2H⁺+ 4ADP 2Pyruvate+ 2H⁺+ 4ATP+ 2H₂O+ 2NADH+ 2ADP
 On cancelling the common terms from the above equation, we get the net equation
for Glycolysis:
 Glucose + 2Pi+ 2ADP+ 2NAD⁺ 2Pyruvate+ 2H⁺+ 2ATP+ 2H₂O+ 2NADH+ 2ADP
 thus the simultaneous reactions involved glycolysis are:
 Glucose is oxidized to Pyruvate
 NAD⁺ is reduced to NADH
 ADP is phosphorylated to ATP

27. Aerobic pathway/ link reaction/pyruvate oxidation
 occurs in matrix of mitochondria
 oxidative decarboxylation occurs
 products:
 Acetyl CoA-goes to the Krebs cycle
 CO2-Exhale
 NADH-goes to ATP synthesis
 Pyruvic acid (3C) + CoA + NAD+
AcetylCoA +CO2 + NADH + H+
27
Pyruvate dehydrogenase

28. Aerobic pathway/ Citric Acid Cycle (Kreb’s Cycle)
 Termed as Citric Acid
Cycle/Tricarboxylic acid (TCA) cycle
 Also called Krebs cycle
 Discovered by Hans Krebs in 1937
 Occurs in matrix of mitochondria
 critic acid is the first product as well
as final reactant
 Begins by the addition of a two-carbon
acetyl group to a four-carbon molecule
(oxaloacetate), forming a six-carbon
molecule (citric acid)
 NADH, FADH2 capture energy rich
electrons
 ATP formed by substrate-level
phosphorylation
 Turns twice for one glucose molecule.
28
Out puts:
 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: 6 NADH, 2 FADH2, 2 ATP and 6
CO2

29. Aerobic pathway/ electron transport chain
 Occurs in inner membrane
 Main process of ATP synthesis, ~ 32
ATP
 High-energy electrons from NADH and
FADH2 are passed along the electron
transport chain from one carrier protein
to the next and release energy
 Requires oxygen, the final electron acceptor.
 e-, H+ and O2 combine to make H2O
 NADH + FADH2 + O2  ATP + H2O
 For every FADH2 molecule – 2 ATP’s are
produced.
 For every NADH molecule – 3 ATP’s are
produced.
 Chemiosmosis – the production of ATP
using the energy of H+ gradients across
membranes to phosphorylate ADP.
29

30. aerobic respiration
Net result of aerobic respiration
 Glycolysis –
 2 ATP
 2NADH= 4/6 ATP
 Pyruvate oxidation
 2NADH= 6ATP
 From citric acid cycle –
 2 ATP
 6NADH= 18 ATP
 2FDH2= 4ATP
 In electron transport chain:
 1 NADH produces 3 ATP
 1FDH2 produces 2 ATP
 Hence, at the end of aerobic respiration a total of 36/38
ATP molecules are produced/released.
30

31. Anaerobic pathways
31

32. Anaerobic pathways
32

33. Anaerobic pathways
33

34. 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.
34

35. Cont’d…
 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.
35

36. Photosynthesis
 Is the process by which autotrophic organisms use light energy to
make sugar and oxygen gas from carbon dioxide and water.

37.  It begins all food chains/webs. Thus all life is supported by this process.
 The processes of all organisms, from bacteria to humans require energy and to get this
energy, many organisms access stored energy by eating food.
Makes organic molecules (glucose) out of inorganic materials (carbondioxide and water). It also
makes oxygen gas..
 ORGANIC FOOD- Photosynthesis is the only process which produces organic food from in organic
raw materials. All organisms of the world are dependent on this organic food. Plants, which
manufacture food, are called producers. Others, which are directly or indirectly dependent upon
plants for food, are known as consumers.
 It is the only biological process that captures energy from outer space (sunlight) and
converts it into chemical energy in the form of Glyceraldehyde3-phosphate (G3P), which in
turn can be made into sugars and other organic compounds such as proteins, lipids, and
nucleic acids.
 Plants use these compounds in all of their metabolic processes.
Unlike plants, animals need to consume other organisms to consume the molecules they
need for their metabolic processes.
Importance of Photosynthesis

38. The process of photosynthesis
Where does photosynthesis takes
place ?

39. Where does pho/sis takes place

40. • 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
Chloroplast

41. Parts of chloroplast
 Thylakoids:
 flattened sacs like structure
contain pigment chlorophyll
 Individual discs are called thylakoids
 Grana (sing. granum):
 layered thylakoids (like pancakes)
 Stack /pile of thylakoids
 Stroma lamellae:
 flat tubules
 connect granal thylakoids
 Stroma:
 solution around thylakoids/Matrix
 contain DNA, Ribosome and proteins
 = Cytosol of the chloroplast
Granum
Thylakoid Space/lumen
Thylakoid

42. The process of photosynthesis
 Based on photosynthetic nature organisms
classified in to:
 Photoautotrophs
 Are organisms(plants, algae, and some bacteria)
which have a capability of performing photosynthesis
and they use light to manufacture their own food.
 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.
42

43. Cont’d…
Other variant of photosynthesis
 The process of photosynthesis might be oxygenic/
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 water (H2O) to carbon dioxide
(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.
43

44. 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.
44

45. Cont’d…
The photosynthetic apparatus
 Plastids
 Photosynthetic eukaryotic organisms contain
organelles called plastids in their cytoplasm.
 Plastids generally contain pigments or can store
nutrients.
 Colorless and nonpigmented leucoplasts store fats
and starch, while chromoplasts contain carotenoids
and chloroplasts contain chlorophyll.
Pigments
 Pigments are molecules that bestow color on plants,
algae and bacteria, but they are also responsible for
effectively trapping sunlight.
 Pigments of different colors absorb different
wavelengths of light. There are 3 main group of
45

46. Cont’d…
1. Chlorophylls
 These green-colored pigments are capable of trapping
blue and red light.
 Chlorophylls have three subtypes, dubbed chlorophyll
a, chlorophyll b and chlorophyll c.
 There is also a bacterial variant aptly named
bacteriochlorophyll, which absorbs infrared light.
 This pigment is mainly seen in purple and 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. 46

47. Photosynthetic pigment
• Chlorophyll a –
– blue green pigment
– primary pigment in plants
– necessary pigment
• Other pigments- accessory pigments
– secondary pigments absorbing light
wavelengths other than those absorbed by
chlorophyll a
– increase the range of light wavelengths
that can be used in photosynthesis. These
includes:
– chlorophyll b – yellow green in
color
– Xanthophylls- yellow
– Carotene- yellow-orange

48. Phases of Photosynthesis reaction
• Two main parts (reactions).
1. Light Reaction or Light
Dependent Reaction
 Produces energy from solar power
(photons) in the form of ATP and
NADPH
 directly light driven
 occur in thylakoid
2. Dark reaction/light independent
reaction
 Synthesis of sugar
 Occur in Stroma
 Uses energy (ATP and NADPH)

49. 1. Light Reaction (Electron Flow)
 ATP synthesis
 NADPH synthesis
 directly light driven
 occur in thylakoid
ADENOSINE TRIPHOSPHATE
ADENOSINE DIPHOSPHATE
ENERGY
RELEASED
Partially
charged
battery
Fully
charged
battery
Adenosine diphosphate (ADP) + Phosphate Adenosine triphosphate (ATP)
Energy
Energy
Solar energy Chemical energy / ATP/ NADPH

50. Light Reaction
• Photosystems:
• Clusters of chlorophyll and other pigments in the
thylakoid membrane (organized by a set of
proteins in the plant cell)
• Also called Light harvesting unit- Light-collecting
unit of the cell
• Also termed as Antennae
• 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.
• Each Photosystem is made up of:
– Reaction center – special pigment best at absorbing light
of specific wave length
– the pigments and proteins, which convert light energy to
chemical energy and begin the process of electron transfer,

51. Products of Light Reaction
ATP
NADPH
O2
Diffuse out of the chloroplast as by
product of Photosynthesis
Energy rich molecules – stroma-
used for sugar
synthesis

52. Calvin Cycle
• So what do we have from pour light-dependent rxns?
– High-E electrons stored in ATP and NADPH
– “chemical energy”
– But plants cannot store this chemical energy for more than a
few minutes…must change this chemical energy into something
that can be stored for long periods of time
• Calvin cycle:
– Uses ATP and NADPH from light-dependent rxn to produce high-E
sugars

53. Calvin Cycle
• Carbon Fixation (light
independent rxn).
• C3 plants (80% of plants on earth).
• Occurs in the stroma.
• Uses ATP and NADPH from light
rxn.
• Uses CO2.
• To produce glucose: it takes 6
turns and uses 18 ATP and 12
NADPH.

54. Calvin Cycle (C3 fixation)
Phase 1: Carbon Fixation
Phase 2. Reduction phase
Phase 3: Regeneration of
Starting Material (RuBP)

55. Ribulose-1,5-bisphosphate
(RuBP)
OH
H2C
C
H
C
C
OH
H
H2C OPO3
2-
OPO3
2-
O
3-Phosphoglycerate
(3PG)
OH
H2C
C
H
C
O
O
OPO3
2-
-
Ribulose-1,5-bisphosphate + CO2  2 (3-phosphoglycerate)
CO2
2
Ribulose Bisphosphate
Carboxylase (RuBP
Carboxylase
Phase 1: Carbon Fixation
the most abundant
protein on Earth!

56. Calvin Cycle (C3 fixation)
2. Reduction phase
 series of reduction of 3-PGA to form glucose
 ATP & NADPH produced during light reaction are used in this step
 each 3-PGA need 1ATP and 1NADPH
 6CO2 fixed to produce one molecule of glucose
OH
H2C
C
H
C
O
O
OPO3
2

OH
H2C
C
H
C
OPO3
2
O
OPO3
2
OH
H2C
C
H
CHO
OPO3
2
ATP ADP NADPH NADP+
Pi
1,3-bisphospho-
glycerate
3-phospho-
glycerate
glyceraldehyde-
3-phosphate
Phosphoglycerate
Kinase
Glyceraldehyde-3-phosphate
Dehydrogenase

57. Phase 3: Regeneration of Starting Material
(RuBP).
• A complex series of reactions rearranges the carbon
skeletons of five G3P molecules into three RuBP
molecules.
• These reactions require three ATP molecules.
• RuBP is thus regenerated to begin the cycle again.
• Triose Phosphate Isomerase, Aldolase, Fructose Bisphosphatase,
Sedoheptulose Bisphosphatase, Transketolase, Epimerase, Ribose
Phosphate Isomerase, & Phosphoribulokinase.

58. The Calvin cycle produces G3P

60. Cont’d…
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.
60

61. Adaptations to Limitations
• Photorespiration limitations:
– C3 plant
• Adaptations to hot, arid conditions:
– C4 plants
– CAM plants

62. Leaf Anatomy
• Plants whose first organic product of carbon fixation is a 3-carbon
compound
• In C3 plants (those that do C3 photosynthesis), all processes occur
in the mesophyll cells
• The bundle sheath cells of C3 plants do not contain
chloroplasts
Mesophyll cells
Bundle
sheath
cells

63. C3 Plant Limitations
• In hot, arid conditions, plants close
the stomata to prevent water loss
• What affect does that have on
CO2 and O2 concentration?
• Closed stomata O2 increases:
– rubisco binds to O2 rather than
CO2
– It is known as photorespiration
– skip the Calvin cycle
– glucose is not produced
http://evolution.berkeley.edu/evolibrary/images/interviews/stoma_diagram.gif

64. Rubisco activity and CO2 concentration
OH
H2C
C
H
C
O
O
OPO 3
2

H2C
C
OPO 3
2
O
O
3-phospho- phosphoglycolate
glycerate
yields
2x PGA
yields
1x PGA
& PG
PG/2c
• cannot be converted
directly into sugars
• is a wasteful loss of
carbon
• to retrieve the carbon
from it, plants must
use an energy-
expensive process
called photorespiration

65. C4/CAM Photosynthesis
• Certain plants have developed ways to limit the
amount of photorespiration
– C4 Pathway*
– CAM Pathway*
• Both convert CO2 into a 4 carbon intermediate
using PEP Carboxylase

66. • Preface the Calvin cycle with an alternate mode of carbon
fixation that produces a 4-carbon compound as their first
organic product
• Hot, moist environments.
• 15% of plants (grasses, corn, sugarcane).
• Divides photosynthesis spatially.
• incorporating CO2 into organic compounds in the mesophyll
• Calvin cycle - bundle sheath cells.
C4 Plants

67. C4 Pathway
• In C4 plants photosynthesis
occurs in both the mesophyll and
the bundle sheath cells.
• CO2 is fixed into a 4-carbon
intermediate
• Has an extra enzyme– PEP
Carboxylase that initially traps
CO2 instead of Rubisco– makes a
4 carbon intermediate

68. C4 Pathway
• PEP Carboxylase:
• Very high affinity for CO2
• Can fix carbon even when CO2 levels
decrease and O2 levels rise
• PEP (3C) + CO2  OAA (4C)
• OAA  Malate
• Malate  pyruvate (3C) + CO2
• Pyruvate  PEP
• The 4 carbon intermediate is
“smuggled” into the bundle sheath cell
• The bundle sheath cell is not very
permeable to CO2
• CO2 is released from the 4C malate 
goes through the Calvin Cycle
C3 Pathway

69. How does the C4 Pathway limit photorespiration?
• Bundle sheath cells are far
from the surface– less O2
access
• PEP Carboxylase doesn’t
have an affinity for O2
•  allows plant to collect a
lot of CO2 and concentrate
it in the bundle sheath cells
(where Rubisco is there)

70. CAM Plants
• CAM: Crassulacean acid
metabolism
• Succulent (water-storing) plants
• Hot, dry environments.
• 5% of plants
• Example: cacti, pineapples
• Stomata closed during day.
• Stomata open during the night.
• incorporating CO2 into organic
compounds at night time
• Calvin Cycle –day- occurs when
CO2 is present.

71. How does the CAM Pathway limit
photorespiration?
• Collects CO2 at night so that it can be
more concentrated during the day
• Plant can still do the Calvin cycle during
the day without losing water

73. Metabolic disorders, diagnosis and
treatments
 Metabolism is the breaking down of food to its simpler
components: proteins, carbohydrates (or 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.
 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. 73

74. Cont’d…
 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.
 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
74

75. Cont’d…
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) . 75

76. Carbohydrate
disorders
76
 Deficiency of antidiuretic hormone,
 resulting in an inability to conserve water
 Leading to polyuria
 Treatment: a low-salt diet and drinking
more water and reduce urination
 The lack of this enzyme results in an accumulation of
fructose-1-phosphate in the liver, kidney, and small
intestine.
 This accumulation, inhibits glycogen breakdown and
glucose synthesis, thereby causing severe
hypoglycaemia following ingestion of fructose & kidney
damage.
 The diagnosis is made by analysing a sample of liver
tissue.
 Treatment includes avoiding fructose in the diet and,
when needed, taking glucose tablets.
The ALDOB gene provides
instructions for making the
aldolase B enzyme
 Von Gierke disease is also called Type I glycogen
storage disease (GSD I)
 due to deficiency of G6P in the liver & kidney
 Resulting accumulation of glycogen in liver & disturb the
normal function of it
 Leading to enlargement of liver and kidney
 Fasting hypoglycaemia
 If both parents carry a nonworking copy of the gene
related to this condition, each of their children has a 25%
phosphoglucomutase
hereditary fructose intolerance

77. Fatty acid oxidation defects
77
Gaucher disease is a rare, inherited metabolic
disorder in which deficiency of the enzyme
glucocerebrosidase results in the accumulation of
harmful quantities of certain fats (lipids), specifically
the glycolipid glucocerebroside, throughout the body
especially within the bone marrow, spleen and liver
Niemann-Pick disease type C (NPC) is a
rare progressive genetic disorder
characterized by an inability of the body to
transport cholesterol and other fatty
substances (lipids) inside of cells. This leads
to the abnormal accumulation of these
substances within various tissues of the body,
including brain tissue.

78. Cont’d…
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
78

79. Cont’d…
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 less for men; 35
inches or less for women
 Elevated triglycerides: 150 mg/dL or higher
 Reduced high-density lipoprotein (HDL) levels (also known
as ''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 .
79

80. Cont’d…
 The treatment approach for metabolic disorders
depends on the specific disorder.
 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.
80

81. Diagnosis of metabolic disorders
81
Elevated triglycerides may
contribute to pancreatitis or
hardening of the arteries. This
increases the risk of stroke, heart
attack and heart disease.
 Triglycerides level:
 normal: less than 150mg/dL
 Elevated triglycerides: 150 mg/dL
or higher
Normal blood pressure is between 120/80 mm Hg and 129/84 mm Hg. If
your blood pressure is between 130/85 mm Hg and 139/89 mm Hg, you
have "high-normal" blood pressure, which is more likely to develop into
high blood pressure.
A fasting blood sugar level less than 100 mg/dL (5.6 mmol/L) is normal. A
fasting blood sugar level from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) is
considered prediabetes. If it's 126 mg/dL (7 mmol/L) or higher on two
separate tests, you have diabetes

82. 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.
82

83. 83