MODULE 3.

ILLUSTRATING THE CATABOLIC REACTIONS OF

THE BIOMOLECULES AND THE EFFECT OF
VITAMINS, POISONS AND DRUGS

LO 3.7 Illustrate the catabolic reactions of the

biomolecules and the effect of vitamins,
poisons and drugs
 Digestion and absorption of Fuel Molecules
Digestion - is the process by which food molecules are broken down
into smaller soluble molecules that can be absorbed into the blood
through intestinal walls.
 involves the use of hydrolases – the hydrolytic enzymes
 most require digestion: carbohydrates, proteins and fats.
 Food nutrients which do not require digestion:
monosaccharides, inorganic salts, vitamins

Salivary digestion:
 saliva is 99.5% water and 0.5 % mucin, a glycoprotein that acts as
lubricant contains salivary amylase, catalyzes hydrolysis of starch
 lingual lipase, catalyzes the hydrolysis of triglycerides
 functions of saliva: to moisten the food, and as excretory fluid of
certain drugs, such as morphine and alcohol, and inorganic ions,
such as K+, Ca2+ HCO32- and SCN-
 optimum pH is 6.6
Gastric digestion:
Gastrin – produced in the stomach as food enters into, diffuse into the
blood which then carries it back into the stomach where it stimulates
the flow of gastric juice
Gastric Juice:
 secreted by glands in the walls of the stomach.
 clear, pale yellow liquid with a pH of 1.0 – 2.0
 97-99% water and up to 0.5% HCl (denatures protein)
 contains the zymogen pepsinogen and enzyme gastric lipase as
well as intrinsic factor secreted by the parietal cells in the walls of
the stomach which promotes the absorption of Vit B12
Intestinal Digestion:
Secretin – stimulates the pancreas to release the pancreatic juice into
the small intestine
 its released from the mucosa is stimulated as acidic material from
the stomach enters the small intestine.
3 types digestive juices (enter in the small intestine)
a. pancreatic juice
b. intestinal juice
c. bile
Pancreatic Juice- contains trypsinogen, chymotrypsin, caboxypeptidase,
pancreatic lipase, proelastase, and pancreatic amylase, In addition, it
contains also cholesterol ester hydrolase ( acts on cholesterol ester
forming free cholesterol and fatty acids), ribonuclease,
deoxyribonuclease and phospholipase A2.

Intestinal Juice – contains aminopeptidase, dipeptidase, sucrase,

maltase, and lactase and enzymes that act on phosphoglycerides,
nucleoproteins and organic phosphates.

Bile - produced in the liver and stored in the gallbladder

 released is stimulated by Cholecystokinin (CCK)
 a yellowish brown green viscous liquid with a pH of 7.8 to 8.6
 contains bile salts, bile pigments and cholesterol
 Functions: neutralize the acid entering from the stomach to the
small intestine and in the removal of many drugs and poisons in
the body as well inorganic ions as Calcium, zinc and mercury
Bile salts: include sodium glycocholate and sodium taurocholate,
derived from cholic acids, lowers surface tension and increase
surface area, thus aiding in the emulsification of fats.

Bile pigments: red blood cells lasts about 120 days and is then
destroyed, the hemoglobin is broken down to globin and heme

*If the bile duct is blocked, the bile pigment remains in the blood
stream, producing jaundice which recognizable by the yellow
pigmentation of the skin.*

Cholesterol: excess cholesterol is excreted by the liver and carried to

the small intestine in the bile. Sometime it precipitates in the
gallbladder producing gallstones
Polysaccharide hydrolysis monosaccharides

mouth: with the enzyme ptyalin (amylase) starch will by hydrolyze to

maltose. The principal function of saliva is to lubricate and
moisten the food so it can be easily swallowed
stomach: salivary amylase ceases as it becomes mixed with the acid
content of the stomach, no further hydrolysis of starchwill take
place.
intestine: major digestion of carbohydrates will take place through the
action of enzymes in the pancreatic and intestinal juices
 pancreatic amylase hydrolyzed starch and dexrtrins to
maltose
 intestinal mucosal cells contains maltase which catalyzed the
hydrolysis of maltose glucose units; sucrase which catalyzes
the hydrolysis of sucrose to glucose and fructose; and lactase
which catalyzes the hydrolysis of lactose to galactose and
glucose.
Absorption:
Glucose, fructose and galactose are directly absorb into the
blood stream by diffusion and active transport.
Fats hydrolysis fatty acids + glycerol
mouth: lingual lipase acts on trilgycerides, particularly of the type
found in milk
 pH range of activity 2.0 to 7.5 and has an optimum pH of 4.5.
It can possibly continue its activity even at the low pH of the
stomach.
stomach: gastric lipase is present but only very little digestion of fats
takes place because the pH of the stomach ( 1.0 to 2.0) is far
below the optimum pH of this enzyme (7.0 to 8.0).
intestine: pancreatic lipase catalyzes the hydrolysis of fats into fatty
acids and glycerol with the aid of the bile which emulsifies the
fats so they can be acted upon readily by pancreatic lipase.
Absorption:
Monoglycerides and diglycerides, fatty acids and glycerol pass
through the intestinal mucosa, where they are reconverted into
triglycerides and phosphoglycerides which enter in the lacteals, the
lymph vessels in the villi in the walls of small intestine. From the lacteals
these products pass into the thoracic duct ( a main lymph vessel) and
then into the blood stream.
Proteins hydrolysis amino acids
mouth: no hydrolysis of proteins
stomach: the precursor pepsinogen is converted to pepsin (catalyzes
the hydrolysis of proteins to polypetides) with the hydrochloric acid
of the stomach.
intestine: the zymogen trypsinogen from the pancreatic juice is
change to trypsin by intestinal enzyme enterokinase.
 Trypsin changes chymotrypsinogen, another pancreatic
zymogen, into chymotrypsin. Trypsin and chymotrypsin
catalyze the hydrolysis of proteins, proteases, and peptones
to polypeptides.
 Their optimum pH is 8.0 to 9.0.
 Intestinal enzymes amino petidase and dipeptidase catalyze
the hydrolysis of polypetides and dipeptides to amino acids.
Absorption:
Absorb in the blood in the form of amino acids, occasionally
proteins escape from digestion and are directly absorbed into
the blood. Ex. Antibodies of cholostral milk
Absorption of iron:
 About 5 to 10% of orally ingested iron is absorbed in the upper
duodenum region of the small intestine
 The stomach acidity along with a reducing agent (ascorbic acid)
and proteins help reduce dietary iron to stable, absorbable,
water soluble Fe2+ complex.

Factors that make the absorption of iron difficult:

a. Most iron has to be reduced from Fe3+ to Fe2+
b. The relatively high pH of the small intestine increases the
formation of insoluble iron compounds.
c. Iron forms insoluble compounds with bile salts
d. Phosphates forms insoluble iron compounds
e. iron absorption requires stomach acidity
Absorption of vitamins
are absorbed in the upper small intestine, fat soluble vitamins (A, D,
E, K) require fats and bile to be absorbed
Formation of the Feces:
 After absorption the contents of the small intestine in semi-fluid
form, pass into the large intestine, where water is reabsorbed
leaving behind the residue called the feces.
 the condition in the large intestine favors the growth of bacteria
which may comprise about ¼ to ½ of the feces and cause the
fermentation of carbohydrates to H2, CO2, and CH4,
 the amino acid tryptophan, undergo a series of reaction
producing skatole and indole which are responsible for the odor
of the feces.
Dietary Fibers – denotes substances that cannot be digested, include:
cellulose, lignin, pectins, gums and pentosans.
 aiding water retention during passage of food through the
gastrointestinal system, thereby producing feces that are softer
and larger. (insoluble fibers are beneficial to colon function and
more soluble fibers in lowering serum cholesterol)
 The Absorptive State

https://www.slideshare.net/syedahussaini7355/chapter-7-metabolism-and-energy
 THE METABOLISM OF CARBOHYDRATES

Digestion and Absorption of Carbohydrates

Polysaccharides hydrolysis glucose
Sucrose hydrolysis glucose + fructose
Lactose hydrolysis glucose + galactose
Blood Sugar Level:
 Normal blood sugar level remains constant at about 80 mg/100mL
of blood, but with a range of 70mg to 100mg/100ml of blood.
 glucose in the blood stream may be transported to the tissues, or
it may be converted into glycogen to be stored in the liver.
 The liver is the key organ for regulating the concentration of
glucose in the blood.
 This activity is governed by several hormones
(a) Insulin (pancreas,) accelerates oxidation of glucose in the cells,
increases glycogenesis, decreases glycogenolysis, and promotes the
formation of fat from glucose – thus removes glucose from the
blood stream;
(b) Epinephrine (adrenal medulla) changes liver glycogen to glucose and
muscle glycogen to lactic acid, secreted into the bloodstream during
periods of emotional stress:
(c) Glucagon (pancreas) has an effect opposite to that of insulin – thus
raises blood sugar level.
(d) Somasotropic hormone (STH) (growth hormone -GH) antagonizes
insulin by unknown mechanism, raises serum glucose, a feature in
acromegaly of which hyperglycemia is caused by an STH-producing
pituitary tumor.
(e)Somatomedins (proinsulin, effects resemble that of insulin, promote
glucose and amino acid uptake by cells, stimulate the synthesis of
glycogen, protein and triglycerides.
(f)Thyroid hormone – by unknown mechanism have some effect on
glucose levels.
(g) Glucocorticoids inhibit glycolysis and stimulate gluconeogenesis
providing more pyruvate and OAA as fuel to gluconeonenesis. It
stimulate the liver to produce the glucoeneogenetic enzymes such as
glucose-6-phosphatase, pyruvate carboxylase and PEP carboxylase.
Hypoglycemia – is a condition resulting from a lower than normal blood
sugar level.
Hyperglycemia – is a condition resulting from a higher than normal
blood sugar level.
Processes Counteracting Hyperglycemia
1. The liver may remove glucose from the blood stream, converting
it into glycogen for storage.
2. The muscles will also take glucose from the circulation to convert
to muscle glycogen.
3. Muscle will take glucose from the circulation to oxidize it to
produce energy.
4. Glucose may be converted into fat and stored in the fat depot.
Glucose Tolerance Test – measures the ability of tissues to absorb
glucose from the blood. One part of the test depends on the fact that
kidneys have only limited ability to reabsorbed glucose as they filter
and purify the blood.
Glycosuria – is a condition in which glucose appears in the urine and
the blood glucose level at which this occurs is called renal
threshold.
Glycogen – serves as a reservoir for maintenance of the blood sugar
level.

THE FLOW OF CARBON ATOMS IN THE MAJOR METABOLIC PATHWAYS OF

GLUCOSE METABOLISM
THE FLOW OF CARBON ATOMS OF GLUCOSE METABOLISM WITH THE KEY
ENZYMES
GLUCOSE METABOLIC PATHWAYS

Glycogenesis – conversion of glucose to glycogen, stimulated by the

pancreatic hormone, insulin.
 couple with the influx of K+ into the cell.
 glycogen stored in the liver can supply the body for 12 to 24
hours.

*Hyperkalemia – ( a high serum potassium level) – is usually treated

initially by giving glucose and insulin to induce glycogenesis and the
concomitant of K+ from the serum.

*Type IV glycogen storage disease – the hereditary absence of

branching enzyme (a-1,4-glucan branching enzyme) leads to the
accumulation of long glucose polymers with few branches.
Glycogenolysis – hydrolysis of glycogen to glucose, stimulated by the
pancreatic hormone, glucagon ( in the liver but not in the skeletal
muscle) and epinephrine.
 the first step is the phosphorylation of it’s a-1,4-glycosidic
bond by glycogen phosphorylase.
 Cylic AMP – mediated the activation of glycogen phosphorylase
and inhibition of glycogen synthase
Active protein kinase phosphorylates two enzymes:
a. phosphorylase kinase – becomes active
b. glycogen synthase – becomes inactive
effect: turning on glycogen breakdown and glycogen synthesis off.
Protein phosphatase 1 removes phosphate from (a) phosphorylase
kinase (b) phosphorylase and (c) glycogen synthase b
effect: slow down glycogen breakdown and favors glycogen synthesis
Cyclic –AMP PHOSPHODIESTERASE – inactivates cyclic- AMP

DISORDERS ASSOCIATED TO GLYCOGENOLYSIS

TYPE V GLYCOGEN STORAGE DISEASE (Mc Ardles disease)
 cause by hereditary absence of muscle glycogen phosphorylase.
 lead to accumulation of glycogen in the muscles
 causing muscle cramps and limited exercise tolerance.
TYPE III GLYCOGEN STORAGE DISEASE
 cause by the deficiency of amylo-1,6-glucosidase or oligo-1,4
1,4-glucan transferase
 accumulation dextrin in the tissue
GLUCOSE CATABOLISM

I. Degradation to CO2, H2O and energy:

A. Glycolysis – glucose is oxidized to two molecules of pyruvate

Glucose + 2NAD+ + 2HPO42- + 2 ADP glycolysis 2NADH + 2ATP +
2 Pyruvate
B. Oxidation and Decarboxylation of Pyruvate
Pyruvate + CoASH + NAD+ AcetylCoA + CO2 + NADH + H+

C. The Tricarboxylic Acid Cycle – acetyl CoA is oxidized to two

molecules of CO2
AcetylCoA + 3NAD+ + FAD +HPO42- + ADP CoASH + ATP +
FADH2 +3NADH + 3H+ + 2CO2
(A, B, and C are anaerobic (oxidation in the absence of O2) but rather
there is a build up of reduced coenzymes.)
GLUCOSE CATABOLISM

I. Degradation to CO2, H2O and energy:

D. Oxidative Phosphorylation (Electron transport system) M

- generate the major share of ATP produced during glucose
catabolism
NADH + 3ADP + 1/2 O2 + Pi + H+ NAD+ + 3ATP + H2O

FADH2 + 2ADP + 1/2 O2 + 2Pi + H+ FAD + 2ATP + H2O

*Within the mitochondria, the site of respiration, electrons are not

passed directly from reduced coenzymes to molecular oxygen. Rather,
they are passed from one electron acceptor to another and then to
molecular oxygen.
GLUCOSE CATABOLISM
II. Reduction to lactate: lactate fermentation
pyruvate + NADH + H+ lactic acid + NAD+
 during strenuous muscle activity or other conditions when the supply
of oxygen is not adequate for reoxidation of NADH, cells turn to the
reduction of pyruvate to lactate as a means of regenerating NAD+.
 when the blood lactate reaches a concentration of about
0.4g/100mL, muscle tissue becomes almost completely exhausted.
 lactic acid is metabolic dead end. For its utilization as energy it must
be converted back to pyruvic acid that requires the enzyme, lactate
dehydrogenase. Deficiency
of this enzyme allows lactic acid
to accumulate leading to
lactacidosis, which, if untreated,
can be fatal.
Cori Cycle –

https://www.slideshare.net/SumiaWaleed/cori-cycle-95609166
GLUCOSE CATABOLISM

III. Converted to Pentoses: Pentose Phosphate Pathway

 alternative pathway for the oxidation of glucose to CO2 and H2O
glucose-6-phosphate + 2NADP ribose-6-phosphate + 2NADPH
+CO2
important characteristics:
a. provide a pool of pentoses for the synthesis of nucleic acids
b. it uses up NADP as an oxidizing agent and generate reduced
coenzyme NADPH, reducing agent in the biosynthesis of other
biomolecules ( ex. Fatty acid),
c. maintain proper levels of the antioxidase glutathione in red blood
cells (without such red blood cells are easily oxidized by a variety of
drugs).

REGULATION: controlled by regulation of the first enzyme in the

pathway, glucose-6-phosphate dehydrogenase.
CONDITION ASSOCIATED: Hemolytic anemia – resulting from glucose-6-
phosphate dehydrogenase deficiency.
GLUCOSE CATABOLISM

IV. Reduction to Ethanol: Alcoholic fermentation

Pyruvate + NADH + H+ Acetaldehyde +NAD +
Acetaldehyde +NADH + H+ ethyl alcohol + NAD+

 Yeast and several other organisms have developed an alternative

pathway for the regeneration of NAD+ under anaerobic condition

 alcoholic fermentation – metabolic pathway that converts glucose

to ethanol and carbon dioxide.

 catalyzed by pyruvate decarboxylase and alcohol dehydrogenase

 Overview of Cellular respiration

https://www.quora.com/What-are-the-
https://www.slideshare.net/drjayeshpatidar/metabolism-36941624
products-of-cellular-respiration
 DEGRADATION OF GLUCOSE TO CO2, H2O & ENERGY
I. GLYCOLYSIS

https://microbiologyinfo.com/glycolysis-10-steps-
explained-steps-by-steps-with-diagram/
I. GLYCOLYSIS
IMPORTANT FEATURES OF GLYCOLYSIS
• Two ATP consuming steps
1) glucose to glucose-6-phosphate
2) fructose-6-phosphate to fructose-1,6-diphosphate
• Two oxidation-reduction reactions
(2) glyceraldehyde-3-phosphate to (2) 1,3- diphosphoglycerate
• Three irreversible steps: those catalyzed by
1) hexokinase
2) phosphofructokinase
3) pyruvate kinase
• Occurrence: CYTOSOL
• Energetics
1) consumed 2 moles of ATP
2) produced 4 moles of ATP
3) produced 2 moles of NADH
I. GLYCOLYSIS: NAD+/NADH SHUNTS TO THE MITOCHONDRIA
a. glycerol-phosphate shuttle

Prominent in the muscle, which enables it to sustain a very

high rate of oxidative phosphorylation
http://themedicalbiochemistrypage.org/glycolysis-and-the-regulation-of-blood-glucose/
I. GLYCOLYSIS: NAD+/NADH SHUNTS TO THE MITOCHONDRIA
b. malate-aspartate shuttle

Common in the liver and in the heart muscles

I. GLYCOLYSIS
• DISORDERS ASSOCIATED TO IRREGULARITIES IN THE GLYCOYTIC
PATHWAY
1. Hemolytic Anemia – lacking one of the glycolytic enzyme.
2. Lactic Acidosis – resulting from the scarcity of NAD+ when
glycolysis exceeds oxidative metabolism whereby lactate
produced so rapidly that the liver cannot remove it fast
enough.
lactic acid increase, and metabolic acidosis ensues
• REGULATION OF GLYCOLYSIS
hexokinase: inhibited by glucose-6-phosphate
phosphofructokinase: inhibited by high ATP and citrate
concentration and is activated by high concentration of ADP
and AMP
the conversion fructose-1,6-diphosphate commits the
C-skeleton of glucose irreversibly to glycolysis.
METABOLISM OF GLYCERALDHYDE
a. may be phosphorylated to glyceraldehyde-3- phosphate
b. may be reduced to glycerol and then phosphorylated to
glycerophosphate, a metabolic intermediate required
for the synthesis of phospholipids
ENTRY OF FRUCTOSE AND GALACTOSE INTO GLYCOLYSIS
II. OXIDATION AND DECARBOXYLATION OF PYRUVATE TO
ACETYL COENZYME A
 pyruvate dehydrogenase (PDH) reaction
 under aerobic conditions, pyruvate is converted to acetylCoA and
becomes a fuel for the tricarboxylic acid cycle (KREB’S CYCLE).
pyruvate + CoASH + NAD+ acetylCoA + CO2 + NADH + H+

REGULATION:
A. There are two enzymes regulates PDH reaction
1. PDH KINASE: stimulated by high ratios of ATP/ADP, NADH/NAD +
or acetylCoA/CoA
 phosphorylates the active form of PDH, making it inactive
2. PDH phosphatase: stimulated by insulin and Ca2+, removes
PO43- from inactive PDH thereby reactivating it.
B. Acetyl CoA and NADH: inhibit PDH while AMP stimulates the
enzyme complex
III. OXIDATION OF ACETYLCoA TO CO2: THE CITRIC ACID OR
TRICARBOXYLIC ACID CYCLE (KREB’S CYCLE)
III. OXIDATION OF ACETYLCoA TO CO2: THE CITRIC ACID OR
TRICARBOXYLIC ACID CYCLE (KREB’S CYCLE)

• THE OVERALL CHEMICAL EQUATION: TCA

ACETYCoA + 3NAD+ +FAD +HPO42- + ADP CoASH + ATP + FADH2 + 3NADH + 3H+ + 2CO2

• Regulation on the Citric Acid Cycle

 Citrate synthase ( step 1) inhibited by ATP
 Isocitrate dehydrogenase (step 3) and/or NADH + H+
 -ketoglutarate dehydrogenase thus shuts off the cycle
(step 4)
 isocitrate dehydrogenase (step 3): stimulated by ADP & NAD+
 high concentration of aceytl CoA: speeds up the cycle
 α-ketoglutarate dehydrogenase: inhibited by its end product
succinyCoA andNADH
 overall cycle: inhibited by high ATP
III. OXIDATION OF ACETYLCoA TO CO2: THE CITRIC ACID OR
TRICARBOXYLIC ACID CYCLE (KREB’S CYCLE)

• IMPORTANT FEATURES
a. α-ketoglutarate & OAA: often remove from the cycle to serve as
precursor for glutamate and aspartate respectively
b. FAD: used as coenzyme for an oxidation-reduction
reaction that generate C=C.
c. NAD+: used as coenzyme for an oxidation-
reduction reaction that generate C=O.

• ADVANTAGES OF THE CYCLIC NATURE OF THE

DEGRADATION OF ACETATE ION IN THE TCA
1. maximized energy production
2. citric acid cycle components also provide raw materials for
amino acid synthesis as the need arises.
3. the many component cycle provides an excellent method for
regulating the speed of catabolic reactions.
III. OXIDATION OF ACETYLCoA TO CO2: THE CITRIC ACID OR
TRICARBOXYLIC ACID CYCLE (KREB’S CYCLE)

• The role of B Vitamins in the Kreb’s Cycle

a. Riboflavin – is in the form of flavin adenine dinucleotide (FAD),
a cofactor in the -ketoglutarate dehydrogenase complex and
also succinate dehydrogenase.
b. Thiamine, vitamin B1 – is the coenzyme for the decarboxylation
in the -ketoglutarate dehydrogenase reaction; lipoic acid also
is involved in the decarboxylation of -keto acids
c. Niacin – is in the form of nicotinamide adenine dinuleotide
(NAD+), the coenzyme for the dehydrogenases in the citric acid
cycle.
d. Panthothenic acid - is a part of the CoA.
IV. OXIDATIVE PHOSPHORYLATION OR THE ELECTRON
TRANSPORT SYSTEM
IV. THE ELECTRON TRANSPORT SYSTEM & OXIDATIVE
PHOSPHORYLATION
The chemiosmotic theory (proposed by Peter Mitchell in England
– l961) – the Principles
1. The mitochondrial membrane is impermeable to ions,
particularly to H+, which accumulates outside the inner
membrane, causing an electrochemical potential difference
across the inner membrane.
2. The synthesis of ATP occurs under the influence of an enzyme
on the inside of the inner mitochondrial membrane.
3. ATP synthesis occurs because of the movement of protons
through special ports in the membrane (not through the
membrane itself) from the outside to the inside of the inner
mitochondrial membrane.
4. The potential difference drives membrane-located ATP
synthase
5. The respiratory chain is folded into three oxidation-reduction
loops in the membrane, each loop corresponding to a part of
the respiratory chain.
IV. OXIDATIVE PHOSPHORYLATION OR THE ELECTRON
TRANSPORT SYSTEM

Poisons that inhibits the respiratory chain

1. Poisons that inhibit the formation of coenzyme Q-

includes barbiturates (amobarbital), antibiotics
(piercidin A) and insecticides (rotenone)

2. Poisons that inhibit the conversion of cytochrome b to

cytochrome c – includes H2 S, CO and cyanide
(HCN)

3. Poisons that act as “uncouplers” to oxidative

phosphorylation – includes 2,4-dinitrophenol,
dinitrocresol, m-chlorocarbonyl cyanide
phenylhydrazone, and snake venoms.
 CATABOLISM OF FATTY ACIDS
I. First Phase of Fatty Acid Catabolism - Hydrolysis of Triglycerides

TRIGLYCERIDES + H2O GLYCEROL + FATTY ACIDS

 Fatty acids are transported with albumin

 Release of fatty acids from the adipose tissue into the blood
stream is stimulated by several hormones, including
epinephrine, adrinocorticotropic hormone, growth hormone
and thyroxine.

 Fatty acid accumulation in adipose tissue and storage as

triglycerides is stimulated by high levels of glucose and insulin
in the blood stream.
II. Second Phase of Fatty Acid Catabolism – Oxidation of Fatty Acids

3 major stages:
a. Activation of free fatty acids
- free fatty acid in the cytoplasm is converted to a thioester
formed with coenzyme A, coupled with the hydrolysis of ATP to AMP
and pyrophosphate. Within the cytoplasm, pyrophosphate is further
hydrolyzed to two HPO42-.
ATP AMP
fatty acid + CoASH fatty acyl CoA

thiokinase
ATP + H2O AMP + PPi

PPi + H2O 2 Pi

* because activation of fatty acids is coupled with the hydrolysis of two

high energy phosphate anhydride bonds, the initial investment by a
cell in fatty acid oxidation is equivalent to two moles of ATP for each
mole of fatty acid oxidized.
b. Transport of Fatty Acids into mitochondria
FATTY ACYLCoA + CARNITINE FATTY ACYL-CARNITINE + CoASH
In the cytoplasm fatty acyl CoA and carnitine undergo a reaction
in which the fatty acyl group is transferred from sulfur atom of
coenzyme A to oxygen atom of the secondary alcohol of carnitine.
The fatty acyl carnitine is transported through the inner
mitochondrial membrane and there the reaction is reversed. The
freed carnitine is then returned to the cytoplasm to repeat the
cycle.

https://www.barnardhealth.us/glucose-phosphate/ch2oh-hgr.html
c. β-oxidation

1. oxidation – carbon chain

is oxidized by removing
hydrogen atoms
 coenzyme: FAD
2. Hydration – water is
added to the carbon-
carbon double bond
 enzyme: Enoyl-CoA
hydratase
3. Oxidation – the
secondary alcohol is
oxidized to ketone.
 enzyme:
Hydroxyacyldehydroge
nase
 coenzyme: NAD+
4. Cleavage of acetyl CoA –
through addition of CoA-
SH
 enzyme: Thiolase- -
ketothiolase
https://biochemistryquestions.wordpress.com/2008/11/01/how-to-calculate-the-energetic-balance-of-the-
total-oxidation-of-a-fatty-acid-2/
Oxidation of Propanoate
 Fatty acids with even number of carbon atoms are degraded
completely to acetyl CoA. While they are not nearly as common,
fatty acids with odd numbers of carbon atoms do occur in nature.
The final  – oxidation of an odd-numbered carbon chain gives
the thioester of propanoic acid.

Propanoyl Co A is converted to succinyl CoA

Steps:
a. Carboxylation
b. methylmalonyl CoA is isomerize to succinyl CoA
*Pernicious Anemia (great reduction of red blood cells, increase in size
with no hemoglobin) – is a disease caused by a deficiency of vitamin
B12 or due to a deficiency of a substance called intrinsic factor that is
necessary for the absorption of B12 through the walls of
gastrointestinal tract and into the blood stream. Sources of B12:
animal derived food ( kidney, liver, salmon, oysters, milk products and
eggs.
Formation of Ketone Bodies:

 Acetoacetate, - hydroxybutyrate and acetone are classed as

ketone bodies. Under normal conditions, their concentration
in plasma (the noncellular portion of the blood) is low.

a. 2 acetyl CoA is converted to acetoacetate

b. acetoacetate is reduced to secondary alcohol

c. acetoacetate loses carbon dioxide to give acetone

Ketoacidosis – acidosis that results from the accumulation of

ketone bodies. Several abnormal conditions, including
starvation, unusual diets and diabetes mellitus, lead to
increased production of ketone bodies, ketoacidosis and
spilling of ketone bodies into the urine (ketonuria)
KETONE BODIES

https://slideplayer.com/sli
de/6899180/
 Role of the Liver in Lipid Metabolism

https://www.slideshare.net/drjayeshpatidar/metabolism-36941624
CATABOLISM OF PROTEINS:
 digestion: hydrolyzed proteins to amino acids
 absorption: through the villi of the small intestines in the form of
amino acids and enter the amino acid pool of the body
Nitrogen Balance (the body excretes as much nitrogen per day as is
taken in with food)
 amino acids in the body can be either used to synthesize new
tissues, the replacement of old tissues and the formation of various
substances required in the body such as hormones and enzymes, or
they are converted to fat or oxidized to furnish energy.
 protein in the body is constantly degraded and then resynthesized.
Protein turnover rate– the time required to degrade a protein and then
resynthesized ; ranges from few minutes for proteins such as
hormones and enzymes or 3 years for structural proteins such as
collagen.
Degradation rate is expressed in terms of half life (t1/2) ; the time
required for its concentration to reduced to 50% of its original
value.Ex. tryptophan oxygenase and tyrosine transaminase – T1/2 is
about 2 hours

Positive nitrogen balance – the body excretes less nitrogen than it

acquires from food.
Ex. Growing children and person recovering from wasting illness

Negative nitrogen balance - the body excretes more nitrogen than it

acquires from food.
Ex. Starvation, malnutrition, prolonged fever and various wasting
illnesses.

Kwashiorkor – a protein deficiency disease characterized by wasting

away of fat and muscle and a degeneration of many of the internal
organs.
CATABOLISM OF AMINO ACIDS:
Amino acids that the body does not need for tissue building or that
are not the correct type for a certain purpose are broken down
to ammonia, carbon dioxide and water.

Deamination (also called oxidative deamination)

 is a catabolism reaction whereby the -amino group of an amino
acid is removed forming an -ketoacid and ammonia.
 occurs primarily in the liver and the kidneys
 enzyme: amino acid oxidase
Formation of urea:
Ammonia is a toxic by-product of the deamination of amino acids
and must be removed from the body, predominantly in the form
of compound, urea (the only one principal way to dispose off
excess nitrogen). The pathway for the conversion of ammonia to
urea is called the urea cycle. Three amino acids are involved in
the conversion of ammonia to urea- arginine ornithine and
citrulline

Overall reaction:

The blood picks up the urea (the end product of protein

metabolism) from the liver and carries it to the kidneys, where it is
excreted in the urine.
https://www.ncbi.nlm.nih.gov/Omim
/Images/ureacycle.html
METABOLIC DISORDERS ASSOCIATED WITH THE UREA CYCLE
Hyperammonemia – caused by a lack of the enzyme carbomyl
phosphate synthetase. One of the effects is mental retardation.

Citrullinemia – caused by the absence of or decreases levels of the

enzyme arginine succinate synthase

Arginosuccinase aciduria – caused by a lack of the enzyme

arginosuccinase or arginosuccinate lyase;

Fatal to children at about age 2.

THE FATE OF -KETOACID:

1. It can be catabolized to carbon dioxide, water and energy in the citric

acid cycle.
Ketogenic – those that can be converted to acetyl CoA and
acetoacetyl CoA
- ile, leu, trp (acetyl CoA)
- lys, phe, tyr, leu, trp (acetoacetyl)
Glucogenic – those that can be converted to pyruvate or Kreb’s Cycle
intermediate
- ala, cys, gly, ser, thr (pyruvate)
- asn, asp (oxaloacetate)
- phe, tyr (fumarate)
- ile, met, val (succinyl CoA)
- glu, arg, gln, his, pro (∂ - ketoglutarate)
2.It can be converted to carbohydrate (glycogen) or to fat
3. It can be reconverted to a different amino acid
The Interconnection Between Tissues and Metabolistic Reactions

https://www.quora.com/What-is-a-glucose-alanine-shuttle-and-its-significance-in-the-body
Decarboxylation
removal of –COOH group
produces primary amine and carbon dioxide
enzyme needed: amino acid decarboxylase and pyridoxal
phosphate as coenzyme.

general equation:

example:
histidine  histamine (plays an important role in
allergic reaction)
lysine  cadaverine
ornithine  putrescine
tyrosine  tyramine
CATABOLISM OF HEMOGLOBIN
hemoglobin - composed of iron, porphyrin ring and globin):
 life span of the red blood cell – about 120 days; ruptures at the
reticuloendothelial cells of the liver, spleen, and bone marrow.
 the globin unit metabolized as any other protein
 the body synthesizes hemoglobin at the same rate as it is
metabolized.
 iron: reused
 heme (porphyrin):
metabolized and
excreted as waste
https://www.slideshare.net/UDDent/heme-metabolism-dental2012
DISORDERS ASSOCIATED TO THE METABOLISM OF THE HEME

Hemolytic jaundice – occurs when hemolysis takes place at a very

high rate so that bilirubin accumulates in the blood.
Obstructive jaundice – occurs when the bile duct is obstructed so
that bile cannot enter into the small intestinal tract, bilirubin
accumulates in the blood.

https://www.rnpedia.com/nursing-notes/medical-surgical-nursing-notes/jaundice-nursing-management/
CATABOLISM OF NUCLEOPROTEINS:
 ribose and deoxyribose enter the normal carbohydrate
metabolic pathway
 the purines are converted to uric acid (eliminated in the urine)
 the pyrimidine are eliminated in the urine in the form of urea
*GOUT - a disorder characterized by an increased uric acid
concentration in the blood. The uric acid may deposited in
the joints, cartilages, gall
bladder (as gallstones),
and kidney (kidney stones)

https://worldhealth.net/news/go
ut-possibly-only-curable-form-
arthritis/
 Degradation of nucleic acid
Nucleoprotein

In stomach Gastric acid and

pepsin

Nucleic acid Protein

In small intestine Endonucleases: RNase and

DNase
Nucleotide

Nucleotidase

Phosphate Nucleoside

Nucleosidase

Base Ribose
https://slideplayer.com/slide/6625356/
 Significances of nucleotides
1. Precursors for DNA and RNA synthesis
2. Essential carriers of chemical energy, especially
ATP
3. Components of the cofactors NAD+, FAD, and
coenzyme A
4. Formation of activated intermediates such as
UDP-glucose and CDP-diacylglycerol.
5. cAMP and cGMP, are also cellular second
messengers.
https://en.wikipedia.org/wiki/Nucleic_acid_metabolism
 https://slideplayer.com/slide/6625356/
NH2 O
Adenosine
C C
N Deaminase N
N C HN C
CH CH
HC C HC C O
N N N
N
C N
Ribose-P Ribose-P
HN C
IMP CH
AMP
HC C
N N
Xanthine Oxidase H
Hypoxanthine
O O
C N C N
HN C HN C
C O CH
C C C C
O N N O N N
H H H H
GMP
Uric Acid Xanthine

(2,6,8-trioxypurine) The end product of purine metabolism