BIOCHEM NOTES

METABOLISM IMPORTANT INTERMEDIATE COMPOUNDS: SUMMARY

Int. compounds Definition Other notes
CONCEPTS
Adenosine o Monophosphate (AMP)
Term Definition Other notes Phosphates o Diphosphate (ADP)
Metabolism chemical reactions done by living Catalyzed by enzymes o Triphosphate (ATP)
organism o Cyclic monophosphate (cAMP)
Catabolism breakdown of substances by an important catabolic Flavin Adenine o Flavin subunit is the active form –
organism; larger molecules reactions occur in the Dinucleotide accepts and donates electrons
mitochondria (FAD) o Ribitol is reduced form of ribose
Anabolism synthesis of molecules used to Nutrients are converted; sugar
build molecules for cell growth small molecules + energy Nicotinamide
and multiplication adenine
Metabolic series of consecutive biochemical Has 2 types: dinucleotide
pathway reactions used to convert a → Linear (NAD)
starting material into an end → Cyclic Coenzyme A o Derivative of Vit. B
product o Acetyl-CoA (acetylated)
* Cells usually employ different chemical reactions for the breakdown and
synthesis of the same molecule. ADENOSINE PHOSPHATE GRPS
Classification Definition Other notes
METABOLISM AND CELL STRUCTURE AMP Structural component of RNA
Prokaryotic cell Eukaryotic cell ADP & ATP Key component of metabolic Phosphate groups are connected
→ single compartment → multi-compartment cell pathways to AMP by strained bonds which
organism → DNA is present in the membrane require less than normal energy to
→ no nucleus (only in bacteria) enclosed nucleus hydrolyze them
→ NUCLEOID. single circular → Cell is compartmentalized into cellular Nucleotide → URIDINE TRIPHOSPHATE (UTP). Carbohydrate metabolism
DNA molecule present near organelles Triphosphate → GUANOSINE TRIPHOSPHATE (GTP). Protein and
of the cell → 1,000x larger than bacterial cells carbohydrate metabolism
MITOCHONDRIA → CYTIDINE TRIPHOSPHATE (CTP). Lipid metabolism
Definition Other notes
→ responsible for Layers of the membrane:
the generation of Inner Outer
most of the Highly impermeable to Permeable to small
energy for a cell most substances: molecules
→ synthesis of ATP 50% lipid, 50% protein 20% lipid, 80% protein
*Inner membrane folded to increase surface area.
 BIOCHEM NOTES
FLAVIN ADENINE DINUCLEOTIDE (FAD, FADH2) CLASSIFICATION METABOLIC INTERMEDIATE COMPOUNDS
Definition Other notes
coenzyme required in → Flavin subunit is the active form – accepts
numerous metabolic redox and donates electrons
reactions → Ribitol is reduced form of ribose sugar
→ typical cellular reaction in → FAD = oxidized form; FADH2 = reduced form
which FAD serves as → In enzyme reactions FAD goes back and
oxidizing agent involves forth (equilibrium) from oxidized to
conversion of an alkane to reduced form
alkene

NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD)

Definition Other notes FREE-ENERGY PHOSPHATES TABLE
A typical cellular reaction in → NAD+: coenzyme
which NAD+ serves as the → NADH reduced form
oxidizing agent is the → Nictotinamide – ribose – ADP
oxidation of a secondary → 6 subunit structure: Nicotinamide –
alcohol to give a ketone ribose – phosphate – phosphate – ribose
adenine

COENZYME A
Definition Other notes
coenzyme A is the → Three subunit structure
sulfhydryl group (-SH → ACETYL GROUP. the portion of an acetic
group) in the ethanethiol acid molecule (CH3-COOH) that remains
subunit of the coenzyme after the -OH group is removed from the
carboxyl carbon atom.
 BIOCHEM NOTES
METABOLISM CYCLE FULL INFROMATION PER STAGES
Stage Description
1 → Begins in the mouth (saliva contains starch digesting
Digestion enzymes), continues in the stomach (gastric juice),
completed in small intestines
→ The digestion products are absorbed into the blood and
transported to body’s cells
→ End Products of Digestion
o Glucose and monosaccharides from carbohydrates
o Amino acids from proteins
o Fatty acids and glycerol from fats and oils
2 → The small molecules from Stage 1 are further oxidized
Acetyl grp → End product of these oxidations is acetyl CoA
fromation → Involves numerous reactions:
o Reactions occur both in cytosol (glucose
metabolism) as well as mitochondria (fatty acid
metabolism) of the cells
3 → Takes place inside the mitochondria
Citric acid cycle → First intermediate of the cycle is citric acid – therefore
designated as Citric acid Cycle
→ In this stage, acetyl group is oxidized to produce 𝐶𝑂2 and
energy
→ The carbon dioxide we exhale comes primarily from this
stage
OVERVIEW: → Most energy is trapped in reduced coenzymes NADH and
Stage 𝐹𝐴𝐷𝐻2
1 Digestion → Some energy produced in this stage is lost in the form of
2 Acetyl grp formation heat
3 Citric acid cycle 4 → Takes place in mitochondria
4 Electron transport chain and oxidative phosphorylation Electron chain → NADH and 𝐹𝐴𝐷𝐻2 are oxidized to release H+ and
and oxidation electrons
phosphorylation → NADH and 𝐹𝐴𝐷𝐻2 are oxidized to release H+ and
electrons
→ Electrons are transferred to 𝑂2 and 𝑂2 is reduced to 𝐻2𝑂
→ Electrons are transferred to 𝑂2 and 𝑂2 is reduced to 𝐻2𝑂
→ ATP is the primary energy carrier in metabolic pathways
 BIOCHEM NOTES
CITRIC ACID CYCLE CITRIC CYCLE: SUMMARY
Definition Other notes
series of biochemical Also known as tricarboxylic acid (TCA) or Krebs cycle:
reactions in which the o Citric acid is a tricarboxylic acid
acetyl portion of o Named after Hans Krebs who elucidated this
acetyl CoA is oxidized pathway
to carbon dioxide and
the reduced Two important types of reactions:
coenzymes 𝐹𝐴𝐷𝐻2 o Oxidation of NAD+ and FAD to produce 𝐹𝐴𝐷𝐻2
and NADH are and NADH
produced o Decarboxylation of citric acid to produce CO2
o The citric acid cycle also produces 2ATP by
substrate level phosphorylation from GTP

Acetyl CoA + 3NAD + FAD + GDP +Pi + 2𝐻2𝑂 => 2𝐶𝑂2 + CoA-SH + 3NADH + 2H +
𝐹𝐴𝐷𝐻2 + GTP
 BIOCHEM NOTES
Step Description → Isocitrate is oxidized to a ketone (oxalosuccinate) by
1 NAD1, releasing two hydrogens.
Formation of → The oxalosuccinate remains bound to the enzyme and
Citrate undergoes decarboxylation (loses CO2), which produces
the C5 a-ketoglutarate (a keto dicarboxylate species)
4
Oxidation of a-
Catalyzed by: citrate synthase Ketoglutarate
→ The condensation of acetyl CoA and oxaloacetate to &Formation of
form citryl CoA CO2
→ Hydrolysis of the thioester bond in cityl CoA to produce
CoA-SH and citrate Catalyzed by: a-ketoglutarate dehydrogenase complex
→ Second redox reaction
2 → A second NAD+ is converted to its reduced form, NADH
Formation of → A second carboxyl group is removed as CO2
Isocitrate → Coenzyme A reacts with the decarboxylation product
succinate to produce succinyl CoA, a compound with
high-energy thioester bond

Catalyzed by: aconitase 5

→ Involves a dehydration, then hydration Thioesther
→ Citrate is a tertiary alcohol and isocitrate a secondary bond cleavage
alcohol. Tertiary alcohols are not readily oxidized; in succinyl CoA
secondary alcohols are easier to oxidize &
Phosphorylation
3 of GDP Catalyzed by: succinyl-CoA synthetase
Oxidation of → Succinyl CoA is converted to succinyl phosphate (a high-
Isocitrate & energy phosphate compound) = CoA-SH
Formation of → The phosphoryl group present in succinyl phosphate is
CO2 then transferred to GDP = GTP and succinate
→ Energy analysis: When broken, the high-energy
thioester bond in succinyl CoA releases energy, which is
Catalyzed by: isocitrate dehydrogenase trapped by formation of GTP
→ Involves redox (the first of four redox reactions in this → The function of the GTP produced is similar to that of
cycle), and decarboxylation ATP, which is to stare energy in the form of high-energy
→ Isocitrate is oxidized to a ketone (oxalosuccinate) by phosphate bond
NAD1, releasing two hydrogens.
 BIOCHEM NOTES
6 KEYNOTES IN CITRIC CYCLE
Oxidation of 1. The “fuel” for the cycle is acetyl CoA, obtained from the breakdown of
Succinate carbohydrates, fats, and proteins.
2. Four of the cycle reactions involve oxidation and reduction. The oxidizing
agent is either NAD1 (three times) or FAD (once). The operation of the cycle
Catalyzed by: succinate dehydrogenase depends on the availability of these oxidizing agents.
→ Oxidizing agent: FAD 3. In redox reactions, NAD1 is the oxidizing agent when a carbon–oxygen
→ FAD is reduced to 𝐹𝐴𝐷𝐻2 double bond is formed; FAD is the oxidizing agent when a carbon–carbon
→ Two hydrogen atoms are removed from the succinate double bond is formed.
to produce fumarate 4. The three NADH and one FADH2 that are formed during the cycle carry
7 electrons and H1 to the electron transport chain through which ATP is
Hydration of
synthesized.
Fumarate
5. Two carbon atoms enter the cycle as the acetyl unit of acetyl CoA, and two
carbon atoms leave the cycle as two molecules of CO2. The carbon atoms
that enter and leave are not the same ones. The carbon atoms that leave
Catalyzed by: fumarase during one turn of the cycle are carbon atoms that entered during the
→ Catalyzes the addition of water to the double bond of previous turn of the cycle.
fumerate 6. Four B vitamins are necessary for the proper functioning of the cycle:
→ The enzyme is stereospecific, so only L isomer of the
riboflavin (in both FAD and the a-ketoglutarate dehydrogenase complex),
product malate is produced
8 nicotinamide (in NAD1), pantothenic acid (in CoA—SH), and thiamine (in
Oxidation of the a-ketoglutarate dehydrogenase complex).
L-malate to 7. One high-energy GTP molecule is produced by phosphorylation.
Regenerate
Oxaloacetate REGULATION OF CITRIC ACID CYCLE
 The rate at which the citric acid cycle operates is controlled by ATP and
Catalyzed by: malate dehydrogenase
→ Fourth redox reaction NADH levels
→ A molecule of NAD+ reacts with malate, picking up  When ATP supply is high, ATP inhibits citrate synthase (from step 1)
two hydrogen atoms with their associated energy  When ATP levels are low, ADP activates citrate synthase
form NADH+ H+  Similarly, ADP and NADH control isocitrate hydrogenase:
→ Product: regenerated oxaloacetate, which can o NADH acts as inhibitor
combine with another acetyl CoA
o ADP as an activator

ELECTRON TRANSPORT CHAIN
Definition
→ Facilitates the passage of
electrons trapped in 𝐹𝐴𝐷𝐻2
and NADH during citric acid
cycle
→ ETC. series of biochemical
reactions in which
intermediate carriers (protein
and non-protein) aid the
transfer of electrons and
hydrogen ions from NADH and
𝐹𝐴𝐷𝐻
→ 2 hydrogen ions, 2 electrons
and ½ oxygen molecule react
to form the product water
→ Two mobile electron carriers
are: Coenzyme Q and
cytochrome C.
Other notes
→ The ultimate receiver of electrons is
molecular oxygen
→ The electron transport (respiratory
chain) get its name form the fact
electrons are transported to oxygen
absorbed via respiration.
→ Energy is used to synthesize ATP in
oxidative phosphorylation
The energy released is coupled with the
formation of three ATP molecules per
every molecule
NADH processed through ETC.
The reaction releases energy
(exothermic reaction)
→ The enzymes and electron carriers
needed for the ETC are located along
the inner mitochondrial membrane
BIOCHEM NOTES
Cythochrome C- → Cytochrome is a heme iron protein in which
reductase reversible oxidation of an iron atom occurs
→ Various cytochromes (cyt a, cyt b, cyt c) differ from
each other by:
a. protein constituents
b. manner in which the heme is bonded to the
protein;
c. attachment to heme rings
Complex 4: → has 13 subunits including two cytochromes
Cytochrome C- → electrons flow from cyt c - cyt a – ct a3
oxidase → final stage of electron transfer, the electrons from
cyt a3, and hydrogen ion (H+) combine with oxygen
(O2) to form water
𝑂2 + 4𝐻+ + 4𝑒− => 2𝐻2𝑂
→ 95% of the oxygen used to cells serves as the final
electron acceptor for the ETC

COMPLEXES OF TRANSPORT CHAIN

Complex Definition
Complex 1: NADH- → NADH from citric acid cycle is the source of
enzyme Q- electrons for this complex
reductase → Has >40 subunits including flavin mononucleotide
(FMN) and several iron-sulfur protein clusters (FeSP)
→ Facilitates transfer of electrons from NADH to
coenzyme Q
Complex 2: → Smaller than complex 1; succinate is converted to
Succinate- fumerate by this complex
coenzyme Q- → only four subunits including two ironsulfur protein
reductase clusters (FeSP)
→ generates 𝐹𝐴𝐷𝐻2 ; CoQ is the final recipient of the
electrons from 𝐹𝐴𝐷𝐻2 Complexes I, III, and IV of ETC chain have a second function in which they serve as
Complex 3: → Has 11 different subunits “proton pumps”, transferring protons from the matrix side of the inner mitochondrial
Coenzyme Q- → Several iron-sulfur proteins and cytochromes are membrane to the intermembrane space.
electron carriers in this complex
 BIOCHEM NOTES
OXIDATIVE PHOSPHORYLATION NON-ETC OXYGEN-CONSUMING RXNS
Definition Other notes Definition Other notes
Process by which ATP COUPLED REACTIONS. pairs of biochemical reactions → > 90% of inhaled oxygen via → ROS are both beneficial and
is synthesized from that occur concurrently in which energy released by respiration is consumed during problematic in the body:
ADP and P, using the one reaction is used in the other reaction oxidative phosphorylation o Benefits: White blood cells
energy released in the coupling of ATP synthesis with the reactions of the ETC → Remaining O2 are converted produce a significant amount of
ETC – coupled is related to the movement of protons (H+ ions) across to several highly reactive superoxide free radicals via the
reactions the inner mitochondrial membrane. oxygen species (ROS) with in following reaction to destroy the
the body. invading bacteria and viruses.
a. Hydrogen peroxide (𝐻2 → > 95% of the ROS formed are quickly
𝑂2) converted to nontoxic species in the
b. Superoxide ion (𝑂2) following reactions
c. Hydroxyl radical (OH)
*Superoxide ion and hydroxyl
radicals have unpaired electron
and are extremely reactive.
→ ROS can also be formed due to → About 5% of ROS escape destruction by
external influences such as superoxide dismutase and catalase
polluted air, cigarette smoke, enzymes
and radiation exposure → Antioxidants present in the body:
→ Antioxidants molecules Vitamin K, C, Glutathione (GSH), Beta-
present in the body help trap carotine
ROS species → Plant products such as flavonoids are
ATP ADDITIONAL NOTES also good antioxidants
ATP production for common Importance of the ATP
metabolic pathway B VITAMIN AND METABOLIC PATHWAY
Formation of ATP accompanies the → ATP is a high-energy phosphate Vitamin B Metabolic pathway involved
flow of protons from the compound Niacin NAD+ and NADH
intermembrane space back into the → Hydrolysis to ADP produces an Riboflavin FAD, FADH2+, and FMN
mitochondrial matrix intermediate amount of free Thiamin TPP
→ Proton flow results from an energy Pantothenic acid CoA
electrochemical gradient across → The energy derived from ATP
the inner mitochondrial hydrolysis is a biochemically
membrane useful amount of energy
o 1 NADH mole = 2.5 ATP
o 1 FADH2 mole = 2.5 ATP
o 1 GTP mole hydrolyzed = 1
ATP
 BIOCHEM NOTES
METABOLISM: CARBOHYDRATES GLYCOLYSIS: FLOW SUMMARY

DIGESTION OF CARBOHYDRATES
Description Other notes
Carbohydrates, especially During carbohydrate digestion, disaccharides and
glucose, play major roles polysaccharides are hydrolyzed to form
in cell metabolism monosaccharides, primarily glucose, fructose and
galactose

BLOOD SUGAR LEVELS

Hypoglycemia
blood sugar levels are below normal
fasting level
→ Mild hypoglycemia = dizziness and
fainting as brain cells are deprived
of energy.
→ Severe hypoglycemia = convulsions
and shock.
Hyperglycemia
blood sugar levels are above than
normal fasting level
→ Blood glucose above about 180
mg/100 ml
GLUCOSURIA. blood glucose level at
which this occurs is the renal
threshold

GLYCOLYSIS: PATHWAY
Description
→ Net result of converting a
glucose molecule into two
molecules of pyruvate
→ Net gain of 2 moles of ATP for
every mole of glucose that is
converted to pyruvate
BIOCHEM NOTES
o When ATP concentrations are low, ADP and AMP concentrations are
Other notes high, which activates the phosphofructokinase, accelerating the
→ All the enzymes in the glycolysis glycolysis pathway.
pathway are found in cellular
cytoplasm THE SIX-CARBON STAGE OF GLYCOLYSIS
→ Other sugars are also digested in Steps Description
glycolysis: Step 1 Formation of Glucose 6-Phosphate
o Fructose enters glycolysis as Phosphorylation
dihydroxyacetone phosphate and using ATP
glyceraldehyde- 3- phosphate
o Galactose is isomerized to form
glucose-6- phosphate

GLYCOLYSIS: ENZYMES REGULATION

Enzyme Catalyzes Inhibited/Activated o Hexokinase, an enzyme that requires Mg2+ ion for its
Hexokinase initiates the glycolysis Inhibited by a high activity, catalyzes the reaction.
pathway concentration of o first of two steps in which an ATP molecule is converted to
→ conversion of glucose to glucose-6- phosphate an ADP
glucose-6- phosphate (feedback inhibition) o Phosphorylation of glucose provides a way of “trapping”
Phosphofructokinase irreversible conversion of Inhibited by high glucose within a cell. Glucose can cross cell membranes,
fructose 6- phosphate to concentrations of ATP but glucose 6-phosphate cannot
1,6- biphosphate; allosteric and citrate, and o Phosphorylation of glucose changes it from a neutral
enzyme activated by high molecule to a negatively charged substance
concentrations of ADP Step 2 Formation of Fructose 6-Phosphate
and AMP Isomerization
Pyruvate kinase conversion of 3- Inhibited by high
phosphoenolpyruvate to concentrations of ATP.
pyruvate; allosteric enzyme
Additional notes:
During glycolysis pathway 1, the citric acid cycle and electron transport chain are
activated which produce large amounts of ATP.
o If ATP use decreases, the concentration of ATP decreases as well. The o Glucose 6-phosphate is isomerized to fructose 6-
ATP binds to phosphofructokinase and pyruvate kinase, slowing down phosphate by phosphoglucoisomerase
o Net result of this change is that carbon 1 of glucose is no
their activity, and thus slowing the glycolysis pathway
longer part of the ring structure.
o both sugars contain six carbon atoms
 BIOCHEM NOTES
Step 3 Formation of Fructose 1,6-Bisphosphate Step 6 Formation of 1,3-Bisphosphoglycerate
Phosphorylation Oxidation and
Using ATP Phosphorylation
Using Pi

o Similar to step 1
o Enzyme involved, phosphofructokinase, is another enzyme o catalyzed by glyceraldehyde 3-phosphate dehydrogenase,
that requires Mg 21 ion for its activity. The fructose a phosphate group is added to glyceraldehyde 3-
molecule now contains two phosphate groups phosphate to produce 1,3-bisphosphoglycerate
Step 4 Formation of Two Triose Phosphates o hydrogen of the aldehyde group becomes part of NADH
Cleavage o molecule of the reduced coenzyme NADH is a product of
this reaction and also that the source of the added
phosphate is inorganic phosphate (Pi)
Step 7 Formation of 3-Phosphoglycerate
Phosphorylation
of ADP

o The reacting C6 species is split into two C3 (triose) species

o One product is dihydroxyacetone phosphate, and the o the diphosphate species just formed is converted back to
other is glyceraldehyde 3-phosphate a monophosphate specie
o Aldolase is the enzyme that catalyzes this reaction o ATP-producing step in which the C-1 phosphate group of
Step 5 Formation of Glyceraldehyde 3-Phosphate 1,3-bisphosphoglycerate (the high-energy phosphate) is
Isomerization trans ferred to an ADP molecule to form the ATP.
o The enzyme involved is phosphoglycerokinase
o ATP production in this step involves substrate-level
phosphorylation
SUBSTRATE-LEVEL PHOSPHORYLATION. biochemical
process whereby ATP is produced from ADP through
direct transfer of a high-energy phosphoryl group
o Dihydroxyacetone phosphate converted into from a reaction substrate to ADP
glyceraldehyde 3-phosphate o involves production of ATP from ADP using Pi (free
o The isomerization process from ketose to aldose is phosphate) and the energy “harvested” from the
catalyzed by the enzyme triosephosphate isomerase oxidation-reduction reactions of the electron transport
chain
 BIOCHEM NOTES
Step 8 Formation of 2-Phosphoglycerate Additional Notes:
Isomerization → Steps 1 – 3 are “the energy-consuming stage”
→ Steps 4 – 10 are “the energy-generating stage”
→ ATP molecules are involved in Steps 1, 3, 7, and 10 of glycolysis
→ The overall net equation for the process of glycolysis is

o the phosphate group of 3-phosphoglycerate is moved

from carbon 3 to carbon 2
o enzyme phosphoglyceromutase catalyzes the exchange
of the phosphate group between the two carbons
Step 9 Formation of Phosphoenolpyruvate
Dehydration

→ Step 4 structural relationship of reactant and product

o an alcohol dehydration reaction that proceeds with the

enzyme enolase, another Mg2+ requiring enzyme
o result is another compound containing a high-energy
phosphate group
Step 10 Formation of Pyruvate
Phosphorylation
of ADP

o Phosphoenolpyruvate transfers its high-energy

phosphate group to an ADP molecule to produce ATP
and pyruvate
o Phosphoenolpyruvate transfers its high-energy
phosphate group to an ADP molecule to produce ATP
and pyruvate
2 C3 molecules are reacting, 2 ATP molecules are produced
 BIOCHEM NOTES
FRUCTOSE AND GALACTOSE IN
GLYCOLUSIS PATHWAY
 BIOCHEM NOTES
FATES OF PYRUVATE
Concepts Other notes
As the process occurs, NAD+ is reduced to 3 things that may occur to
NADH. The need for a continuous supply of pyruvate after glycolysis:
NAD+ for glycolysis is a key to understand the 1. Oxidation to acetyl CoA
fates of pyruvate under aerobic conditions
In each case, pyruvate is metabolized so as to 2. Reduction to lactate under
regenerate NAD+ allowing glycolysis to anaerobic conditions
continue 3. Reduction to ethanol under
anaerobic conditions for
some prokaryotic organisms

OXIDATION TO ACETYL COA ENERGY EFFICIENCY IN LIVING ORGANISMS

Concepts Other notes Concepts Other notes
Under aerobic conditions, pyruvate is oxidized NAD+ is regenerated when glucose oxidation liberates 686 kcal/mol, → Living cells can capture
in the mitochondria to form acetyl CoA: NADH transfers its electrons whereas the synthesis of 32 mol of ATP stores 34% of the released free
to O2 in the electron 234 kcal/mol. The efficiency of the energy energy and make it
transport chain; Some acetyl storage available to do
CoA serves as a starting biochemical work
NAD+ is regenerated when NADH transfers its material for fatty acid
→ Automobile engines make
electrons to O2 in the electron transport chain. biosynthesis
available 20-30% of the
Additional notes: energy actually released
The net overall reaction for processing one glucose molecule to two molecules of by burning gasoline
acetyl CoA is:
ATP TABLE IN EACH CATABOLIC STEP
Catabolic step Energy production
Glycolysis 2 NADH (cytoplasmic) – 2ATP -> liver, heart,
(1 glucose -> 2 pyruvates) kidneys = 5ATP -> brain, muscle = 3 ATP
Oxidation of 2 pyruvates to 2 2 NADH (mitochondrial) -> 5ATP
acetyl CoA
Citric acid cycle, one turn 3 NADH -> 7.5 ATP; 1 FADH -> 1.5 ATP; 1 GTP
-> 1 ATP = 10 ATP
Citric acid cycle, two turns 2 x 10 = 20 ATP
Total /glucose molecule 32 ATP (30 ATP)
 BIOCHEM NOTES
GLYCOGENESIS Step 3 Glucose Transfer to a Glycogen Chain
Concepts Other notes Linkage to o The glucose unit of UDP-glucose is then attached to the
→ Excess glucose is converted into glycogen in a Glycogen is stored Chain end of a glycogen chain
process called glycogenesis. primarily in the liver o Glucose-UDP is the activated carrier of glucose in
→ This anabolic process results in a bonding of glucose and muscle tissue, glycogen synthesis (glycogenesis)
units to a growing glycogen chain. The energy although some
provided by the hydrolysis of uridine triphosphate glycogenesis can
(UTP; uracil + ribose + three phosphates) occur in all cells.

STEPS IN GLYCOGENESIS
Steps Description
Step 1 Formation of Glucose 1-phosphate GLYCOGENOLYSIS
Isomerization o The starting material is glucose 6-phosphate
Concepts Other notes
o The enzyme phosphoglucomutase effects the change from
→ Metabolic pathway by which glucose 6-phosphate Two-step process
a 6-phosphate to a 1-phosphate
is produced from glycogen
→ does not require UTP or UDP molecules

STEPS IN GLYCOGENOLYSIS
Steps Description
Step 1 Formation of Glucose 1-phosphate
Phosphorolysis Enzyme glycogen phosphorylase effects the removal of an
Step 2 Formation of UDP-glucose end glucose unit from a glycogen molecule as glucose 1-
Activation The activator is the high-energy compound UTP (uridine phosphate
triphosphate). A UMP is transferred to glucose 1-phosphate,
and the resulting PPi is hydrolyzed to 2Pi

Step 2 Formation of Glucose 6-phosphate

Isomerization enzyme phosphoglucomutase catalyzes the isomerization
process whereby the phosphate group of glucose 1-
phosphate is moved to the carbon 6 position

Reverse of glycogenesis first step.


Final step, glucose 6-phosphate is hydrolyzed to free glucose GLUCONEOGENESIS
by the enzyme glucose 6- phosphatase (found only in liver, Concept
kidney and intestinal cells) → process of synthesizing glucose
from noncarbonate materials
→ The new enzymes for
gluconeogenesis are fructose 1,6-
bisphosphatase and glucose 6-
phosphatase
→ Gluconeogenesis involving lactate
is especially important under
anaerobic conditions
The overall net reaction for gluconeogenesis is
BIOCHEM NOTES
Other notes
The supply of glucose in the form of
liver and muscle glycogen can be
depleted by about 12-18 hours of
fasting, and in a shorter time as a
result of heavy work or strenuous
exercise. Nerve tissue, including the
brain, would be deprived of glucose if
the only source was glycogen.

Hence, 4 ATP and 2GTP is required to reconvert pyruvate to glucose

CORI CYCLE
Concept Other notes
Additional notes: → 90% of gluconeogenesis occurs in the liver CORI CYCLE. cyclic
→ Muscle cells lack glucose 6-phposphotase and cannot form free glucose from → During exercise, lactate levels increase in process if transport of
glycogen. muscle tissue, and some diffuses into the blood lactate from muscle to
→ lactate is transported to the liver, where lactate liver, the resynthesis of
o They carry out the first two steps in glycogenolysis to produce
dehydrogenase converts it back to pyruvate glucose by
glucose 6- phosphate
gluconeogenesis, and the
o This form of glucose is the first intermediate in the glycolysis
return of glucose to
pathway which produces energy muscle tissue.
o Muscles therefore only use glycogen for energy production.
→ The liver, glycogen is broken down all the way to form free glucose, which is
related into the blood during muscular activity and between meals.
o This glucose is used to maintain a relatively constants level of
blood glucose.
 BIOCHEM NOTES
o Increases the rate of synthesis of glycogen,
fatty acids and proteins
o Insulin stimulates glycolysis
blood glucose levels begin to decrease within one
hour, and return to normal in 3 hours
Glucagon polypeptide hormone (29 aa’s); made in the a-cells of
the pancreas
→ Activates the breakdown of glycogen in the liver,
thereby increasing blood glucose levels, thus
counteracting the effect of insulin
→ Insulin and glucagon work in opposition to each
other, and blood sugar levels depend in part of the
biochemical balance between these hormones
Epinephrine → Also known as adrenaline, hormone and
neurotransmitter
→ stimulates glycogen breakdown in muscles, and to a
smaller extent in the liver
→ Epinephrine also increases heart rate, constricts
blood vessels, and dilates air passages
→ Fight or flight response

B VITAMIN AND METABOLIC PATHWAY

Vitamin B Metabolic pathway
involved
Biotin enzyme pyruvate
carboxylate, the
enzyme needed to
REGULATION OF CARBOHYDRATE METABOLISM convert pyruvate to
oxaloacetate (the new
Regulatory hormones Description
first step in
Insulin → polypeptide hormone (51 aa’s); made in the b-cells
gluconeogenesis)
of the pancreas
Vitamin in the form of PLP is
→ When carbohydrates are consumed, blood glucose
B6 involved in
level rise, and the pancreas releases insulin into the
glycogenosis
bloodstream
o Enhances the absorption of glucose from the
blood into the cells of active tissues as skeletal
and heart muscles.
 BIOCHEM NOTES
GLUCOSE METABOLISM SUMMARY
 BIOCHEM NOTES
METABOLISM: LIPIDS CHYLOMICRONS
Definition Other notes
Overview:
→ smaller molecules that are produced, along with The concentration of
→ During digestion, triglycerides are hydrolyzed to glycerol, fatty acids, and cholesterol, are absorbed into cells of the plasma lipids increases
monoglycerides: intestinal mucosa (inner GI walls) for resynthesis after a meal, and returns
of the triglycerides and phosphoglycerides to normal as a result of
→ Chylomicrons are modified by the liver, a storage in fat depots and
lipoprotein that transports triacylglycerols from oxidation to provide
intestinal cells, via lymphatic system, to the energy.
bloodstream.

CLASSIFYING LIPOPROTEINS BY DENSITY

→ Phosphoglycerides are also hydrolyzed to their component substances Classification Definition
(glycerol, fatty acids, phosphate groups, and aminoalcohols) Chylomicrons carry triglycerides from the intestines to the
liver, skeletal muscle, and adipose tissue.
Very low-density newly synthesized triglycerides from the liver to
lipoproteins (VLDL) adipose tissue
Low-density lipoproteins cholesterol from the liver to cells of the body
(LDL) (“bad cholesterol”)
High-density lipoproteins collect cholesterol from the body’s tissues, and
(HDL) bring it back to the liver (“good cholesterol”)

CHOLESTEROL AND LDL

Definition Other notes
→ Cholesterol is involved in the formation of cell HDL’s are able to remove
membranes, the insulation of nerves, the cholesterol from plaques
synthesis of a number of hormones, and the in the arteries and
digestion of food transport it to the liver
→ LDL’s transport cholesterol into the wall of an for excretion or reuse
*TAGs= triaglycerols) artery causing the formation of plaques (an
accumulation and swelling in artery walls), and
leading to atherosclerosis
 BIOCHEM NOTES
GLYCOGEN AND GLUCOSE STORES FATTY ACID OXIDATION
Definition Other notes Definition Other notes
→ Carbohydrates from dietary sources and Brain cells do not obtain → Fatty acids that enter tissue cells cannot be oxidized to This reaction is
glycogen catabolism are used preferentially for nutrients from blood; produce energy until they pass through the referred to as
energy production by some tissues, such as the RBC s do not have membrane of the mitochondria activation of the
brain and active skeletal muscles mitochondria, and → the fatty acid is converted into fatty acyl CoA by fatty acid because
→ Body stores of glycogen are depleted after only a cannot do fatty acid reaction with coenzyme A, with energy provided by the fatty acyl CoA is
few hours of fasting, which requires fatty acids oxidation ATP: a high energy
stored in triglycerides to be used as energy compound.
sources.

FAT MOBILIZATION
Definition Other notes → catalyzed by acyl CoA synthetase
→ Process where the need fatty acids for energy, the In the blood,
endocrine system produces several hormones, including mobilized fatty Additional notes:
epinephrine, which interact with adipose tissue, acids form a There are three parts to the process by which fatty acids are broken down to
stimulating the hydrolysis of triglycerides to fatty acids lipoprotein with
obtain energy:
and glycerol, which enter the blood stream. the plasma
1. The fatty acid must be activated by bonding to coenzyme A
→ Fatty acids are transported to the tissue cells that need protein called
them. The glycerol is water soluble, so it dissolves in the serum albumin 2. The fatty acid must be transported into the mitochondrial matrix by a
blood and is also transported to cells that need it shuttle mechanism
3. The fatty acid must be repeatedly oxidized, cycling through a series of
GLYCEROL METABOLISM four reactions, to produce acetyl CoA, FADH2, and NADH
Definition Other notes
→ Dihydroxyacetone phosphate is one of the chemical In the blood, B-OXIDATION
intermediates in glycolysis. It is converted to pyruvate, mobilized fatty Definition Other notes
and thus contributes to cellular energy production. acids form a Repetitive series of four biochemical Each repetition of the four-
→ The glycerol hydrolyzed from triglycerides can provide lipoprotein with reactions that degrades acyl CoA to acetyl reaction sequence generates an
energy to cells. It is converted to dihydroxyacetone in the plasma CoA by removing two carbon atoms at a acetyl CoA molecule and an acyl
two steps: protein called time, with FADH2 and NADH also being CoA molecule that has two
SERUM ALBUMIN. produced fewer carbon atoms.
 BIOCHEM NOTES
B-OXIDATION PATHWAY STEPS IN GLYCOGENESIS
Steps Description
Step 1 → Hydrogen atoms are removed from the a and b carbons,
First creating a double bond between these two carbon
dehydrogenation atoms.
→ FAD is the oxidizing agent, and a FADH2 molecule is a
product.

Step 2 A molecule of water is added across the trans double bond,

Hydration producing a secondary alcohol at the b-carbon position

Step 3 → Removal of two hydrogen atoms converts the b-hydroxy

Second group to a keto group, with NAD+ serving as the
Dehydrogenation oxidizing agent.
→ The required enzyme exhibits absolute stereospecifi city
for the L isomer.
→ The b-carbon atom has been oxidized from a 9CH29
group to a ketone group

Step 4 Fatty acid carbon chain is broken between the a and b

Thiolysis carbons by reaction with a coenzyme A molecule
 BIOCHEM NOTES
ATP FROM FATTY ACIDS KETONE BODIES
→ The activation of stearic acid by coenzyme A to form stearoyl CoA comes Definition Other notes
from the hydrolysis of 2ATPs Produced from acetyl CoA when an excess of acetyl ketone bodies are
→ Acetyl CoA can enter the citric acid cycle/electron transport chain and CoA from fatty acid degradation accumulates carried by the blood to
form 10 ATPs (total = 9x10= 90 ATP) because of triacylglycerol–carbohydrate metabolic body tissue, mainly the
→ Each 𝐹𝐴𝐷𝐻2 yields 1.5 ATP (total = 8x1.5= 12 ATP), and each NADH yields imbalances brain, heart and skeletal
2.5 ATPs (total = 8x2.5 = 20) muscles, where they
→ from one 18-C stearic acid molecule, 120 molecules of ATP are formed may be oxidized to meet
energy needs.
Oxidation product ATP/Unit Total ATP
9 Acetyl CoA 10 90
Under normal
8 FADH2 1.5 12 conditions, the
8 (NADH+, H+) 2.5 20 concentration of ketone
Total ATP from 18C fatty acid 122 bodies in the blood
A. Reduction of the ketone group present in
Activation step -2 averages 0.5 mg/100mL.
acetoacetate to a secondary alcohol produces
Final ATP from 18X fatty acid 120 ATP b-hydroxybutyrate
Two of the ketone
→ Stearic acid (18 C) vs. Glucose (6) bodies are acids, and
o The complete oxidation of a single glucose molecule produces 32 their accumulation in the
ATPs blood results in a
o Since three glucose molecules have 18 Cs (3x6=18), three glucose particular acidosis (low
molecule would produce 96 ATP blood pH)
B. Decarboxylation of acetoacetate produces
o A stearic acid molecule (also 18 Cs) produces 120 ATP acetone
→ Lipids are nearly 25% more efficient than carbohydrates as energy-
storage systems.

CHANGES CAUSED BY FASTING

Concept
→ most acetyl CoA produced during
fatty acid metabolism is processed
through the citric acid cycle
→ During fasting, the balance
between carbohydrate and fatty
acid metabolism is lost, and fatty
acids become the body’s primary
source of energy.
Other notes
Oxaloacetate is also used for
gluconeogenesis to a greater extent as
the cells make their own glucose. KETONE DISEASES
 lack of oxaloacetate reduces the Diseases Definition
activity of the citric acid cycle, Ketonemia Ketones in the blood; higher than 20mg/100mL of blood
and acetyl CoA produced by fatty Ketonuria Ketones in urine; a level of about 70mg/100mL of blood
acid oxidation builds up faster Ketosis Condition when ketonemia, ketonuria, and acetone breath
than it can be processed by the exist simultaneously
citric acid cycle.
 BIOCHEM NOTES
Ketoacidosis Two of the ketone bodies are acids, and their accumulation
in the blood results in a particular acidosis (low blood pH)

KETOGENESIS (KETOSIS) PATHWAY

Steps Description
Step 1 Two acetyl CoA molecules combine to produce acetoacetyl
First CoA, a reversal of the last step of the b-oxidation pathway via
condensation a condensation reaction

Step 2 Acetoacetyl CoA reacts with a third acetyl CoA and water to
Second produce 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and
condensation CoA-SH

B VITAMIN AND METABOLIC PATHWAY

Step 3 HMG-CoA is cleaved to acetyl CoA and acetoacetate Vitamin B Metabolic pathway
Chain cleavage involved
Niacin Fatty acid to acetyl CoA
acting as NAD+, CoA,
FAD
Riboflavin Acting as FAD
Pantothenic Acting as CoA, acetyl-
Step 4 Acetoacetate is reduced to b-hydroxybutyrate. The reducing acid CoA, ACP
Hydrogenation agent is NADH biotin
*for the processes of B-oxidation,
ketogenesis, and lipogenesis.
 BIOCHEM NOTES
INTERRALATIONSHIPS BETWEEN
CARBOHYDRATE AND LIPID METABOLISM