Atmospheric Oxidation and Antioxidants. Volume III

375 Pages·1993·6.06 MB·English

by  Gerald Scott (Auth.)

Atmospheric
Oxidation and
Antioxidants
VOLUME III
G. Scotty editor
Department of Chemical Engineering
and Applied Chemistry
Aston University
Aston Triangle
Birmingham B4 7ET
U.K.
ELSEVIER
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IX
PREFACE
Oxidation by molecular oxygen is one of the most practically important of
all chemical processes. It is the basis of energy production in animals and,
at the same time, a major cause of irreversible deterioration and ultimate
death. Man uses oxygen positively in the production of energy by combus-
tion, and many important industrial processes in the petrochemical in-
dustry are based on the controlled oxidation of hydrocarbons. At the same
time, oxidation is the main cause of deterioration of foodstuffs and of many
industrial polymers.
It is clearly of great practical importance that the mechanisms of oxida-
tion and its prevention should be understood in order to utilise the reactions
of oxygen more effectively but, equally importantly, to control the adverse
effects of oxygen on man-made products and in biological systems. The three
volumes of this work are directed toward these objectives. Volume I reviews
current understanding of autoxidation, largely on the basis of the reactions
of oxygen with characterised chemicals. From this flows the modern mech-
anisms of antioxidant action and their application in stabilisation technol-
ogy. Volume II examines the oxidation chemistry of carbon-based materials
in more detail with, emphasis on the technological phenomena that result
from the attack of oxygen and the practical procedures developed to prevent
them. Volume III addresses our present understanding of how oxidation is
involved both positively and negatively in life processes. This is a more
recent and rapidly developing aspect of oxidation chemistry and many of the
concepts still have to be proved by rigorous scientific investigation. Never-
theless, the mechanistic principles developed as a result of studies in vitro
over the years now provide the basis for understanding the complex oxida-
tion chemistry of life processes and its control by biological antioxidants.
The three volumes, although complementary to one another, form a single
whole and it is hoped that, by frequent cross-reference, the reader will be
enabled to utilise ideas and experience from other disciplines to enlighten
his own. The first edition of this work was published a quarter of a century
ago in a single volume. The increase in size of the second edition reflects the
growth of interest in the subject in the intervening period. Nevertheless, the
mechanisms outlined in the first edition still form the basis of our present
understanding of oxidation chemistry and there will therefore be frequent
reference to it in this edition.
GERALD SCOTT
XI
LIST OF AUTHORS
S. AL-MALAIKA (Volume I)
Department of Chemical Engineering and Applied Chemistry, Aston
University, Aston Triangle, Birmingham B4 7ET, U.K.
N.C. BILLINGHAM (Volume II)
School of Chemistry and Molecular Sciences, University of Sussex,
Brighton BN1 9QJ, U.K.
JOHN A. BLAIR (Volume III)
Pharmaceutical Sciences Institute, Aston University, Aston Triangle,
Birmingham B4 7ET, U.K.
E.B. BURLAKOVA (Volume III)
The Institute of Chemical Physics, Kosygin-str. 4, Moscow 117334,
Russia
G. CAMINO (Volume II)
Dipartimento di Chimica Inorganica, Università Degli Studi di Torino,
Via Pietro Giuria, 10125 Torino, Italy
DJ. CARLSSON (Volume II)
Division of Chemistry, National Research Council of Canada, Ottawa,
K1A 0R9, Canada
T. COLCLOUGH (Volume II)
Exxon Chemical Technology Centre, Abingdon, Oxon. 0X13 6BB, U.K.
NANCY E. DAVIDSON (Volume III)
Oncology Center, Johns Hopkins Medical Institutions, 615 N. Wolfe
Street, Baltimore, MD 21205, U.S.A.
H.H. DRAPER (Volume III)
Department of Nutritional Sciences, University of Guelph, Ontario,
Canada NIG 2W1
XU
H. BRIAN DUNFORD (Volume III)
Department of Chemistry, University of Alberta, Edmonton, Alberta,
Canada T6G 2G2
GILL FARRAR (Volume III)
Pharmaceutical Sciences Institute, Aston University, Aston Triangle,
Birmingham B4 7ET, U.K.
JOHN M.C. GUTTERIDGE (Volume III)
National Institute for Biological Standards and Control, Blanche Lane,
South Mimms, Potters Bar, Herts. EN6 3QG, U.K.
KATHRYN Z. GUYTON (Volume III)
Department of Environmental Health Sciences, Johns Hopkins
Medical Institutions, 615 N. Wolfe Street, Baltimore, MD 21205, U.S.A.
BARRY HALLIWELL (Volume III)
Department of Biochemistry, King's College (KQC), Strand Campus,
London WC2R 2LS, U.K.
THOMAS W. KENSLER (Volume III)
Department of Environmental Health Sciences and Department of
Pharmacology and Molecular Sciences, Johns Hopkins Medical
Institutions, 615 N. Wolfe Street, Baltimore, MD 21205, U.S.A.
S.P. KOCHHAR (Volume II)
SPK Consultancy Services, 48 Chiltern Crescent, Earley, Reading RG6
IAN, U.K
R.P. LATTIMER (Volume II)
The B.F. Goodrich Research and Development Center, Brecksville, OH
44141, U.S.A.
R.W. LAYER (Volume II)
The B.F. Goodrich Research and Development Center, Brecksville, OH
44141, U.S.A.
DIANA METODIEWA (Volume III)
Department of Chemistry, University of Alberta, Edmonton, Alberta,
Canada T6G 2G2
ETSUO NIKI (Volume III)
Department of Reaction Chemistry, The University of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113, Japan
Xlll
Z. OSAWA (Volume II)
Faculty of Engineering, Gunma University, Kiryu, Gunma 376, Japan
D.G. POBEDIMSKY (Volume III)
Russian Academy of Technological Sciences, Leninsky Prospect 9,
Moscow 117049, Russia
GREGORY A. REED (Volume III)
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, KS 66103, U.S.A.
C.K. RHEE (Volume II)
The Uniroyal Goodrich Tire Company, Brecksville, OH 44141, U.S.A.
TADEUSZ SARNA (Volume III)
Department of Biophysics, Institute of Molecular Biology, Jagiellonian
University, A. Mickiewicza 3, 21-120 Krakow, Poland
GERALD SCOTT (Volumes I, II and III)
Department of Chemical Engineering and Applied Chemistry, Aston
University, Aston Triangle, Birmingham B4 7ET, U.K.
HAROLD M. SWARTZ (Volume III)
University of Illinois, College of Medicine at Urbana-Champaign, 506
South Mathews, Urbana, IL 61801, U.S.A.
PAUL J. THORNALLEY (Volume III)
Department of Chemistry and Biological Chemistry, University of
Essex, Wivenhoe Park, Colchester C04 3SQ, Essex, U.K.
PETER WARDMAN (Volume III)
Cancer Research Campaign, Gray Laboratory, P.O. Box 100, Mount
Vernon Hospital, Northwood, Middlesex HA6 2JR, U.K.
1
Chapter 1
LIPID PEROXIDATION AND ITS INHIBITION
ETSUO NIKI
1. INTRODUCTION
There is increasing experimental and epidemiological evidence to show
that free radical-mediated peroxidations in biological systems with as-
sociated lipid peroxides are involved in a variety of pathological events
[1-28], cancer [29-34],and aging [35-41], Oxygen radicals are capable of
damaging nucleic acids, proteins and free amino acids, lipids and lipo-
proteins, carbohydrates, and connective tissue molecules. These species
may have an impact on such cell activities as membrane function, metabo-
lism and gene expression. However, the importance of direct involvement of
oxygen radicals in many disease processes is still controversial and it is not
clearly established whether lipid peroxidation is a major cause of tissue
injury or simply a consequence of it. Even if free radical-mediated lipid
peroxidations are not the primary cause of disorders, they may still be
important in causing more damage. In any event, it is essential to under-
stand the basic science of lipid peroxidation both in vitro and in vivo.
Furthermore, it is now well understood that the biological systems are
protected from such oxidative stress and free radical attack by an array of
defence systems [42-49]. An understanding of the function and mechanism
of biological and synthetic antioxidants is also important in understanding
oxygen and free radical-mediated tissue injury and in developing their
therapeutic usages.
Although the mechanism, rate and products of lipid peroxidation and its
inhibition in homogeneous solution have been elucidated, those for mem-
branes as well as biological systems are not yet well understood. This is
partly because of the inherent complexities of the membranes and their
biological environment, but also due to the lack of analytical methods with
sufficient reliability, specificity, and sensitivity. The objective of this Chap-
ter is to overview the state of the art of lipid peroxidation and its inhibition
in biological systems and in related model systems.
2 ETSUO NIKI
2. LIPIDS IN BIOMEMBRANES
Biological membranes are composed of lipids, proteins and carbohy-
drates. The lipids in the membranes must be the most important target of
free radicals. These include phospholipids, glycolipids and cholesterol.
Various phospholipids are found in the membranes, such as phosphatidic
acid (PA), phosphatidylglycerol (PG), cardiolipin (CL), phosphatidylcholine
(PC), lysolecithin (LPC), phosphatidylethanolamine (PE), phosphatidyl-
serine (PS), phosphatidylinositol (PI), and sphigomyelin (SM) whose struc-
tures are shown below.
O
Rx-C-O-CHg
Ro-C-0-CH O I
1 II I II
O CH -0-P-0-R
2 3
_0
R (base)
3
Phosphatidylcholine (PC) -CH -CH2-+N(CH )3
2 3
Phosphatidylethanolamine (PE) -CH -CH -+NH
2 2 3
Phosphatidylserine (PS) -CH -CH-3NH
2 3
coa
Phosphatidic acid (PA) -H
Phosphatidylglycerol (PG) —CHo—CH—CHo
2 I I 2
OH OH
O
II
Cardiolipin (CL) -CH2-CH-CH2-0-P-0-CH2-CH-CH20-C-R4
OH O O-C-R3 O
II
O
Phosphatidylinositol (PI) OH OH
OH
OH
LIPID PEROXIDATION AND ITS INHIBITION
TABLE 1
Phospholipid composition of rat hepatocytes (%)
PC LPC PE PS PI SM PA Others
Nucleic acid 57.3 26.1 5.5 3.9 6.3 tr 1.1
Mitochondrion 40.5 1.4 34.7 6.6 2.4 14.8
Microsome 59.1 2.0 24.1 9.2 4.2 1.0
Cell surface 43 2 20 4 6.5 23 2
membrane
Lysosome 41.9 2.9 20.5 5.9 16.0 12.9
LPC: lysolecithin; SM: sphingomyelin.
TABLE 2
Composition of human erythrocyte (wt %)
Proteins 49.2
Lipids 43.6
phospholipids (32.5)
PC 34.7
PE 28.0
PS 14.3
SM 20.1
PA 2.2
cholesterol (11.1)
Carbohydrates 7.2
The compositions of phospholipids in rat hepatocytes and red blood cell
membranes are shown in Tables 1 and 2 respectively. The phospholipids
contain much unsaturated fatty acid residues, which enhance the fluidity
and permeability of the membranes. These, and especially polyunsaturated
fatty acids which have two or more double bonds, are oxidized easily and
preferentially. In general, unsaturated fatty acids are more likely to be
found in R than in R of the phospholipids structure, I. Table 3 shows the
2 x
polyunsaturated fatty acids observed in the phospholipids. As discussed
later, these acid residues are the most oxidizable.
4 ETSUO NIKI
TABLE 3
Polyunsaturated fatty acids observed in the phospholipids
Carbon no. No. of double bond
Linoleic acid (Octadeca-9-,12-c/s-dienoic acid) 18 2
Linolenic acid (Octadeca-9-,12-,15-c/s-trienoic acid) 18 3
Arachidonicacid(Icosa-5-,8-,ll-,14-,c/s-tetraenoic 20 4
acid)
Docosahexanoicacid(Docosa-4-,7-,10-,13-,16-,19-c/s- 22 6
hexaenoic acid)
3. PEROXIDATIONS OF LIPIDS IN THE MEMBRANES.
The free radical-mediated peroxidations of lipids in the membranes
proceed by substantially the same sequence as that in the homogeneous
solution. As shown in Scheme 1, the peroxidation is composed of three steps,
that is, chain initiation, chain propagation and chain termination. In the
chain initiation step, the lipid radical L· is generated and initiates the chain
reaction. The lipid radical generally reacts with oxygen rapidly to give a
lipid peroxyl radical L0 ·, which in turn attacks another lipid molecule and
2
abstracts an active hydrogen to give lipid hydroperoxide and at the same
time another lipid radical. This radical also reacts with oxygen rapidly to
give a lipid peroxyl radical which attacks the lipid molecule. Thus, Reactions
(1) and (2) take place repeatedly to give lipid hydroperoxide as primary
product.
. 0 > L0 - (1)
L + 2 2
L0 - + LH > LOOH + L· (2)
2
In the chain termination step, the radicals disappear by mutual biomolecu-
lar interactions or by stabilization by an antioxidant.
The characteristic feature of free radical-mediated lipid peroxidation is
that it proceeds by a chain mechanism; that is, only one initiating radical
may induce chain oxidation and cause a number of lipids to be oxidized to
give lipid hydroperoxides. In other words, the kinetic chain length may be
much larger than 1. This must be very important since a single interaction
of a radical may not be so damaging but the following chain propagation
sequence must amplify the membrane damage. On the other hand, the
oxidation of lipids by non-radical species is not a chain reaction. For ex-
ample, singlet oxygen, one of the well known active oxygen species, is not a