Chapter Four

Cellular Metabolism and

Metabolic Disorders
4.1. Cellular metabolism

• Living cells are in a constant activity. Macromolecules

are assembled and broken down, substances are
transported across cell membranes, and genetic
instructions are transmitted. All of these cellular activities
require energy.
• Metabolism is thus the sum of chemical reactions that
takes place within each cell of a living organism and that
provides energy for vital processes and synthesizing of
new organic materials.
• Broadly, these reactions can be divided into catabolic
reactions that convert nutrients to energy and anabolic
reactions that lead to the synthesis of larger
biomolecules.
• In metabolism, a series of chemical reactions in which
the product of one reaction is the substrate for the next
reaction is called a metabolic pathway.
• Catabolic pathways release energy by breaking down
larger molecules into smaller molecules. Anabolic
pathways use the energy released by catabolic
pathways to build larger molecules from smaller
molecules, insuring the continual flow of energy within an
organism.
• The reactants and products of these chemical reactions
are metabolites.
• The major classes of metabolites include proteins,
carbohydrates, nucleotides, lipids, coenzymes, and cofactors.
These classes of compounds encompass an enormous diversity
of molecular structures, physicochemical properties, functions,
and abundances.
• The most common criteria for this distinction rely on the
hydrophilic (polar) and hydrophobic (nonpolar) nature of
metabolites.
• Polar metabolites are soluble in aqueous solutions and
include most sugars, purines and pyrimidines,
nucleotides and nucleosides, acyl carnitines, organic
acids, hydrophilic acids, amino acids, and
phosphorylated compounds.
• These metabolites include most of the reactants and
products involved in cellular respiration (e.g., glycolysis,
the(tricarboxylic acid)TCA cycle, or in other pathways)
and in the production of building blocks for synthesis of
large biopolymers such as DNA, RNA, proteins, and
oligosaccharides.
• The nonpolar or hydrophobic metabolites are commonly
lipids.
• These metabolites function in energy storage,
membrane structure, and signal transduction.
• At the cellular level of organization, the main chemical
processes of all living matter are similar, if not identical.
• This is true for animals, plants, fungi, or bacteria; where
variations occur (such as, the secretion of antibodies by
some molds), the variant processes are but variations on
common themes.
• Thus, all living matter is made up of large molecules
called proteins, which provide support and coordinated
movement, as well as storage and transport of small
molecules, and, as catalysts, enable chemical reactions
to take place rapidly and specifically under mild
temperature, relatively low concentration, and neutral
conditions (i.e., neither acidic nor basic).
• The chemical reactions that take place in living cells are
similar as well. Green plants use the energy of sunlight
to convert water (H2O) and carbon dioxide (CO2) to
carbohydrates (sugars and starches), other organic
(carbon-containing) compounds, and molecular oxygen
(O2).
• The process of photosynthesis requires energy, in the
form of sunlight, to split one water molecule into one-half
of an oxygen molecule (O2; the oxidizing agent) and two
hydrogen atoms (H; the reducing agent), each of which
dissociates to one hydrogen ion (H+) and one electron.
• Through a series of oxidation-reduction reactions,
electrons (denoted e−) are transferred from a donating
molecule (oxidation), in this case water, to an accepting
molecule (reduction) by a series of chemical reactions;
this “reducing power” may be coupled ultimately to the
reduction of carbon dioxide to the level of carbohydrate.
• In effect, carbon dioxide accepts and bonds with
hydrogen, forming carbohydrates (Cn[H2O]n). Living
organisms that require oxygen reverse this process: they
consume carbohydrates and other organic materials,
using oxygen synthesized by plants to form water,
carbon dioxide, and energy.
• The process that removes hydrogen atoms
(containing electrons) from the carbohydrates
and passes them to the oxygen is an energy-
yielding series of reactions.
4.2. Enzymes and their role in metabolism

• In many cases, heat may be a catalyst, but

this is inefficient because heat cannot be
applied to molecules in a controlled fashion.
– Thus, most chemical reactions require
biological catalyst called enzymes.
What are enzymes and why they are needed?

• Enzymes are protein catalysts that speed

biochemical reactions by facilitating the
molecular rearrangements that support cell
function.
• Enzymes speed up (catalyze) chemical reactions;
in some cases, enzymes can make a chemical
reaction millions of times faster than it would
have been without it.
• Almost all metabolic processes in the cell need
enzyme catalysis in order to occur at rates fast
enough to sustain life.
• Enzymes bind with particular reactants until
the chemical reaction occurs, then free
themselves.
• Thus, at any given time, the numerous
pathways involved in building up and breaking
down cellular components must be monitored
and balanced in a coordinated fashion.
• To achieve this goal, cells organize reactions
into various enzyme-powered pathways.
 How do enzymes speed up chemical
reactions?
• Enzymes speed up reactions by lowering
activation energy.
• Many enzymes change shape when substrates
bind.
• This is termed "induced fit", meaning that the
precise orientation of the enzyme required for
catalytic activity can be induced by the binding of
the substrate.
• What is activation energy?
 4.2.1 Chemical nature and classification of enzymes

• All known enzymes are proteins with the

exception of recently discovered RNA
enzymes.
• Some enzymes may additionally contain a
non-protein group.
• Enzymes are high molecular weight
compounds made up principally of chains of
amino acids linked together by peptide bonds.
• Many enzymes require the presence of other compounds
(cofactors) before their catalytic activity can be exerted.
– This entire active complex is referred to as the holoenzyme; i.e.,
apoenzyme (protein portion) plus the cofactor (coenzyme, prosthetic
group or metal-ion-activator).
• Thus, on the basis of differences in chemical nature, the enzymes may be described
as follows:

• Simple enzymes:
– Simple enzymes are made up of only protein (polypeptide).
– They contain no chemical groups other than amino acid residues.
– Digestive enzymes such as pepsin, and trypsin are of this nature.
Conjugate Enzymes:
• It is an enzyme which is formed of two parts –
a protein part called apoenzyme (e.g.,
flavoprotein) and a non-protein part named
cofactor.
– The complete conjugate enzyme, consisting of an
apoenzyme and a cofactor, is called holoenzyme.
• There can be an enzymatic activity only when
both components (apoenzyme and cofactor)
are present together.
• The cofactor is sometimes a simple divalent metallic ion (e.g.
Ca, Mg, Zn, Co, etc), and sometimes a nonprotein organic
compound.
• However, some enzymes require both kinds of cofactors.
• If the cofactor is firmly bound to the apoenzyme, it is called
prosthetic group.
– For example, cytochromes are the enzymes that possess porphyrins as
their prosthetic groups.
• If, instead of being more or less permanently bound to the
apoenzyme the cofactor attaches itself to the apoenzyme only
at the time of reaction, it is called a coenzyme.
• Metallo-enzymes: The metal cofactors involved in enzymic
reactions are monovalent (K+) and divalent cations (Mg++,
Mn++ and Cu++).
– These may be loosely held by the enzyme, or as in some cases, go into
the composition of the molecule itself.
– If the metal forms part of the molecule, as iron of haemoglobin or
cytochrome is, the enzymes are called metallo-enzymes.
• Isoenzymes (Isozymes): At one time it was believed that an
organism has only a single enzyme for a given step of a
metabolic reaction.
– It was later discovered that a substrate may be acted upon by a number
of variants of an enzyme producing the same product.
 Classes of enzymes based on the substrate they act
up on

• Enzymes can be classified based on different

criteria of which classification based on the
substrate they acted up on is the most common
(Table 4.1).
Table4.1. Major classes of Enzymes
 4.2.2 Mechanisms of enzyme action
• Mechanisms of enzyme catalysis vary, but are all
similar in principle to other types of chemical catalysis
in that the crucial factor is a reduction of energy
barrier(s) separating the reactants from the products.
• The reduction of activation energy increases the
fraction of reactant molecules that can overcome this
barrier and form the product.
• An important principle is that since they only reduce
energy barriers between products and reactants,
enzymes always catalyze reactions in both directions,
and cannot drive a reaction forward or affect the
equilibrium position.
• An enzyme attracts substrates to its active site, catalyzes the
chemical reaction by which products are formed, and then
allows the products to dissociate (separate from the enzyme
surface). The combination formed by an enzyme and its
substrates is called the enzyme–substrate complex. The
substrates are attracted to the active site by electrostatic and
hydrophobic forces, which are called noncovalent bonds
because they are physical attractions and not chemical bonds.
• Do you recall enzyme models? Discuss on it in detail.
enzyme model
 4.2.3 Factors affecting enzymatic activities

• The activity of an enzyme is affected by its environmental

conditions such as temperature and pH. Changing these alter
the rate of reaction caused by the enzyme.
• In nature, organisms adjust the conditions of their enzymes to
produce an optimum rate of reaction, where necessary, or they
may have enzymes which are adapted to function well in
extreme conditions where they live.
Temperature
• Increasing temperature increases the kinetic energy that
molecules possess. In a fluid, this means that there are more
random collisions between molecules per unit time. Since
enzymes catalyse reactions by randomly colliding with
substrate molecules, increasing temperature increases the rate
of reaction, forming more product.
• However, increasing temperature also increases the
vibrational energy that molecules have, specifically
(in this case enzyme molecules), which puts strain
(damage) on the bonds that hold them together.
• As temperature increases, more bonds, especially the weaker
hydrogen and ionic bonds, will break as a result of this strain.
breaking bonds within the enzyme will cause the active site to
change shape.
• This change in shape means that the Active Site is less
complementary to the shape of the Substrate, so that it is less
likely to catalyse the reaction.
• Eventually, the enzyme will become denatured and will no
longer function. The temperature at which the maximum rate
of reaction occurs is called the enzyme‟s Optimum
Temperature. This is different for different enzymes.
Activity
• 1. Graphically, show the relationship between
enzyme activity and temperature.
• 2. What is the optimum temperature for most
enzymes in the human body?
pH - Acidity and Basicity
• pH is a measure of the hydrogen ion (H+)
concentration, and therefore a good indicator of
the hydroxide ion (OH-) concentration. Lower pH
values mean higher H+ concentrations and lower
OH- concentrations. H+ and OH- ions are charged
and therefore interfere with hydrogen and ionic
bonds that hold together an enzyme, since they
will be attracted or repelled by the charges created
by the bonds. This interference causes a change in
shape of the enzyme, and importantly, its active
site.
• Different enzymes have different optimum pH
values. This is the pH value at which the bonds
within them are influenced by H+ and OH- ions in
such a way that the shape of their active site is the
most complementary to the shape of their
substrate. At the optimum pH, the rate of reaction
is at an optimum. Any change in pH above or
below the optimum will quickly cause a decrease
in the rate of reaction, since more of the enzyme
molecules will have active sites whose shapes are
not (or at least are less) complementary to the
shape of their substrate.
• Small changes in pH above or below the optimum do
not cause a permanent change to the enzyme, since the
bonds can be reformed. However, extreme changes in
pH can cause enzymes to denature and permanently
lose their function. Enzymes in different locations of
our body have different optimum pH values since their
environmental conditions may be different. For
example, the enzyme pepsin functions best at around
pH-2 and is found in the stomach, which contains
hydrochloric acid. Because enzymes are sensitive to
changes in acidity, most living systems are highly
buffered; i.e., they have mechanisms that enable them
to maintain a constant acidity.
Substrate and enzyme concentration
• Changing the enzyme and substrate concentrations affect the
rate of reaction of an enzyme-catalysed reaction. Controlling
these factors in a cell is one way that an organism regulates its
enzyme activity and so its metabolism.
• Changing the concentration of a substance only affects the rate
of reaction if it is the limiting factor. If it is the limiting factor,
increasing concentration will increase the rate of reaction up to
a point, after which any increase will not affect the rate of
reaction.
• This is because it will no longer be the limiting factor and
another factor will be limiting the maximum rate of reaction.
As a reaction proceeds, the rate of reaction will decrease, since
the substrate will get used up.
Substrate concentration

• Increasing substrate concentration increases the

rate of reaction. This is because more substrate
molecules will be colliding with enzyme
molecules, so more product will be formed.
However, after a certain concentration, any
increase will have no effect on the rate of
reaction, since substrate concentration will no
longer be the limiting factor. The enzymes will
effectively become saturated, and will be working
at their maximum possible rate.
Enzyme concentration

• Increasing enzyme concentration will increase the

rate of reaction, as more enzymes will be
colliding with substrate molecules. However, this
too will only have an effect up to a certain
concentration, where the enzyme concentration is
no longer the limiting factor.
Activity
• Show graphically the relationships between
enzyme activity and substrate concentration as
well as enzyme concentration
Enzyme inhibitors

• Enzyme activity can be inhibited in various

ways. Inhibition could be reversible or
irreversible.
Reversible inhibition
• Competitive inhibition: occurs when
molecules very similar to the substrate
molecules bind to the active site and prevent
binding of the actual substrate. Penicillin, for
example, is a competitive inhibitor that blocks
the active site of an enzyme that many bacteria
use to construct their cell walls.
• Noncompetitive inhibition: occurs when an inhibitor
binds to the enzyme at a location other than the active
site. In some cases of noncompetitive inhibition, the
inhibitor is thought to bind to the enzyme in such a way
as to physically block the normal active site. In other
instances, the binding of the inhibitor is believed to
change the shape of the enzyme molecule, thereby
deforming its active site and preventing it from reacting
with its substrate. This latter type of noncompetitive
inhibition is called allosteric inhibition; the place
where the inhibitor binds to the enzyme is called the
allosteric site. Frequently, an end-product of a
metabolic pathway serves as an allosteric inhibitor on
an earlier enzyme of the pathway. This inhibition of an
enzyme by a product of its pathway is a form of
negative feedback.
• Activators: Allosteric control can involve
stimulation of enzyme action as well as
inhibition. An activator molecule can be bound
to an allosteric site and induce a reaction at the
active site by changing its shape to fit a
substrate that could not induce the change by
itself. Common activators include hormones
and the products of earlier enzymatic
reactions. Allosteric stimulation and inhibition
allow production of energy and materials by
the cell when they are needed and inhibit
production when the supply is adequate.
Irreversible inhibition
• Irreversible inhibitors usually covalently
modify an enzyme, and inhibition can
therefore not be reversed. Irreversible
inhibitors often contain reactive functional
groups. Irreversible inhibition is different from
reversible enzyme inactivation. Irreversible
inhibitors are generally specific for one class
of enzyme and do not inactivate all proteins;
they do not function by destroying protein
structure but by specifically altering the active
site of their target
Activity
[Link] other types of inhibition.
[Link] the concept of irreversible enzyme inhibition to drug
discovery and food poisoning.
[Link] how painkillers like ibuprofen relieved you from
pain.
[Link] is the difference between endothermic and exothermic
reaction?
[Link] is meant by a catalyst?
6. Why are several enzymes needed in a typical metabolic path
ways?
7. Which of the three ( coenzyme, cofactor, apoenzyme) is a
protein?
[Link] three factors that that influence enzymatic activity.
4.3 Bioenergetics and biosyntheses

4.3.1. Cellular respiration

• Most living organisms obtain energy by breaking
down organic molecules (catabolism) during cellular
respiration. The function of cellular respiration is to
harvest electrons from carbon compounds, such as
glucose, and use that energy to make Adenosine Tri
Phosphate (ATP). ATP is used to provide immediate
energy for cells to do work. 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 (Glycolysis). The chemical
reactions occurring during this stage do not release
much energy.
• Phase II - These building blocks are usually oxidized
to a common intermediate, acetyl - CoA.
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) followed by 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).
• tricarboxylic acid (TCA)
• Cellular respiration occurs in two main parts: glycolysis and
aerobic respiration. The first stage, glycolysis, is an anaerobic
process. Anaerobic metabolic processes do not require oxygen.
Aerobic respiration includes the Krebs cycle and electron
transport chain and is an aerobic process. Aerobic metabolic
processes require oxygen.
[Link]. Glycolysis: anaerobic respiration
• Glucose is a key metabolite in metabolism. Various
pathways that are concerned with the utilization, storage,
and regeneration of glucose exist. Glycogen is a polymeric
storage form of glucose in human and it is most abundant in
the liver and in striated muscle, although some is found in
other tissues also. Glycogen is synthesized when glucose
supply is high, and its degradation helps to maintain the
blood glucose level when we are fasting. When glycogen is
depleted, more glucose is synthesized from scratch in
gluconeogenesis. This pathway‟s most important substrates
are amino acids, which are obtained either from a protein-
rich diet-for example, during fasting on meat exclusively-or,
during starvation, from breakdown of cellular protein,
mainly in skeletal muscle. Gluconeogenesis occurs in the
liver and in the kidneys.
Self test
1. Define terms (glycolysis and gluconeogenesis)
2. Why glucose is more preferred by cells for respiration than
other carbohydrates/lipids?
3. How is anaerobic respiration differ from aerobic respiration?
[Link] are the three basic metabolic stages in respiration?
• The first step in the degradation of glucose is
glycolysis, which breaks down glucose to
pyruvate. The main purpose of glycolysis is
the generation of energy (ATP). A modest
amount of ATP is produced in glycolysis
directly, but much more ATP is formed
downstream of glycolysis through the
complete oxidation of pyruvate.
• Glycolysis is the most common pathway for glucose
degradation to pyruvate and is found in animals,
plants and microorganism. This pathway is used by
anaerobic as well as aerobic organisms. The process
takes place in the cytoplasm of prokaryotes and
eukaryotes and does not require oxygen. Under
aerobic conditions, most of the pyruvate formed in
glycolysis undergoes complete oxidative degradation
to CO2 and H2O.
• Pyruvate intended for complete degradation is
transported to the mitochondria, where it is
decarboxylated to acetyl-CoA by pyruvate
dehydrogenase. Acetyl-CoA is completely degraded
in the citric acid cycle (or tricarboxylic acid cycle;
TCA cycle for short). The “H2” that is produced here
is not gaseous but bound to co-substrates, as NADH
and FADH2, which is subsequently oxidized in the
respiratory chain.
• If glucose is available in excess of immediate needs
and glycogen is already stocked up to capacity, it will
still be broken down by glycolysis and pyruvate
dehydrogenase to acetyl-CoA. However, acetyl-CoA
will then not be oxidized, but it will instead be used
for fatty acid synthesis; the fatty acids are converted
to triacylglycerol. Fatty acid synthesis occurs in the
cytosol of cells in the liver and fat tissue .
• The first five are preparatory phases or
investment phase. Here, glucose is
phosphorylated, rearranged and
phosphorylated again, with the two phosphate
groups coming from ATP.
1. The phosphorylation of glucose at carbon-6 by
hexokinase forming glucose 6-phosphate (G6P).
 This reaction consumes ATP, but it acts to keep
the glucose concentration low, promoting continuous
transport of glucose into the cell through the plasma
membrane transporters.
• In addition, it blocks the glucose from leaking out – the cell
lacks transporters for G6P, and free diffusion out of the cell is
prevented due to the charged nature of G6P. Glucose may
alternatively be formed from the phosphorolysis or hydrolysis
of intracellular starch or glycogen.
• In animals, an isozyme of hexokinase called glucokinase is
also used in the liver, has a much lower affinity for glucose,
and differs in regulatory properties. The different substrate
affinity and alternate regulation of this enzyme are a reflection
of the role of the liver in maintaining blood sugar levels.
2. The conversion of glucose-6-phosphate(G6P) to fructose-6-
phosphate(F6P) by phosphohexose isomerase

•  The change in structure is an isomerization, in

which the G6P has been converted to F6P. This reaction
is freely reversible under normal cell conditions.
However, it is often driven forward because of a low
concentration of F6P, which is constantly consumed
during the next step of glycolysis. Under conditions of
high F6P concentration, this reaction readily runs in
reverse. This phenomenon can be explained through Le
Chatelier's Principle, ''Isomerization to a keto sugar is
necessary for carbanion(negative charge of carbon that
is stable) stabilization in the fourth reaction step
(below)''.
3. The phosphorylation of fructose-6-phosphate to the 1,6-
bisphosphate by phosphofructokinase

•  The energy expenditure of another ATP in

this step is justified in 2 ways: The glycolytic
process (up to this step) becomes irreversible, and
the energy supplied destabilizes the molecule.
Because the reaction catalyzed by
Phosphofructokinase 1 (PFK-1) is coupled to the
hydrolysis of ATP (an energetically favorable
step) it is, in essence, irreversible, and a different
pathway must be used to do the reverse
conversion during gluconeogenesis. This makes
the reaction a key regulatory point. This is also
the rate-limiting step.
• The second phosphorylation event is necessary
to allow the formation of two charged groups
(rather than only one) in the subsequent step of
glycolysis, ensuring the prevention of free
diffusion of substrates out of the cell.
• The same reaction can also be catalyzed by
pyrophosphate-dependent phosphofructokinase
(PFP or PPi-PFK), which is found in most
plants, some bacteria, archea, and protists, but
not in animals. This enzyme uses
pyrophosphate (PPi) as a phosphate donor
instead of ATP. It is a reversible reaction,
increasing the flexibility of glycolytic
metabolism.
• The cleavage of fructose-1,6-bisphosphate by
aldolase. This yields two different products,
dihydroxyacetone phosphate and glyceraldehyde-
3-phosphate,
Destabilizing the molecule in the previous
reaction allows the hexose ring to be split by
aldolase into two triose sugars: dihydroxyacetone
phosphate (a ketose), and glyceraldehyde 3-
phosphate (an aldose). There are two classes of
aldolases: class I aldolases, present in animals and
plants, and class II aldolases, present in fungi and
bacteria; the two classes use different mechanisms
in cleaving the ketose ring.
• Electrons delocalized in the carbon-carbon
bond cleavage associate with the alcohol
group. The resulting carbanion is stabilized by
the structure of the carbanion itself via
resonance charge distribution and by the
presence of a charged ion prosthetic group.
5. The isomerization of dihydroxyacetone
phosphate to a second molecule of
glyceraldehyde-3-phosphate by triose phosphate
isomerase,
Triosephosphate isomerase rapidly interconvert
dihydroxyacetone phosphate with glyceraldehyde 3-
phosphate (GADP) that proceeds further into glycolysis.
This is advantageous, as it directs dihydroxyacetone
phosphate down the same pathway as glyceraldehyde 3-
phosphate, simplifying regulation.
Remember!!
• The rest five are pay-off phases which are characterised by a
net gain of the energy-rich molecules ATP and NADH. Since
glucose leads to two triose sugars in the preparatory phase,
each reaction in the pay-off phase occurs twice per glucose
molecule. 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. Along
the way, the two molecules are rearranged into pyruvate.
6. The dehydrogenation and concomitant phosphorylation
of glyceraldehyde-3-phosphate to 1,3-bis-
phosphoglycerate by glyceraldehyde-3-phosphate
dehydrogenase,
The aldehyde groups of the triose sugars are oxidised, and
inorganic phosphate is added to them, forming 1,3-
bisphosphoglycerate.
The hydrogen is used to reduce two molecules of NADH, a
hydrogen carrier, to give NADH + H+ for each triose.
Hydrogen atom balance and charge balance are both
maintained because the phosphate (Pi) group actually exists in
the form of a hydrogen phosphate anion (HPO42-), which
dissociates to contribute the extra H ion and gives a net charge
of -3 on both sides.
• Note that: Arsenate (AsO43−), an anion similar to inorganic
phosphate may replace phosphate as a substrate to form 1-
arseno-3-phosphoglycerate. This, however, is unstable and
readily hydrolyzes to form 3-phosphoglycerate, the
intermediate in the next step of the pathway. As a consequence
of bypassing this step, the molecule of ATP generated from 1-3
bisphosphoglycerate in the next reaction will not be made,
even though the reaction proceeds. As a result, arsenate is an
uncoupler of glycolysis during Arsenic poisoning.
7. The transfer of the 1-phosphate group from 1,3-bis-
phosphoglycerate to ADP by phosphoglycerate kinase,
which yields ATP and 3-phosphoglycerate.
 At this step, glycolysis has reached the break-even
point: 2 molecules of ATP were consumed, and 2 new
molecules have now been synthesized. This step, one of
the two substrate-level phosphorylation steps, requires
ADP; thus, when the cell has plenty of ATP (and little
ADP), this reaction does not occur.
Because ATP decays relatively quickly when it is not
metabolized, this is an important regulatory point in the
glycolytic pathway.
 ADP actually exists as ADPMg−, and ATP as
ATPMg2−, balancing the charges at -5 both sides.
• 8. The isomerization of 3-phosphoglycerate to
2-phosphoglycerate by phosphoglycerate
mutase(PGAM),
• Note that: PGAM plays an important role in coordinating
glycolysis and anabolic activity to promote cancer cell
proliferation. It is suggested that even under aerobic
conditions cancer cells can show a high rate of glycolysis and
increased production of lactate, generating ATP faster than
normal cells. However, to obtain sufficient ATP and carbons to
generate biomass [nucleotides, amino acids, lipids and
nicotinamide adenine dinucleotide phosphate (NADPH)]
cancer cells must uptake more glucose than normal cells to
meet the metabolic requirements of rapid cell proliferation
owing to the low efficiency of glycolysis.
9. The dehydration of 2-phosphoglycerate to
phosphoenolpyruvate by enolase.
10. The transfer of the phosphate group from
phosphoenolpyruvate to ADP by pyruvate kinase, to
yield a second molecule of ATP.
A final substrate-level phosphorylation now forms
a molecule of pyruvate and a molecule of ATP by
means of the enzyme pyruvate kinase. This serves as
an additional regulatory step, similar to the
phosphoglycerate kinase step.
• Most, but not all reactions in glycolysis are reversible; this can
be indicated by different arrows (as indicated in Fig.).
Because it contains several irreversible reactions, the pathway
as a whole is also irreversible. However, alternate routes exist
that bypass the irreversible reactions and allow glucose to be
synthesized from pyruvate.
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. The reverse
reaction, breaking down, e.g., glycogen, produces
mainly glucose-6-phosphate; very little free glucose is
formed in the reaction. The glucose-6-phosphate so
produced can enter glycolysis after the first control
point.
• In the second regulated step (the third step of
glycolysis), phosphofructokinase converts
fructose-6-phosphate into fructose-1,6-
bisphosphate, which then is converted into
glyceraldehyde-3-phosphate and
dihydroxyacetone phosphate.
• The dihydroxyacetone phosphate can be removed
from glycolysis by conversion into glycerol-3-
phosphate, which can be used to form
triglycerides. Conversely, triglycerides can be
broken down into fatty acids and glycerol; the
latter, in turn, can be converted into
dihydroxyacetone phosphate, which can enter
glycolysis after the second control point.
Fig: 4.1. Glycolysis steps
[Link]. TCA cycle and ETC: Aerobic respiration
• One fate of pyruvate is that it enters to TCA cycle for
complete oxidation. But there are intermediate
processes that convert pyruvate to a acetyl coA. The
enzyme complex converts pyruvate into Acetyl-CoA
by the following chemical changes:
 Decarboxylation of pyruvate (loss of CO2)
 Formation of acetyl group
 Linkage of acetyl group to coenzyme A forming acetyl -
CoA.
The Tricarboxylic Acid (TCA) Cycle (Phase III)

• The TCA cycle also called Krebs or Citric acid cycle,

is considered as central pathway of aerobic
metabolism, as it serves two purposes-bioenergetics
and biosynthesis:
• 1. Bioenergetic - 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).
• TCA oxidizes two-carbon units, producing two
molecules of CO2, one molecule of GP, and high-
energy electrons in the form of NADH and FADH2.
Steps of the Krebs cycle

• Prior to the Krebs cycle, pyruvate first reacts with

coenzyme A (CoA) to form a 2-carbon intermediate
called acetyl CoA. At the same time, carbon dioxide
is released and NAD is converted to NADH.
• Acetyl CoA then moves to the mitochondrial matrix.
The reaction results in the production of two carbon
dioxide molecules and two NADH.
• The Krebs cycle begins with acetyl CoA combining
with a 4-carbon compound to form a 6-carbon
compound known as citric acid.
• Citric acid is then broken down in the next
series of steps, releasing two molecules of
carbon dioxide and generating one ATP, three
NADH, and one FADH . FAD is another
electron carrier similar to NADH and NADPH.
Finally, acetyl CoA and citric acid are
generated and the cycle continues.
Fig: 4.2. The TCA cycle
• Recall that two molecules of pyruvate are formed
during glycolysis, resulting in two “turns” of the
Krebs cycle for each glucose molecule. The net yield
from the Krebs cycle is six carbon dioxide molecules,
two ATP, eight NADH, and two FADH2 . NADH and
FADH2 move on to play a significant role in the next
stage of aerobic respiration.
2. Biosynthesis - It supplies precursors for several biosynthetic
pathways of amino acids, pyrimidines, purines etc.
 As already mentioned, the TCA cycle is also an important
source of biosynthetic precursors
 e.g. α-ketoglutarate and oxaloacetate are used for synthesis
of a number of amino acids like glutamic acid, asparatic
acid etc.
 Succinyl - CoA is used to form porphyrin ring of
cytochromes, chlorophyll etc.
 Oxaloacetate can also be converted to
phosphoenolpyruvate, which is a precursor of glucose.
 Acetyl - CoA is the starting material for fatty acid
biosynthesis.
[Link].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 and hydrogen
ions from NADH and FADH2 produced in the
Krebs cycle are used to convert ADP to ATP.
Fig:4.3. Electron Transport Chain
• As shown in Fig 4.3., electrons move along the
mitochondrial membrane from one protein to another.
As NADH and FADH2 electrons, the energy carriers are
converted to NADH release and FAD, and H ions are
released into the mitochondrial matrix. The H ions are
pumped into the mitochondrial matrix across the inner
mitochondrial membrane. H ions then diffuse down
their concentration gradient back across the membrane
and into the matrix through ATP synthase molecules in
chemiosmosis. Electron transport and chemiosmosis in
cellular respiration are similar to these processes in
photosynthesis. Oxygen is the final electron acceptor in
the electron transport system in cellular respiration.
Protons and electrons are transferred to oxygen to form
water.
• Activity
• [Link] is the overall chemical reaction of
aerobic reparation?
• 2. How many ATP molecules are collected
during electron transport chain and
chemiosmosis from a single glucose?
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 nucleotides. Biosynthesis is
usually synonymous with anabolism.
• The prerequisite elements for biosynthesis include: precursor
compounds, chemical energy (e.g. ATP), and catalytic
enzymes which may require coenzymes ([Link],
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.
Requirements of Biosynthesis
• Sometimes all that is required for biosynthesis
is for two substances to physically join
together to make a new physical substance,
which is called a macromolecule.
• A very simplified equation for biosynthesis of
one form of macromolecule: two substances
join together to form a new, more complex
substance.
i. Photosynthesis
• Energy is transformed all around us every day. Batteries
convert chemical energy into electric energy, and radios
convert electric energy into the energy carried by sound waves.
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. 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? All of this
energy can be traced back to the process of photosynthesis and light
energy from the sun. 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 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; plants do not need to consume other organisms for food
because they build all the molecules they need. Unlike plants,
animals need to consume other organisms to consume the molecules
they need for their metabolic processes.
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. How long lasting and
stable are those covalent bonds? The energy
extracted today by the burning of coal and
petroleum products represents sunlight energy
captured and stored by photosynthesis almost 200
million years ago.
• Plants, algae, and some bacteria such as
cyanobacteria are the only organisms capable of
performing photosynthesis. Because they use light
to manufacture their own food, they are called
photoautotrophs (“self-feeders using light”).
Other organisms, such as animals, fungi, and most
other bacteria, are termed heterotrophs (“other
feeders”) because they must rely on the sugars
produced by photosynthetic organisms for their
energy needs. A third very interesting group of
bacteria synthesize sugars, not by using sunlight‟s
energy, but by extracting energy from inorganic
chemical compounds; hence, they are referred to
as chemoautotrophs.
• The importance of photosynthesis is not just that it can
capture sunlight‟s energy. A lizard sunning itself on a
cold day can use the sun‟s energy to warm up.
Photosynthesis is vital because it evolved as a way to
store the energy in solar radiation (the''photo'' part) as
high-energy electrons in the carbon-carbon bonds of
carbohydrate molecules (the ''synthesis'' part). Those
carbohydrates are the energy source that heterotrophs
use to power the synthesis of ATP via respiration.
Therefore, photosynthesis powers 99 percent of Earth‟s
ecosystems. When a top predator, such as a wolf, preys
on a deer, the wolf is at the end of an energy path that
went from nuclear reactions on the surface of the sun,
to light, to photosynthesis, to vegetation, to deer, and
finally to wolf.
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 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.
• 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.
• Anoxygenic photosynthesis does not produce oxygen.
What is produced depends on the electron donor. For
example, many bacteria use the bad-eggs-smelling
gas hydrogen sulfide, producing solid sulfur as a
byproduct.
• Though both types of photosynthesis are complex, multistep
affairs, the overall process can be neatly summarized as a
chemical equation.
• Oxygenic photosynthesis is written as follows:
6CO2 + 12H2O + Light Energy → C6H12O6 + 6O2 + 6H2O

Similarly, the various anoxygenic photosynthesis reactions can be

represented as a single generalized formula:
CO2 + 2H2A + Light Energy → [CH2O] + 2A + H2O
• The letter A in the equation is a variable and
H2A represents the potential electron donor.
For example, A may represent sulfur in the
electron donor hydrogen sulfide (H2S).
Self test
• 1. What cellular components are essential to
photosynthesis?
• 2. why plant leaves vary in color?
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.
• 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.
The empty spaces between columns of grana
constitute the stroma.
• 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. These genes encode
proteins essential to the organelle and to
photosynthesis. Like mitochondria,
chloroplasts are also thought to have originated
from primitive bacterial cells through the
process of endosymbiosis.
Fig: 4.4. structure of chloroplast
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. Below are the three main
groups.
• 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.
Fig: 4.5. basic structure of major photosynthetic pigments
• Carotenoids: These red, orange or yellow-colored pigments
absorb bluish-green light. Examples of carotenoids are
xanthophyll (yellow) and carotene (orange) from which carrots
get their color.
• 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.
• Antennae
• 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.
• Ultimately, light energy must be transferred to a pigment-
protein complex that can convert it to chemical energy, in the
form of electrons. In plants, for example, light energy is
transferred to chlorophyll pigments. The conversion to
chemical energy is accomplished when a chlorophyll pigment
expels an electron, which can then move on to an appropriate
recipient.
Reaction centers
• The pigments and proteins, which convert light energy to
chemical energy and begin the process of electron transfer, are
known as reaction centers.
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 reactions (also called light reactions): 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 (adenosine triphosphate, a source of chemical
energy for cells) and NADPH. 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. 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.
• In the first step of the Calvin cycle called carbon
fixation, six carbon dioxide (CO) molecules combine
with six 5-carbon compounds to form twelve 3-carbon
molecules called 3-phosphoglycerat (3-PGA). The
joining of carbon dioxide with other organic molecules
is called carbon fixation.
•  In the second step, the chemical energy stored in
ATP and NADPH is transferred to the 3-PGA
molecules to form high-energy molecules called
glyceraldehyde 3-phosphates (G3P). ATP supplies the
phosphate groups for forming G3P molecules, while
NADPH supplies hydrogen ions and electrons.
• In the third step, two G3P molecules leave the cycle to be used
for the production of glucose and other organic compounds. In
the final step of the Calvin cycle, an enzyme called rubisco
converts the remaining ten G3P molecules into 5-carbon
molecules called ribulose 1,5-bisphosphates (RuBP). These
molecules combine with new carbon dioxide molecules to
continue the cycle.
Fig:4.6. Calvin cycle
• Because rubisco converts inorganic carbon dioxide molecules
into organic molecules that can be used by the cell, it is
considered one of the most important biological enzymes.
Plants use the sugars formed during the Calvin cycle both as a
source of energy and as building blocks for complex
carbohydrates, including cellulose, which provides structural
support for the plant.
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.
• C4 plants one adaptive pathway that helps plants
maintain photosynthesis While minimizing water loss is
called the C4 pathway. The C4 pathway occurs in
plants such as sugar cane and corn. These plants are
called C4 plants because they fix carbon dioxide into
four-carbon compounds instead of three-carbon
molecules during the Calvincycle. C4 plants also have
significant structural modifications in the arrangement
of cells in the leaves. In general, C4 plants keep their
stomata (plant cell pores) closed during hot days, while
the four carbon compounds are transferred to special
cells where CO2 enters the Calvin cycle. This allows for
sufficient carbon dioxide uptake, while simultaneously
minimizing water loss.
• CAM plants Another adaptive pathway used by some
plants to maximize photosynthetic activity is called
crassulacean acid metabolism (CAM photosynthesis).
The CAM pathway occurs in water conserving plants
that live in deserts, salt marshes, and other
environments where access to water is limited. CAM
plants, such as cacti, orchids, and the pineapple allow
carbon dioxide to enter The leaves only at night, when
the atmosphere is cooler and more humid. At night,
these plants fix carbon dioxide into organic compounds.
During the day, carbon dioxide is released from these
compounds and enters the Calvin cycle. This pathway
• Also allows for sufficient carbon dioxide uptake, while
minimizing water loss.
4.4. Metabolic disorders, diagnosis and treatments

Self test
1. What are the risk factors for metabolic disorders?
2. How are metabolic disorders treated?
• 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
• Inherited metabolic disorders 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.
• There are numerous examples of inherited metabolic disorders,
which can be classified based on the type of food-related
building block that they affect, including amino acids (the
building block for proteins), carbohydrates, and fatty acids (the
building block for fats). 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, Pompe‟s 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
• Acid-base imbalance, Disorders of calcium
metabolism, DNA repair-deficiency disorders,
Iron metabolism disorders, Mitochondrial
diseases, Phosphorus metabolism disorders,
Malabsorption syndromes, Water-electrolyte
imbalance are some of the disorders associated
with metabolism.
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)
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 (includes any type of kidney problem,
such as kidney stones, kidney failure and kidney
anomalies) and Diabetes (it is more likely to have
metabolic syndrome if a person had diabetes during
pregnancy (gestational diabetes) or if he/she have a
family history of type 2 diabetes.
• Family history of genetic metabolic disorder.
• Race and ethnicity: people with African, Hispanic, First
Nations, Asian, and Pacific Islander backgrounds are at
higher risk than whites for type 2 diabetes.
• HIV/AIDS and other diseases; the risk of metabolic
syndrome is higher if a person ever had nonalcoholic fatty
liver disease, polycystic ovary syndrome or sleep apnea
• Age- the risk of metabolic syndrome increases with age.
• Obesity and lack of exercise: carrying too much weight,
especially in your abdomen, increases your risk of
metabolic syndrome
• Hormone imbalance: a hormone disorder such
as polycystic ovary syndrome (PCOS), a
condition in which the female body produces
too much of certain hormones, is linked with
metabolic syndrome.
• Insulin resistance: a situation in which a body
cannot use insulin properly.
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
– 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
Treatments
• The treatment approach for metabolic disorders
depends on the specific disorder. Inborn errors of
metabolism (inherited metabolic disorders) are often
treated with nutritional counseling 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 counseling, surgery to
relieve pain or symptoms, vitamin supplementation and
etc.
• Acquired metabolic disorder treatment will include
normalizing the metabolic balance by both reversing the cause
and administering medications.
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.
Activity
1. What are the risk factors of metabolic disorders?
2. How are metabolic disorders treated?
3. Write down the common metabolic disorders and their
symptoms.
Summary
• Phenylketonuria is an example of an inherited metabolic
disorder characterized by an inability to break down one of the
building blocks of protein, the amino acid phenylalanine.
• Type I diabetes, a disease in which the pancreas does not
create enough insulin to maintain balanced blood sugar levels,
is a metabolic disorder of sugar metabolism.
• An example of a metabolic disorder affecting fat metabolism is
Gaucher’s disease, which is characterized by a lack of the of
the enzyme glucocerebrosidase.