MC1: BIOCHEMISTRY

UNIVERSITY OF THE CORDILLERAS

COLLEGE OF NURSING
INSTRUCTOR: MRS. BEVERLY B. SANTOS - BENTRES

Let Us Set Our Objectives!

At the end of the lesson, the students will be able to:

▪ Compare the different structural classifications of carbohydrates
▪ Explain the metabolism of carbohydrates in the body.
▪ Determine common sources of carbohydrates.
▪ Have an in -depth understanding of increase or decrease levels of
blood glucose in the body, and plan nursing interventions to such
situations.

CARBOHYDRATES
▪ Considered as the most abundant biomolecules on earth, and the
simplest among the four types of organic compounds.
▪ They are produced through photosynthesis, an endothermic reductive
condensation of carbon dioxide, needing light energy and the pigment,
chlorophyll.
▪ They are polyhydroxy aldehydes or ketones and substances that yield
such compounds on hydrolysis.
▪ Empirical Formula: (CH2O)n, in which the ratio of C:H:O is 1:2:1. This
formula explains the origin of the term carbohydrate – it is composed of
carbon (carbo) and water (hydrate).
▪ Apart from certain polysaccharides, carbohydrates are white solids, and
freely soluble in water.
▪ Carbohydrates with lower molecular weight have sweet taste (sugars).

BIOLOGICAL SIGNIFICANCE
1. Carbohydrates are the basic fuel molecules of the cell.
▪ When oxidized in the body, they liberate carbon dioxide (CO2), water,
and energy.
▪ Supply the major portion of energy required by living cells.
▪ Brain cells and red blood cells are most wholly dependent on
carbohydrates as a source of energy.

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2. Certain products of carbohydrate metabolism act as catalyst e.g.
Carbohydrate Active Enzyme (CAZy)
3. Certain carbohydrates are the starting materials for the biological
synthesis of fatty acids and amino acids.
4. Carbohydrates save proteins from being used for the production of
energy – protein-sparing function.

STRUCTURAL ISOMERS
▪ Same molecular formula (C6H12O6), but the arrangement of atoms differs
in their physical and chemical properties because the placement of their
chemical bonds – their atoms are bonded differently.

GLYCOSIDIC BOND
▪ A covalent bond that is formed between a carbohydrate molecule and
another molecule such as between two monosaccharides.

EPIMERS
▪ Two sugars that differ from one another only in the configuration around a
single carbon atom.

EPIMERIZATION
▪ Occurs in the tissues such as the conversion of galactose in the liver to
glucose. The conversion is catalyzed by an enzyme epimerase.

FUNCTIONAL GROUPS:
1. ALDOSE
▪ Sugars having an aldehyde function or an acetal equivalent
▪ The monosaccharide is an aldehyde if the carbonyl group is at the end
of the carbon chain. E.g. Glyceraldehyde

2. KETOSE
▪ Sugars having a ketone function or an acetal equivalent
▪ The monosaccharide is a ketone if the carbonyl group is at any other
position. E.g. dihydroxyacetone

Number of carbon atoms Monosaccharides

(backbones)
Four Tetrose/s
Five Pentose/s
Six Hexose/s
Seven Peptose/s

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THREE MAJOR CLASSES OF CARBOHYDRATES
▪ Saccharide comes from Greek word “sakkharon”, which means
“sugar”.

1. MONOSACCHARIDES (“mono”- “one”)

▪ “Simple sugars”, consisting of a single polyhydroxy aldehyde or ketone
unit.
▪ Smallest carbohydrates with three to seven carbon atoms (some
books: five to six).
▪ They are either aldehydes or ketones, having one or more hydroxyl
group. For instance, the fructose has five hydroxyl groups.
▪ The most common monosaccharide is glucose or the “blood sugar”
with a formula of C6H12O6.
▪ Some common monosaccharides also include galactose (part of
lactose) and fructose (found in sucrose, fruits).
▪ Stereoisomerism is common among monosaccharides and the carbon
atoms to which the hydroxyl groups are attached are often chiral
centres.

2. OLIGOSACCHARIDES
▪ These are composed of short chains of monosaccharide units that are
joined together by characteristic glycosidic linkages.
▪ Disaccharides (“di” – two) are most abundant with two
monosaccharide units that are joined together through dehydration
synthesis.
▪ For example, sucrose (table sugar) is formed when glucose bonds to
fructose. Lactose (milk sugar) is consisting of monomers of glucose and
galactose. Maltose (malt sugar) is formed from tow monomers of
glucose.
▪ Trisaccharides e.g. Raffinose

All common monosaccharides and disaccharides have names ending with the
suffix “-ose”.

3. POLYSACCHARIDES (“poly”- “many”)

▪ These are long chains of monosaccharide units linked by glycosidic
bonds, including cellulose that occur in linear chains and glycogen
with branch chains.
▪ The most abundant polysaccharide in nature, starch and cellulose are
consist of recuring units of D-glucose.

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REACTIVITY:
Reducing
▪ Sugars oxidized by Tollens’ or Benedict’s or Fehling’s reagents.
Non-reducing
▪ Sugars not oxidized by Tollens’ or other reagents.

METABOLISM
▪ The sum of all chemical reactions required for the nutritional and
functional activities of the cell.

FOUR SPECIFIC OBJECTIVES:

a. To extract chemical energy from the environment such as from organic
nutrients or from sunlight.
b. To convert exogenous nutrients to building blocks or precursors of
macromolecular components of the cell.
c. To assemble building blocks into CHO, CHON, LIPIDS, NUCLEIC ACIDS and
another characteristic cell compound.
d. To form (anabolism) and degrade (catabolism) these biomolecules
needed for the specialized functions of the cell.

ROUTES OF METABOLISM
a. Exogenous
▪ Food particles do not become part of our body tissues but are oxidized to
produce energy.
▪ Energy is released than absorb.

b. Endogenous
▪ Food particles became part of our body tissues.
▪ Energy is absorbed than it is released.

For example, exergonic reactions occur when food nutrients are broken down
and energy is released from these nutrients. Endergonic reactions occur when the
energy from these nutrients are used in building body structures such as muscles
and bones.

METABOLISM OF CARBOHYDRATES

1. It starts in the mouth, in which salivary amylase breaks down starches and
other polysaccharides, into constituent monosaccharides.
2. In the stomach, acid hydrolysis may occur sparingly while the action of
the enzymes of the saliva is arrested by the acid pH.
3. Pancreatic juice, containing carbohydrate-splitting enzymes is released in
the small intestine, in which they rapidly break down polysaccharides to
monosaccharides.

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4. Monosaccharides (predominantly glucose, fructose, and galactose) are
absorbed into the mucosa cells of the intestine through Na+ dependent-
active transport mechanism using a glucose co-transported, leaving the
cells into the portal circulation via facilitated diffusion in the presence of
glucose – transporters.
5. In the liver, two major mechanisms operate, glucose –
a. carbohydrate is either withdrawn from blood into the cells, to further
undergo breakdown for ultimate release of energy to power cellular
processes;
b. it is converted to storage forms to be drawn upon when the body later
needs energy (including conversion to fatty acids and stored as
triglycerides).

FATE OF GLUCOSE
▪ Uptake by different tissues through facilitated diffusion.
▪ Utilization by the tissues in the form of:

A. OXIDATION TO PRODUCE ENERGY

▪ Major pathways (glycolysis and Krebs’ cycle)
▪ Minor pathways (hexose monophosphate pathway and uronic acid
pathway)

For energy production, glucose is oxidized in a series of steps and pathways that
leads to its complete catabolism, producing Adenotriphosphate (ATPs), carbon
dioxide and water.

B. CONVERSION TO OTHER SUBSTANCES

▪ Carbohydrates: Ribose (RNA, DNA), galactose (in milk), fructose
(semen)
▪ Lipids: Glycerol-4 P for formation of triacylglycerides
▪ Proteins: Non-essential amino acids that enter in formation of proteins.

C. STORAGE OF EXCESS GLUCOSE

▪ As glycogen in liver and muscles, when these reserves are filled, it is
converted to TAGs (triacylglycerides) and deposited in adipose tissue.

D. EXCRETION IN URINE
▪ If blood glucose exceeds renal threshold (180mg/dL), it will be
excreted in urine.

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GLUCOSE “BLOOD SUGAR”
CONCENTRATION OF BLOOD SUGAR
▪ Fasting blood glucose (8-12 hours after the last meal) is 70-110 mg/dL
▪ It increases after meals but returns to fasting level within two hours.

SOURCES OF BLOOD GLUCOSE

▪ Dietary carbohydrates
▪ Glycogenolysis – during fasting for less than 18 hours.
▪ Gluconeogenesis – during fasting for more than 18 hours.

METABOLIC PATHWAYS
▪ A sequence of chemical reactions undergone by a compound or class of
compound in a living organism.

CELLULAR RESPIRATION
▪ A series of metabolic pathways that extracts the energy from the bonds of
glucose, converting it into a form (ATP) that can be used by living
organisms – both producers (plants) and consumers (animals).
o The energy released is trapped in the form of ATP for use by all the
energy-consuming activities of the cell
▪ The process of oxidizing food molecules, like glucose, to carbon dioxide
and water.

AEROBIC CELLULAR RESPIRATION

▪ The process by which a cell uses O2 to "burn" molecules and release
energy.
▪ The reaction: C6H12O6 + 6O2 ------------------→ 6CO2 + 6H2O
(Note: this reaction is the opposite of photosynthesis)

ANAEROBIC CELLULAR RESPIRATION

▪ This process allows organisms to convert energy for their use without the
presence of oxygen.

The cell controls its metabolism. It generates a number of intermediate

compounds used in the anabolism and catabolism of macromolecules. Cellular
respiration must be regulated to provide balanced amounts of energy in the form
of ATP. The process of cellular respiration is accomplished through the control of
specific enzymes in the pathways. (Rye, et.al, 2017)

REGULATORY MECHANISMS
▪ Cellular respiration is controlled by variety of mechanisms such as GLUT
(glucose transporter) proteins that controls the transport of glucose into
the cells of specific tissues.

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GLUT4 is a glucose transporter stored in vesicles. In the

presence of insulin, Glut4 fuses with the plasma
membrane to allow glucose into the cell.

CONTROL OF CATABOLIC PATHWAYS

▪ These includes enzymes, proteins, electron carriers,
and pumps that play roles in glycolysis, the citric acid cycle, and the electron
transport chain managing catalytic reactions.

I. GLYCOLYSIS
▪ From Greek word “glykys”, meaning “sweet” and “lysis” which means
“breaking”.
▪ Initially explained by Gustav Embden and Otto Meyerhof
▪ The process of converting glucose into energy. The body has two types of
reactions:
o Building of products such as muscle or glucose
o Breaking down of products.

▪ Energy is created when products are being broken down. Glycolysis is one
process that breaks down products, creating energy.

▪ Glucose is broken down to two molecules of 3-C compounds, pyruvic

acid/pyruvate acid.
▪ Occurs in cytoplasm of every living cell; all life on earth performs glycolysis.
▪ Anaerobic stage of cellular respiration.
o It does not require oxygen (O2) and does not yield much energy.

▪ Although it liberates only a small part of energy from glucose, it:

o Is important during severe muscular exercise, in which oxygen
supply is often insufficient to mee the demands of aerobic
metabolism.
o Provides all energy required by RBCs, as they lack mitochondria.

10 STEPS OF GLYCOLYSIS

FIRST HALF OG GLYCOLYSIS (ENERGY-REQUIRING STEPS)

▪ Preparatory phase
o Phosphorylation of glucose and its conversion to glyceroldehyde-3-
phosphate.

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1. The enzyme hexokinase phosphorylates (adds a phosphate group to) glucose
in the cell’s cytoplasm. In the process, a phosphate group from ATP is transferred
to glucose producing glucose 6-phosphate.

Glucose (C6H12O6) + hexokinase + ATP ADP + Glucose-6-Phosphate

(C6H13O9P)

2. The enzyme phospholglucoisomerase converts glucose-6-phosphate into its

isomer, fructose-6-phosphate. Isomers have the same molecular formula, but
the atoms of each molecule are arranged differently.

Glucose 6-Phosphate (C6H13O9P) + Phosphoglucoisomerase Fructose-6-

phosphate (C6H13O9P)

3. Phosphorylation of fructose-6-phosphate. Another ATP molecule is used by the

enzyme phosphofructokinase to transfer a phosphate group to fructose-6-
phosphate to form fructose-1, 6-biphosphate.

Fructose-6-phosphate (C6H13O9P) + phosphofructokinase + ATP ADP +

Fructose 1, 6-biphosphate (C6H14O12P2)

4. The newly high-energy phosphates further destabilize fructose-1, 6-

biphosphate. The enzyme aldolase splits fructose 1, 6-biphosphate into two
sugars that are isomers to each other. These two sugars are dihydroxyacetone
phosphate and glyceraldehyde phosphate.

Fructose 1, 6-biphosphate (C6H14O12P2) + aldolase dihydroxyacetone

phosphate (C3H7O6P) + Glyceraldehyde phosphate (C3H7O6P)

5. An isomerase transforms the dihydroxyacetone-phosphate into its isomer,

glyceraldehyde-e-phosphate. Hence, the pathway will continue with two
molecules of a single isomer. Glyceraldehyde 3-phosphate is removed as soon
as it is formed to be used in the next step of glycolysis.

Dihydroxyacetone phosphate (C3H7O6P) → Glyceraldehyde-3-phosphate

(C3H7O6P)

Net result for steps 4 and 5:

▪ Fructose 1, 6-bisphosphate (C6H14O12P2) ↔ 2 molecules of
glyceraldehyde-3-phosphate (C3H7O6P)

Two ATP molecules were used during the first half of glycolysis in the
phosphorylation of glucose, which is then split into two three-carbon molecules.

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SECOND HALF OF GLYCOLYSIS (ENERGY-RELEASING STEPS)
▪ Glyceraldehyde-3-phosphate is converted into pyruvate and the
formation of two ATP molecules and two NADH molecules.
▪ The three-carbon sugar molecules will proceed through the second half
of the pathway, and sufficient energy will be extracted to pay back the
two molecules used as initial investment, producing two additional ATP
molecules and even higher-energy, two NADH molecules.

6. In this step, the enzyme triose phosphate dehydrogenase serves two

functions:
a. First, the enzyme transfers a hydrogen (H-) from glyceraldehyde
phosphate to the oxidizing agent nicotinamide adenine dinucleotide
(NAD+), forming NADH.
b. Then, triose phosphate dehydrogenase adds a phosphate (P) from the
cytosol to the oxidized glyceraldehyde phosphate to form 1, 3-
bisphosphoglycerate. This occurs for both molecules of glyceraldehyde 3-
phosphate produced in step 5.

A. Triose phosphate dehydrogenase + 2 H- + 2 NAD+ → 2 NADH + 2 H+

B. Triose phosphate dehydrogenase + 2 P + 2 glyceraldehyde 3-phosphate
(C3H7O6P) → 2 molecules of 1,3-bisphosphoglycerate (C3H8O10P2)

If NAD+ is not available, the second half of glycolysis slows down or stops. If oxygen
is available, the NADH will be oxidized readily, producing ATP. whereas in
environment without oxygen, an alternate pathway (fermentation) can provide
the oxidation of NADH to NAD+. (Rye, et.al, 2017)

7. The enzyme phosphoglycerate kinase transfers a P from 1,3-

bisphosphoglycerate to a molecule of ADP, forming ATP. This happens for each
molecule of 1,3-bisphosphoglycerate. The process yields two 3-
phosphoglycerate molecules and two ATP molecules.

2 molecules of 1,3-bisphoshoglycerate (C3H8O10P2) + phosphoglycerokinase + 2

ADP → 2 molecules of 3-phosphoglycerate (C3H7O7P) + 2 ATP

8. The enzyme phosphoglyceromutase relocates the P from 3-phosphoglycerate

from the third carbon to the second carbon, forming 2-phosphoglycerate (an
isomer of 3-phosphoglycerate).

2 molecules of 3-Phosphoglycerate (C3H7O7P) + phosphoglyceromutase → 2

molecules of 2-Phosphoglycerate (C3H7O7P)

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9. The enzyme enolase removes a molecule of water from 2-phosphoglycerate,
forming phosphoenolpyruvate (PEP). This happens for each molecule of 2-
phosphoglycerate.

2 molecules of 2-Phosphoglycerate (C3H7O7P) + enolase → 2 molecules of

phosphoenolpyruvate (PEP) (C3H5O6P)

10. The last step in glycolysis. The enzyme pyruvate kinase transfers a P from PEP
to ADP, forming pyruvate and ATP. This happens for each molecule of
phosphoenolpyruvate. This reaction yields 2 molecules of pyruvate and 2 ATP
molecules.

2 molecules of phosphoenolpyruvate (C3H5O6P) + pyruvate kinase + 2 ADP → 2

molecules of pyruvate (C3H3O3-) + 2 ATP

OUTCOME OF GLYCOLYSIS:
2 molecules of pyruvate
2 molecules of ATP
2 molecules of NADH
2 molecules of water

Glycolysis produced 4 molecules of ATP, but two ATP molecules were used during
the first half of the pathway.

TRANSITION REACTION:THE OXIDATION OF PYRUVATE TO FORM ACETYL COA FOR

ENTRY INTO THE KREBS CYCLE
▪ This serves as a bridge connecting glycolysis with the Krebs cycle
▪ Takes place in the matrix of the mitochondrion.
▪ The acetyl coenzyme A is the high energy molecule that enters the Krebs
cycle.

STEPS in the BREAKDWON OF PYRUVATE (Rye, et.al, 2017)

1. A carboxyl group is removed from pyruvate and released carbon dioxide. This
result to a two-carbon hydroxyethyl group bound to the enzyme, pyruvate
dehydrogenase. This is the first step of the six carbons from the original glucose
molecule to be removed. Note that this step proceeds twice since there are two
pyruvate molecules produced at the end of glycolysis. Hence, for every glucose
molecule that is metabolised, two of the six carbons will have been removed at
the end of both steps.

2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are
picked up by the NAD+, and is reduced to NADH. The high-energy electrons
from NADH will be used later to produced ATP.

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3. The enzyme-bound is transferred to CoA (coenzyme A), forming acetyl CoA –
this high energy molecule enters the Krebs Cycle.

Note: Whenever a carbon molecule is removed during the second stage of

glucose metabolism, it is bound to two oxygen atoms, generating carbon dioxide.
Carbon dioxide is one of the major end products of cellular respiration.

IN SUMMARY, THE TWO PYRUVATE MOLECULES FORMED IN GLYCOLYSIS WHEN

PROCESSED IN THE TRANSITION REACTION PRODUCES A TOTAL OF :
2 NADH's are generated
2 CO2 are released

II. THE KREBS CYCLE

▪ Oxidation of pyruvate.
▪ AKA as CITRIC ACID CYCLE since the first intermediate formed, citric acid
or citrate.
▪ TCA CYLE since citric acid or citrate and isocitrate are tricarboxylic acids.
▪ THE KREBS CYCLE, after Hans Krebs, who first discovered the steps in the
pathways in pigeon flight muscles in the 1930s.
• Occurs in the matrix of mitochondria.
• Goal: take pyruvate and put it into the Krebs cycle, producing NADH and
FADH2.

EIGHT STEPS OF KREB’S CYCLE

1: Synthesis of Citric Acid.

▪ This is the first step of the cycle catalyzed by citrate synthase, which is the
condensation of acetyl-CoA with oxaloacetate to form citrate Negative
feedback and the amount of ATP available control the rate of this reaction.
▪ The two-carbon acetyl group combines with a four-carbon oxaloacetate,
forming a six-carbon molecule of citrate. Since it is highly exergonic, this
step is irreversible.
▪ Negative feedback and the amount of ATP available control this reaction,
in which if there is a short supply of ATP, the rate increases and vice versa.

2: Dehydration of citrate
▪ This is a reversible reaction, where citrate loses one water molecule and
gains another as citrate is converted into its isomer, isocitrate.

3: Oxidation and Decarboxylation of isocitrate

▪ This reaction is catalyzed by the enzyme isocitrate dehydrogenase, where
isocitrate is oxidized, generating a five-carbon molecule, -ketoglutarate,
together with CO2 molecule and two electrons that reduce NAD+ to NADH.

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▪ These are first NADH molecules produced in the cycle and CO2. The
enzyme catalyzing this step, isocitrate dehydrogenase, is also important in
regulating the speed of the citric acid cycle.

4: Oxidative decarboxylation of -ketoglutarate to Succinyl-CoA and CO2

▪ This is another oxidative decarboxylation step, in which -ketoglutarate is
converted to succinyl-CoA by the action of -ketoglutarate
dehydrogenase complex, releasing electrons that reduce NAD+ to NADH
and release carboxyl groups that forms molecules of CO2.
▪ This reaction produces the second CO2 and the second NADH of the cycle.
The coenzymes that are required in the reaction are thiamine
pyrophosphate, lipoic acid, FAD (Flavin Adenine Dinucleotide), NAD+ and
CoA.

5: Conversion of Succinyl-CoA to Succinate

▪ A phosphate group is substituted for coenzyme A, forming a high-energy
bond. This energy is used during the conversion of the succinyl group to
succinate, producing either guanine triphosphate (GTP) or ATP. GTP can
be converted to ATP.
▪ This reaction is catalyzed by the enzyme succinyl-CoA synthetase or
succinic thiokinase.

6: Oxidation of Succinate to Fumarate

▪ This reaction is catalyzed by the enzyme succinate dehydrogenase, in
which succinate is converted into fumarate. Two hydrogen atoms are
transferred to flavin adenine dinucleotide (FAD), generating FADH2.
▪ In this reaction the final electron acceptor is the FAD coenzyme. This
reaction yields two ATP molecules from the electron transport chain.

7: Hydration of Fumarate to Produce Malate

▪ The hydration reaction is catalyzed by the enzyme fumarase. The fumarate
is hydrated, producing Malate.

8: Oxidation of Malate to Oxaloacetate

▪ This is the final point of entry to the electron transport chain. Malate is
converted to oxaloacetate in a reaction catalyzed by malate
dehydrogenase. This reaction reduces nicotinamide adenine dinocleutide
(NAD+) molecule to NADH + H+.
▪ This reaction generates the NADH and oxaloacetate.

THE KREBS CYCLE

• 6 NADH 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 are released (2 per Acetyl CoA that enters)

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III. ELECTRON TRANSPORT PHOSPHORYLATION (CHEMIOSMOSIS)
▪ The last component of aerobic respiration and is the only part of glucose
metabolism that uses atmospheric oxygen. (Rye, et.al, 2017)
▪ Goal: to break down NADH and FADH2, pumping H+ into the outer
compartment of the mitochondria.
▪ Occurs in the mitochondria.
▪ ATP is generated as H+ moves down its concentration gradient through a
special enzyme called ATP synthase.
▪ It is a series of electron transfer from NADH and FADH2 to oxygen that
occurs in the inner membrane of mitochondria and coupled to the
generation of proton motive force – the energy stored in the
electrochemical proton gradient is then used for ATP synthesis by the F0F1-
ATP synthase or ATP synthetase.
▪ The reactions in the glycolytic pathway and citric acid cycle result in the
conversion of one glucose molecule to 6 CO2 molecules and the
concomitant reduction of 10 NAD+ to 10 NADH molecules and 2 FAD to
FADH2 molecules.
▪ 4 distinct multiprotein complexes:
o Complex I (NADH-Co Q reductase or NADH dehydrogenase)
o Complex II (succinate-Q-reductase)
o Complex III (cytochrome reductase, cytochrome b-c-1 complex
o Complex IV (cytochrome oxidase) as well as two mobile elements
coenzyme Q and cytochrome C.
STEPS
1. Complex I.
▪ Two electrons are carried to the first complex aboard NADH, consisting of
consisting of flavin mononucleotide (FMN) and an iron-sulfur (Fe-S)-
containing protein. FMN, which is derived from vitamin B2 (riboflavin) is one
of several prosthetic groups or co-factors in the electron transport chain.
When we say prosthetic group, this is a non-protein molecule that is needed
for the activity of a protein.
▪ The enzyme in Complex I “NADH Dehydrogenase Complex” is a very large
protein that contains 45 amino acid chains.
▪ Four hydrogen ions are pumped across the membrane by Complex I from
the matrix into the intermembrane space. Hence, hydrogen ion gradient is
established and maintained between the two compartments separated
by the inner mitochondrial membrane.

2. Complex II
▪ Complex II directly receive electrons from FADH2, which does not pass
through Complex I. The compound that connects the first and second
complexes to the third is ubiquinone (Q), a lipid soluble and moves freely
through the hydrophobic part of the membrane.

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▪ When Coenzyme Q is reduced to quinol (QH2), it accepts electrons from
Complex I and II and transfers them to Complex III.
▪ Since FADH2 and Ubiquinone bypass the first complex, fewer ATP molecules
are made from the FADH2 electrons.

3. Complex III
▪ “Cytochrome Oxidoreductase”
▪ It is a multiprotein complex, having a Cytochrome b, another Fe-S protein,
and Cytochrome c 1 component. The cytochrome proteins have a
prosthetic group of heme – this heme molecule is similar to the heme of
hemoglobin, but instead of oxygen, it carries electrons. Consequently, as
the iron ion at its core passes the electrons, it is reduced and oxidized –
fluctuating between different oxidation states: Fe++(reduced) and
Fe+++(oxidized).
▪ Electrons are transferred from the quinol compound to the Cytochrome b
and Cytochrome c 1 respectively with shuttle of the iron in heme between
Fe++ and Fe+++ forms and the electrons are finally transferred to cytochrome
C (the second mobile constituent).Protons are pumped out of the matrix
too.
▪ Cytochrome c is a single electron carrier and collects electrons from
complex III and delivers it to complex IV. It has only one heme prosthetic
group.

4. Complex IV. Reduction of Oxygen

▪ “Cytochrome oxidase” that contains cytochromes a and a3
▪ This complex is composed of two heme groups (one in each of the two
cytochromes, a and a3) and three copper ions (a pair of CuA and CuB in
cytochrome a3)
▪ The cytochromes hold an oxygen molecule very tightly between the iron
and copper ions until the oxygen is reduced completely. The reduced
oxygen then picks up two hydrogen ions from the surrounding medium,
producing water (H2O).
▪ The removal of hydrogen from the system contributes to the ion gradient to
be used in the process of chemiosmosis. (Rye, et.al, 2017)

Chemiosmosis
▪ In chemiosmosis, the free energy released from the series of redox reaction
is used in pumping hydrogen ions (protons) across the membrane. Due to
hydrogen ions’ positive charge and their aggregation on one side of the
membrane, both concentration and electrical gradients (electrochemical
gradient) are established.
▪ If hydrogen ions open the membrane to diffusion, the ions would tend to
diffuse back across into the matrix, propelled by their electrochemical
gradient. Remember that many ions cannot diffuse through the nonpolar
regions of phospholipid membranes without using ion channels.

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▪ Likewise, hydrogen ions in the matrix space can only pass through the inner
mitochondrial membrane with the aid of an integral membrane protein
called ATP synthase.
▪ ATP synthase acts as a tiny generator, turned by the force of hydrogen ions
that diffuses through it, down their electrochemical gradient.
▪ The turning of parts of this molecular machine facilitates the addition of ADP
to form ATP, using the potential energy of the hydrogen ion gradient.
▪ The ATP synthase is a complex molecular machine uses proton (H+) gradient
in forming ATP from ADP and inorganic phosphate (Pi).

SUMMARY:
Electron Transport Phosphorylation:
2 NADH from glycolysis = 6 ATP
2 NADH from transition reaction = 6 ATP
6 NADH from Krebs cycle = 18 ATP
2 FADH2 from Krebs cycle = 4 ATP
34 ATP

Energy Yield of Cellular Respiration:

Glycolysis: 2 ATP
Krebs Cycle: 2 ATP
ETC: 34 ATP
- 2 For NADH Transport
36 ATPs

Theoretically, one glucose molecule yields 36 ATPs, mostly from the electron
transport chain.

IV.ANAEROBIC RESPIRATION
▪ Metabolism without oxygen, and is the only way to generate NAD+
▪ Occurs in the cytoplasm of the cell
▪ Reduce pyruvate; thus generating NAD+

Fermentation
▪ This is a process in which it uses an organic molecule to regenerate NAD+
from NADH.
▪ For organisms that use fermentation, glycolysis still produce two ATPs, tow
NADHs, and two molecules of pyruvate from a glucose molecule.
However, pyruvate is not further oxidized and NADH does not donate its
electrons to an electron transport chain.

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a. ALCOHOL FERMENTATION
▪ Occurs in yeasts in many bacteria, producing ethanol, an alcohol.
▪ The first reaction is catalyzed by pyruvate decarboxylase with coenzyme
of thiamine pyrophosphate (TPP), removing carboxyl group from pyruvic
acid, releasing carbon dioxide as gas.
▪ Due to the loss of carbon dioxide, the size of the molecule by one carbon
is reduced, creating acetaldehyde.
▪ The second reaction is catalyzed by alcohol dehydrogenase oxidizing
NADH to NAD+ and reducing acetaldehyde to ethanol.
▪ The ethanol found in alcoholic beverages is produced by the
fermentation of pyruvic acid by yeast. The ethanol tolerance of years is
variable, ranging from about 5-21% and depends on the strain of yeast
and environmental conditions.

Pyruvic Acid CO2 + acetaldehyde + NADH ethanol + NAD+

b. LACTIC ACID FERMENTATION

▪ A fermentation method utilised by animals, and certain bacteria. For
example, the bacterium Lactobacillus ferments lactose in milk, producing
lactic acid – giving yogurt its sour taste.
▪ Physiologically occurs in red blood cells (no mitochondria) and in skeletal
muscles that lacks oxygen supply to allow aerobic respiration to continue
(i.e. in muscles used to the point of fatigue).
▪ The accumulation of lactic acid in muscles must be removed by the
blood circulation and the liver cells convert lactate back to pyruvate
(after exercise).
▪ The enzyme used in this reaction is lactate dehydrogenase. The cell uses
NADH to reduce pyruvate, producing NAD+ and lactic acid (or its close
relative, lactate).

Pyruvic Acid + NADH > lactic acid + NAD+

▪ The only goal of fermentation reactions is to convert NADH to NAD+ to be

used in glycolysis.
▪ No energy gained.
▪ Note the differences: Anaerobic respiration produces 2 ATPs from glycolysis,
whereas aerobic respiration produces 36 ATPS from glycolysis, Krebs cycle, and
oxidative phosphorylation (electron transport chain).
▪ Therefore, the evolution of an oxygen-rich atmosphere that facilitated the
evolution of aerobic respiration was crucial in the diversification of life.

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V.GLUCONEOGENESIS
▪ This is the synthesis of glucose from amino acids, pyruvate, lactate, or
glycerol.
▪ It occurs primarily in the liver when supply of blood glucose is low such as
when fasting, starvation, or low carbohydrate diet. Recall that our brain
uses ONLY glucose as its source of energy; thus, it is important that our
body maintain a minimum concentration of our blood glucose.
▪ Gluconeogenesis is not simply the reverse of glycolysis.

GLUCONEOGENESIS PATHWAY
▪ After eating, the body immediately starts to break the glucose down into
energy. However, if too much has been broken down into pyruvate, then
the process will be reversed to change it back into glucose for storage.
▪ Remember, the brain needs glucose as its sole source of energy, yet the
body is only able to store a few hours' worth of glucose. Once the body
signals that it is getting low in glucose stores, it starts to turn protein into
glucose.
▪ Fat and protein can be turned into oxaloacetate, one of the
intermediates in gluconeogenesis. The oxaloacetate can then be
converted into glucose. Fats cannot be used as a source of glucose. For
fat to be converted into oxaloacetate, a pyruvate is required.

VI. GLYCOGENESIS
▪ The synthesis of glycogen from glucose.
▪ Through this process, the body stores glucose (in the liver), creating
glycogen to be used later when the body does not have readily available
glucose.
▪ Glucose is modified and gains the ability to be stored in long chains –
glycogen.
▪ Key enzyme of glycogenesis is glycogen synthase

VII.GLYCOGENOLYSIS
▪ This is the process in which glycogen molecule is broken down into
glucose – a simple sugar used by our cells in producing energy.
▪ Glycogen is essentially stored energy in the form of long chain of glucose
and through phosphorolysis, glucose molecules are removed from the
chain. Phosphorolysis is the breaking down of molecular bond by adding
phosphoric acid.
▪ To removed multiple glucose molecules from the chain, glycogenolysis
occurs several times.
▪ Key enzyme of glycogenolysis is glycogen phosphorylase

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LIVER GLYCOGEN:
▪ Forms 8-10% of the wet weight of the liver
▪ Maintains blood glucose (especially between meals)
▪ Liver glycogen is depleted after 12-18 hours fasting
MUSCLE GLYCOGEN:
▪ Forms 2% of the wet weight of muscle
▪ Supplies glucose within muscles during contraction
▪ Muscle glycogen is only depleted after prolonged exercise

FOUR IMPORTANT FACTORS IN REGULATING BLOOD GLUCOSE LEVEL:

A. GASTROINTESTINAL TRACT:
▪ It controls the rate of glucose absorption
▪ The maximum rate of glucose absorption is 1 gm/kg body weight/ hour
▪ Glucose given orally stimulates more insulin than intravenous glucose. This
may be due to secretion of glucagon-like substance by intestines. This
stimulates B-cells of pancreas to secrete more insulin called anticipatory
action.

B. LIVER:
▪ The main blood glucose state.
▪ Maintains blood glucose level within normal as follows:
1. If blood glucose level increases, the liver controls this elevation and
decreases it through:
▪ Oxidation of glucose via major and minor pathways
▪ Glycogenesis
▪ Lipogenesis

2. If blood glucose level decreases, the liver controls this drop and increases it
through:
▪ Glycogenolysis
▪ Gluconeogenesis

C. KIDNEY:
▪ All glucose in blood is filtered through the kidneys, it then completely
returns to the blood by tubular reabsorption.
▪ If blood glucose exceeds a certain limit (called renal threshold), it will pass
in urine causing glucosuria.
▪ Renal threshold: it is the maximum rate of reabsorption of glucose by the
renal tubules.
▪ Normally the renal threshold for glucose is 180 mg/100mL

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D. HORMONES:
a. Insulin (the only hypoglycemic hormone):
Action of insulin:
▪ Insulin decreases blood glucose level by:
1. oxidation of glucose
2. glycogenesis
3. glycogenolysis
4. gluconeogenesis
5. lipogenesis

b. Anti-Insulin Hormones: (hyperglycemic hormones):

▪ Growth Hormone:
o It elevates the blood glucose level by stimulating gluconeogenesis
▪ Thyroxine:
o It elevates the blood glucose level by:
a. Increasing the rate of absorption of glucose from intestines.
b. Stimulating gluconeogenesis and glycogenolysis.
c. Inhibiting glycogenesis
▪ Epinephrine (adrenaline):
o It increases the blood glucose level by increasing glycogenolysis in
both liver and muscles
▪ Glucagon:
o It increases the blood glucose level by increasing glycogenolysis in
liver only.

ABNORMALITIES OF BLOOD GLUCOSE LEVEL

a.Hyperglycemia: (Diabetes Mellitus)

▪ It is an abnormal increase in blood glucose concentration due to
decrease insulin secretion and/or hypersecretion of anti-insulin hormones.
▪ If left untreated, hyperglycemia can become severe and lead to serious
complications requiring emergency care, such as diabetic coma.
▪ Persistent hyperglycemia in the long run, if not severe, can lead to
complications affecting your eyes, kidneys, nerves, and heart.

DIABETES MELLITUS
1. Type 1 Diabetes Mellitus
▪ Previously known as Insulin-Dependent Diabetes Mellitus (IDDM) and
usually develops among people younger than age 20.
▪ This occurs when the person’s immune system attacks the beta cells of the
pancreas, resulting to little or no insulin produced by the pancreas.
▪ The cellular metabolism of an untreated type 1 DM is similar to that of a
starving person. Because of lack/absence of insulin that would help the
entry of glucose into our cells, fatty acids will now be used by most cells to
produce ATP. Hence, the stores of triglycerides in our adipose tissues are

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catabolized to produce fatty acids and glycerol – and the by-products of
the breakdown of fatty acids are organic acids known as KETONES or
KETONE BODIES. The building up of ketones causes our blood pH to fall – a
condition known as KETOACIDOSIS. If left untreated, it can result to death.

2. Diabetes Mellitus 2
▪ Previously known as Non-Insulin-Dependent Diabetes Mellitus (NIDDM),
and much more common than type 1.
▪ It often occurs among obese people who are over age 35, although the
number of obese children and teenager with type 2 diabetes is
increasing.
▪ This type of diabetes is not caused by the shortage of insulin, but because
the target cells become less sensitive to insulin because of down-
regulation of receptors of insulin.
▪ High glucose levels can be controlled by diet, regular exercise, and
weight loss.

b. Hypoglycemia:
▪ Low blood glucose level, due to excess insulin that stimulates too much
uptake of our body cells of glucose.
▪ Hypoglycemia stimulates the secretion of epinephrine, glucagon, and
human growth hormone, causing anxiety, sweating, hunger, tremor,
increase heart rate and weakness.
▪ When glucose level in our blood decreases, our brain cells are also
deprived of a steady supply of glucose.
▪ Severe hypoglycemia causes mental disorientation, convulsions,
unconsciousness, and shock. Shock caused by insulin overdose is called
insulin shock. Death can occur quickly unless blood glucose levels is
restored to normal.
Causes:
a. Excessive insulin:
▪ Overdose of insulin
▪ Tumor of B-cells of pancreas (insulinoma)
b. Hyposecretion of anti-insulin hormones:
▪ Hypofunctions of the pituitary gland, adrenals & thyroid gland.
▪ Insulin acts unopposed causing lowering of blood glucose.
c. Liver disease:
• Hypoglycemia is due to decreased glycogen storage and impaired
gluconeogenesis

A diabetic suffering from either a hyperglycemia or a hypoglycemia can have

very similar symptoms – mental changes, coma, seizures, and so on. It is important
to quickly and correctly identify the cause of the underlying symptoms and treat
them appropriately. (Tortora G. and Derrickson, B., 2014)

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REFERENCES:

Lehninger, A., et.al. (1993). Principles of Biochemistry (2nd). New York. Worth
Publishers.

Rye, C., et.al. (2017). Biology. https://openstax.org/details/books/biology-2e

Tortora, G. and Derrickson, B. (2014). Principles of Anatomy and Physiology (14th).

NJ. John Wiley & Sons

Bentadan, M.C. (n.d.). Biochem Module

Carbohydrate Metabolism (n.d.).

https://opentextbc.ca/anatomyandphysiology/chapter/24-2-carbohydrate-
metabolism/

Demczko, M. (2020 April). Glycogen Storage Diseases.

https://www.msdmanuals.com/professional/pediatrics/inherited-disorders-of-
metabolism/glycogen-storage-diseases

Glycogenesis. (2019 April 17). https://biologydictionary.net/glycogenesis/

Glycogenolysis. (2017 April 28). https://biologydictionary.net/glycogenolysis/

Hechanova, L.A. (2020 July). Renal Glucosuria.
https://www.msdmanuals.com/professional/genitourinary-disorders/renal-
transport-abnormalities/renal-glucosuria

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