Table Of ContentBy
Prof. Dr. Hoda Mohammed El· Kholy
Biochemistry Department
Faculty of Medicine (For Girls),
AI Azhar University -Cairo
2018-2019
[
Review of Medical Biochemistry with
Clinical Correlations
By
Prof. Dr. Hoda Mohammed El-Kholy
Biochemistry Department
Faculty of Medicine (for Girls), AI Azhar University
Cairo
Index
Subject Page
Basic concept of metabolism ---------------------
Electron transport chain --------------------
Hormones ----------------- 10
Carbohydrate chemistry and metabolism------------------ 21
Protein chemistry and metabolism ------------------- 75
Neurotransmitters ----------------------- 124
Hemoproteins ------------------------- 126
Immunoglobulin ------------------- 145
Lipid chemistry and metabolism ----------------- 148
Metabolicintegrations -------------------- 206
Vitamins --------------- 213
Free radicals and antioxidants------------- 233
Enzymes 240
Nucleic acids chemistry 251
Nucleotide metabolism 285
Minerals and electrolytes 288
Extracellular matrix 302
Body fiuids 304
Biochemistry of cancer 315
Acids and bases 319
Preface and Acknowledgment
This book has been done for dinical students. The main subjects that have been explained were
chemistry and metabolism of carbohydrates, lipids,· proteins, _heme, nucleotides, and nucleic
acids. Metabolic integrations, body fluids, metabolism of nervous system, vitamins, enzymes,
minerals, biochemistry of cancer, and bioenergetics have been explained in brief.
I will greatly appreciate receiving from teachers and students their comments, notice of errors
and advices.
I wish to express my deep appreciation to all staff ~~mbers of biochemistry deparbnent Faculty
of Medicine, AI-Azhar UniversitY (For Girls} for their comments and good help.
Many thanks to my family who has pro~ided the assistance that have made the completion of
this work possible.
Hoda Mohammed Elkholy
Email: [email protected]
dr-hoda-elkholy@ hotmail
3
Basic Concept of Metabolism
Metabolic Pathways:
• Metabolic pathways are series of enzymatic reactions occurring in consecutive steps,
the product of one enzyme reaction becomes the substrate for the next reaction in the
sequence. The successive products of the reaction are known as metabolites or
metabolic intermediates.
• Metabolism is the sum of chemical activities in an organism
• Metabolic pathways occur in the cytoplasm, mitochondrial membrane and matrix,
lysosomes and peroxisomes.
Metabolism is divided into:
1. Anabolism (anabolic reactions).
2. Catabolism (catabolic reactions)
1. Anabolic reactions or anabolism: are processes that build complex molecules from simpler
one. Theses reactions usually consume energy usually derived from ATP (They are called
endergonic reactions).
Anabolic reactions
I
Glucose l+l Glucose II Glycerol I+ I fatty acid I Amino arid I+ I Amino acid
y~ y~
y~
I
Glycogen I Triglyceride I [YfPmin I
..;;
ATP ADP+P
Simple compounds \ j. Complex compounds
( C02, monosaccharides, amino acids, ---~......;:a,-L.:;..._......::.,~
(Polysaccharides, protein, lipids)
fatty acids ) Energy required is provided by ATP
hydrolysis
2. Catabolic reactions or catabolism: are processes that break down complex molecules into
simpler ones. These reactions usually release energy in the form of ATP or exothermic in the
surrounding environment. They!re called exergonic reactions.
Catabolism occurs in three stages:
1. Stage I (hydrolysis of complex molecules: Polysaccharide are degraded to
monosaccharides, proteins are degraded to amino acids and triacylglycerol to glycerol and fatty
acids.
2. Stage II: These smaller molecules are further degraded to acetyl CaA. In this stage, some
free energy is trapped as ATP.
4
3. Stage Ill: Is the final common pathway by which these molecules are oxidized to C02 and
water and trap the available free energy as ATP. It consists of:
a. The citric acid cycle.
b. The electron transport chain.
Catabolism
StageD
Breakdown of
complex molecules
to their component
building blocks Amino acids Single sugars Fatty acids,
glycerol
\._ ATP
D
Stage
Conversion of building
blocks to acetyi-CoA
(or other simple
intermediates)
E)
Stage
Metabolism of
acetyi-CoA to C0
2 Citric acid
and formation of ATP
cycle
(and Electron
transport chain)
5
Electron Transport Chain (ETC)
(Respiratory Chain)
Glucose and lipids are energy-rich molecules. They are metabolized by a series of oxidation
reactions usually yielding C02 and water. During oxidation of these compounds metabolic
intermediates are produced. These intermediates carry electrons and donate these electrons to
specific coenzymes-nicotinamide adenine dinucleotide (NAD•) and flavin adenine dinucleotide
(FAD) to form the energy-rich reduced coenzymes, NADH+H and FADH2. These reduced
coenzymes can, in tum, each donate a pair of electrons to a specialized set of electron carriers,
collectively called the electron transport chain. As electrons are passed down the electron
transport chain, they lose much of their free energy. Part of this energy can be captured and
stored by the production of ATP from ADP and inorganic phosphate (Pi). The remainder of the
2
free energy not trapped as ATP is used to drive other reactions such as Ca • tr~nsport into
mitochondria, and to generate heat.
Definition of electron transport chain: Electron transport chain is system of electron carriers,
which catalyze the transfer of electrons (also called reducing equivalent) derived from different
fuels in the body (in the form of reduced coenzymes as NADH+W and FADH2) to molecular
oxygen to form H20.
• It is called respiratory because the end acceptor of electrons and protons is oxygen.
Site of electron transport chain: In the inner mitochondrial membrane.
INNER' UEMBRANE
1~10
CEll. smmoaslll $a<nlldAI lIa -rge
mole='-
I
MATRIX I
• TCA CWde en:rymes
• ~.ad Gdd.a1Jon anzymac
• nttDNA.. .eRHA
• 'n \liS ribosomes
Importances of electron transport chain are:
1. It is a final common pathway for oxidation of food stuffs with release of energy.
2. Allow the energy to be released gradually in several steps because if the energy is produced
& released at one step, it will lead to loosing of most of this energy in the form of heat that can
damage the cell. Great part of the energy is stored in the form of ATP.
3. NADH+H+ and FADH produced during metabolic reactions are re-oxidized again in the
2
respiratory chain and reused again.
6
I
Food
:I wy m
Fat-~1~ Felly acids
..;.~~----~----------·:
~
I
Carbohydr.Jlo- i --.GJuCOSil,tlC %A ailyt-CoA aoo 2H t~~~·?·)·. : ~\..;·" Hj)
.N:S: (::,:_,:_;:.:::: ':~~
~=c l cyd9 •I
Protein-~~ I! RespiraDry cham
Amixl acids I
1 l.litochondrion 1 ADP
I I
~SOUTa!Sd
md!cilg ~oots
Role of the respiratory chain of mitochondria In the conversion of food energy to AlP.
Organization of respiratory chain: It is formed of:
1. Five complexes:
• Four of them (1, II, Ill, IV) can accepts or donates electrons to relatively mobile electron
carriers, until reach oxygen ~H20.
• The fifth complex is responsible for synthesis of ATP.
2. Two mobile carriers: They include coenzyme Q and cytochrome c (cyt c) which are
responsible for transport of electrons between complexes. Each carrier can receive electrons
from an electron donor, and can subsequently donate electrons to the next carrier in the chain.
• All members of the chain are proteins except coenzyme Q ( coQ).
,,,~_._• .-pltl_
C<NNAn-DH1 c~.I.-Vc
dehy.sroe-.,...
c -
Oxidative phosphorylation:
Definition: It is the coupling of oxidation in respiratory chain with phosphorylation (ATP
production) i.e. ADP is phosphorylated by inorganic phosphate (Pi) to form ATP in respiratory
·chain.
• Electrons that enter the chain via NADH+H+ support the synthesis of approximately 2.5
moles of ATP.
(Reduced NAD enters the respiratory chain at the complex 1).
• Electrons that enter the chain via FADH support the synthesis of approximately 1.5
2
moles of AT P.
(Reduced FAD enters the respiratory chain at complex II).
7
Inhibitors of ETC: Compounds (such as drugs and toxins) that prevent the passage of
electrons and protons via the respiratory chain by binding to a component of the chain, blocking
the oxidationireduction and phosphorylation reactions. Examples of inhibitors:
1. Barbiturates (such as amytal) inhibit electron transport via complex I by blocking the
transfer from Fe-S to Q.
2. Malonate is a competitive inhibitor of Succinate dehydrogenase {Complex II).
3. Antimycin A, dimercaprol and BAL inhibit the respiratory chain at complex Ill.
4. The classic poisons HS, carbon monoxide, and cyanide inhibit complex IV and can
2
therefore totally arrest respiration.
5. Oligomycin: it is the antibiotic which completely blocks oxidation and phosphorylation by
blocking the flow of protons through ATP synthase.
Blocking electron transfer by
any one of these inhibitors
stops electron flow from substrate
to oxygen because the reactions of
the electran transport chain are
tightly coupled like meshed gears.
Uncoupling of oxidation with phosphorviation:
The processes of oxidation and phosphorylation are tightly coupled. If these two processes
are uncoupled, the process of oxidation will proceed without phosphorylation (no ATP
production), and thus the energy of the reaction will be lost in the fonn of heat and gives the
sensation of hotness.
Uncouplers:
Definition: Substances that allow oxidation to proceed but prevent phosphorylation.
(uncoupling oxidation with phosphorylation). Energy is released in the form of heat with
sensation of hotness when individual uses this uncouplers.
• Uncouplers decrease the pH and electrical gradient thus increase the permeability of
the inner mitochondrial membrane to protons, thus allow protons to re-enter the
mitochondrial matrix without passing through the complex V and the energy is not
captured as ATP but released as heat
Uncouplers include:
1.Physioloaical uncouplers:
1. Thermogenine: Is a physiological uncoupler found in brown adipose tissue that functions
to generate body heat, particularly for the newborn and in animals. It acts as H+ carrier
allowing transport of H+ to the inside of the mitochondria without passing through complex
V, so no ATP is produced, and the energy is released in the form of heat
2. Thyroxin at high doses as in case of thyrotoxicosis. It causes mitochondrial swelling.
3. Bilirubin at high doses as in case of hyperbilirubinemia.
8
II. Synthetic:
1. Some hydrophobic weak acids as 2, 4 dinitrophenol (2 ,4 DNP) which is used for weigh loss.
Uncoupling proteins create a
"proton leak,• allowing protons
to reenter the mftoc:hondrfel
matrix without capturfng any
energy as ATP.
Transport of H+ across the mitochondrial
membrane by 2.4-dinitrophenol.
2. Halothane intoxication: Halothane is used in anesthesia.
3. Snake venom: Their phospholipases can disrupt the membrane.
4. Dicoumarol: clinically used as an anticoagulant
5. Calcium also acts as uncouplers.
6. Aspirin: It is one of the most famous uncouplers. This explains the fever that accompanies
toxic overdoses of these drugs.
9
