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S e v e n t y Y e a r s of t h e Maillard Reaction
SIN'ITIRO KAWAMURA
Kagawa-ken Meizen Junior College, Kameoka 1-10, Takamatu, 760 Japan
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0097-6156/83/0215-0003$06.00/0
© 1983 American Chemical Society
amino-compounds p r o d u c e d f r o m p r o t e i n s a r e h e a t e d a t 120-140 C
w i t h s u g a r s s u c h as o r d i n a r y g l u c o s e o r m a l t o s e , w h i c h a r e
produced at t h i s stage of p r o c e s s , c o m b i n a t i o n o c c u r s . The
p r e c i s e n a t u r e o f t h e compounds p r o d u c e d i s unknown t o me, but
t h e y a r e p r o b a b l y g l u c o s a m i n e - l i k e b o d i e s . " He f u r t h e r
d e s c r i b e d the r e a c t i o n of h e a t i n g g l u c o s e w i t h a s p a r a g i n e ,
which produced darkening i n c o l o r .
C a r l Joseph Ludwig L i n t n e r (1855-1926), l e a d e r of the
S c i e n t i f i c S t a t i o n f o r Brewing ( W i s s e n s c h a f t l i c h e S t a t i o n fuer
B r a u e r e i ) i n M u n i c h was s t u d y i n g t h e f o r m a t i o n o f m a l t aroma.
He gave a l e c t u r e ( 6 ) a t t h e 3 6 t h M e e t i n g o f t h e S t a t i o n i n
November, 1912. As soon as he knew o f t h e r e p o r t o f M a i l l a r d
(2^), he made some e x p e r i m e n t s by t h e p r o c e s s o f M a i l l a r d ( n a c h
dem Vorgange v o n M a i l l a r d ) . He o b t a i n e d d a r k r e a c t i o n
p r o d u c t s w h i c h were r e s p o n s i b l e a l s o f o r f l a v o r and aroma ( c f .
7).
Ame P i c t e t (1857-1937) o f t h e U n i v e r s i t y o f Geneva
r e p o r t e d t h e f o r m a t i o n o f p y r i d i n e and i s o q u i n o l i n e b a s e s f r o m
a c i d h y d r o l y z a t e of c a s e i n i n the presence of formaldehyde i n
1916 ( 8 ) . M a i l l a r d ( 9 ) c l a i m e d p r i o r i t y o v e r him i n
d i s c o v e r i n g t h e c o n d e n s a t i o n o f amino a c i d s w i t h a l d e h y d e s o r
s u g a r s t o y i e l d p y r i d i n e b a s e s by c i t i n g h i s own p a p e r ( 1 0 ) .
We s h o u l d n o t e t h a t W o r l d War I went on f r o m J u l y 1914 t o
November 1918; S w i s s s c i e n t i s t s c o u l d c o n t i n u e r e s e a r c h ,
whereas F r e n c h ones c o u l d n o t do so e a s i l y .
L o u i s - C a m i l l e M a i l l a r d was b o r n on F e b r u a r y 4, 1878 i n
P o n t - a - M o u s s o n (Meuthe e t M o s e l l e ) (48.55°N , 6.03°E). He went
to Nancy, where he o b t a i n e d t h e d e g r e e s o f M. S c . i n 1897 and
Dr. Med. i n 1903. T h e r e a f t e r he worked i n t h e C h e m i c a l
D i v i s i o n o f t h e S c h o o l o f M e d i c i n e , U n i v e r s i t y o f Nancy. In
1914 he moved t o P a r i s and t h e young d o c t o r worked as head o f a
b i o l o g i c a l group i n t h e C h e m i c a l L a b o r a t o r y , U n i v e r s i t y o f
Paris (7).
In 1911 h i s f i r s t r e p o r t (3») on p e p t i d e s y n t h e s i s was
p r e s e n t e d and i n 1912 h i s f i r s t r e p o r t ( 2 ) on t h e s u g a r - a m i n o
a c i d r e a c t i o n was p u b l i s h e d . He c o m p l e t e d a book (1_1) i n 1913.
A f t e r W o r l d War I i n 1919 he was a p p o i n t e d p r o f e s s o r o f
b i o l o g i c a l and m e d i c a l c h e m i s t r y a t t h e U n i v e r s i t y o f A l g i e r s .
In t h e same y e a r he became a c o r r e s p o n d i n g member o f t h e
D i v i s i o n o f Pharmacy, Academy of M e d i c i n e .
In May 1936 he was i n v i t e d t o P a r i s f o r a l e c t u r e . On
t h a t t h e y p u b l i s h e d r e v i e w a r t i c l e s w i t h t h e s e words i n t h e
title. However, I wondered i f any o t h e r w o r k e r u s e d t h e t e r m
Maillard reaction earlier.
E x a m i n a t i o n of the s u b j e c t indexes of Chemical A b s t r a c t s
(CA) r e s t r i c t e d t o t h e terms b r o w n i n g and M a i l l a r d r e a c t i o n
gave t h e r e s u l t s shown i n T a b l e I .
Thus CA a l r e a d y u s e d t h e i n d e x t e r m M a i l l a r d r e a c t i o n i n t h e
5 t h C o l l e c t i v e I n d e x ( 1 9 4 7 - 5 6 ) , p r i o r t o 1959. There was no
i n d e x t e r m M a i l l a r d r e a c t i o n up t o v o l . 43 (1949) o f CA. The
e a r l i e s t c i t a t i o n s by t h a t t e r m a r e t o t h e 6 p a p e r s (27-32) i n
CA 44 (1950) and 46-48 ( 1 9 5 2 - 5 4 ) .
J o h n B. Thompson (21) worked a t t h e T r a c e M e t a l R e s e a r c h
L a b o r a t o r i e s i n C h i c a g o , w h i l e Andre P a t r o n (28) was employed
a t t h e I n s t i t u t e o f C o l o n i a l F r u i t s and C i t r u s e s ( I n s t i t u t e de
F r u i t s e t Agrumes C o l o n i a u x ) i n P a r i s , and p r e p a r e d a r e v i e w
( 3 3 ) c o n t a i n i n g t h e words M a i l l a r d r e a c t i o n i n t h e t i t l e . R.
G e o f f r o y (29) o f t h e F r e n c h C o l l e g e o f M i l l i n g ( E c o l e Française
de M e u n e r i e ) i n P a r i s a l s o p u b l i s h e d a b r i e f r e v i e w on t h e
M a i l l a r d r e a c t i o n i n the c e r e a l i n d u s t r y . H. L. A. T a r r (30)
o f P a c i f i c F i s h e r i e s S t a t i o n , V a n c o u v e r , B r i t i s h C o l u m b i a , as
w e l l as Hans Wegner (3_2) o f t h e R e s e a r c h I n s t i t u t e o f S t a r c h
F a b r i c a t i o n ( F o r s c h u n g s i n s t i t u t der S t a e r k e f a b r i k a t i o n ) i n
B e r l i n , a l s o used t h i s term i n the t i t l e s of r e s e a r c h papers.
Chemistry of the M a i l l a r d R e a c t i o n
r a f f i n o s e , and s t a c h y o s e ) t e n d e d t o d e c r e a s e . These
n o n r e d u c i n g s u g a r s were presumed t o u n d e r g o h y d r o l y s i s upon
h e a t i n g , and r e d u c i n g s u g a r s formed ( f r u c t o s e , g l u c o s e , and
g a l a c t o s e ) were r e s p o n s i b l e f o r t h e M a i l l a r d r e a c t i o n .
1 5
S t u d i e s w i t h N - n o n d i a l y z a b l e m e l a n o i d i n showed t h a t 76%
of t h e d i e t a r y m e l a n o i d i n was e x c r e t e d i n r a t s ' f e c e s ( 5 9 ) .
The o r a l a d m i n i s t r a t i o n o f M a i l l a r d r e a c t i o n p r o d u c t s c a u s e d an
i n c r e a s e i n t h e g r o w t h o f b o t h a e r o b i c and a n a e r o b i c
l a c t o b a c i l l i i n the m i c r o f l o r a of r a t s ( 6 0 ) .
M u t a g e n i c i t y of M a i l l a r d R e a c t i o n Products
I n a d v a n c e d s t a g e s o f t h e M a i l l a r d r e a c t i o n some mutagens
m i g h t be f o r m e d . F o r e x a m p l e , mutagens a p p e a r e d when g r o u n d
b e e f hamburgers were c o o k e d o v e r 200°C ( c f . 41)· Reductive
i n t e r m e d i a t e s i s o l a t e d from b r o w n i n g m i x t u r e s o f t r i o s e
r e d u c t o n e w i t h g u a n i n e and i t s d e r i v a t i v e s a l s o showed
mutagenicity (61).
Japanese workers i n the N a t i o n a l Cancer Center Research
I n s t i t u t e p u b l i s h e d r e v i e w s c o n c e r n i n g mutagens i n h e a t e d f o o d s
(62-64). P y r o l y z a t e s o f p r o t e i n s , p e p t i d e s , and amino a c i d s ,
e s p e c i a l l y t r y p t o p h a n and g l u t a m i c a c i d , showed m u t a g e n i c i t y
(65-69). C o f f e e p r e p a r e d i n t h e u s u a l way f o r d r i n k i n g
c o n t a i n e d some m u t a g e n i c s u b s t a n c e ( s ) ( 7 0 ) . B l a c k t e a and
g r e e n t e a were a l s o m u t a g e n i c . However, t h e s e f a v o r i t e
b e v e r a g e s were n o t c a r c i n o g e n i c ( 6 4 ) . N i n e h e t e r o c y c l i c amines
were i s o l a t e d as m u t a g e n i c compounds f r o m p y r o l y z a t e s ( 6 3 ) :
two p y r i d o i n d o l e s , f o u r p y r i d o i m i d a z o l e s , two i m i d a z o -
q u i n o l i n e s , and 2 - a m i n o - 5 - p h e n y l p y r i d i n e . None o f them have
been i s o l a t e d as p r o d u c t s o f t h e M a i l l a r d r e a c t i o n . Moreover,
m u t a g e n i c i t y a p p e a r e d o n l y above 400°, and even more s t r o n g l y
a t 500-600°C as t h e p y r o l y s i s t e m p e r a t u r e .
L e e , e_t a _ l . (_71) c a r r i e d out l o n g - t e r m (up t o 12 months)
f e e d i n g e x p e r i m e n t s o f browned egg a l b u m i n w i t h r a t s . Several
changes were f o u n d , b u t no m u t a g e n i c r e s p o n s e was o b s e r v e d .
A s i m p l e s k e t c h i s g i v e n a l o n g t h e l i n e s o f two r e c e n t
r e v i e w s (^2> 73_). B o r s o o k , e t a l . (74) o b s e r v e d t h e o c c u r r e n c e
of A m a d o r i compounds i n v i v o , w h i c h were c o n f i r m e d by Heyns and
P a u l s e n (75) t o be 1-deoxy-l-N-aminoacy1-D-fructose
derivatives. F e e n e y , e t a _ l . (76) i n c u b a t e d g l u c o s e w i t h egg
w h i t e a t 37°C f o r a few days and o b s e r v e d t h e d i s a p p e a r a n c e o f
glucose. H o l m q u i s t and S c h r o e d e r (JJ) f i r s t showed t h a t t h e
N - t e r m i n a l v a l i n e of H b - A - l - c was b l o c k e d and s u b s e q u e n t
r e s e a r c h e r s showed t h e o c c u r r e n c e o f A m a d o r i r e a r r a n g e m e n t o f
an a l d o s y l a m i n e , N - ( 1 - d e o x y g l u c o s y l ) v a l i n e . Rahbar (78)
d i s c o v e r e d an i n c r e a s e i n t h e m i n o r h e m o g l o b i n component,
Hb-A-l-c, i n the blood of d i a b e t i c p a t i e n t s .
T a n z e r (7_9) o b s e r v e d the p r e s e n c e of t h e r e d u c e d f o r m of
t h e A m a d o r i compounds formed w i t h h y d r o x y l y s i n e and reducing
s u g a r s i n aged c o n n e c t i v e t i s s u e s . M e s t e r , e_t a l _ . (80)
s u g g e s t e d the f o r m a t i o n of A m a d o r i compounds i n the b l o o d f r o m
g l u c o s e and l y s i n e - r i c h p r o t e i n o r s e r o t o n i n e . C e r a m i , eit
3^.(81) showed t h a t i n d i a b e t e s m e l l i t u s s t r u c t u r a l p r o t e i n s of
t h e l e n s m i g h t be a f f e c t e d by h i g h g l u c o s e c o n c e n t r a t i o n t o
induce c a t a r a c t through Amadori-type r e a c t i o n . It is likely
t h a t t h i s k i n d of s t u d y has not been made by J a p a n e s e w o r k e r s .
M a i l l a r d Reaction i n R e l a t i o n to L i p i d s
L i p i d s upon a u t o x i d a t i o n p r o d u c e c a r b o n y l compounds, w h i c h
r e a c t w i t h amino compounds t o f o r m brown h i g h - m o l e c u l a r
products. T h i s t y p e of b r o w n i n g has r e c e n t l y been r e v i e w e d by
P o k o r n y (82^). A c c o r d i n g t o him the f i r s t p a p e r on the s u b j e c t
was p u b l i s h e d by S t a n s b y ( 8 3 ) . F u j i m o t o , e t a l . (84-89)
s t u d i e d t h i s r e a c t i o n w i t h some f i s h and r e p o r t e d t h a t most
brown p i g m e n t of f i s h m u s c l e was s o l u b l e i n b e n z e n e - m e t h a n o l .
Thus i n t h i s c a s e o x i d i z e d l i p i d - p r o t e i n i n t e r a c t i o n s a r e more
i m p o r t a n t t h a n the r e a c t i o n between amino a c i d s and r i b o s e . In
f i s h m u s c l e the b r o w n i n g due t o o x i d i z e d l i p i d s i s a c c o m p a n i e d
by the M a i l l a r d r e a c t i o n between amino a c i d s and r i b o s e . In
t h i s c o n n e c t i o n i t i s i n t e r e s t i n g t o n o t e an e a r l i e r g a p e r by
T a r r ( 3 0 ) , who r e p o r t e d t h a t upon h e a t i n g 1 h r a t 120 C h a l i b u t
browned s l i g h t l y whereas l i n g c o d d a r k e n e d m a r k e d l y and t h a t
f r e e r i b o s e was d e t e c t e d i n the l a t t e r f i s h m u s c l e .
M a i l l a r d r e a c t i o n p r o d u c t s have a n t i o x i d a n t a c t i v i t y ( 9 0 ,
91). F r a n z k e and I w a i n s k y (92) f i r s t r e p o r t e d t h i s a c t i v i t y of
melanoidins. P a t t o n (93) n o t e d the c o n t r i b u t i o n of the
M a i l l a r d r e a c t i o n i n p r e v e n t i n g d r y m i l k powder f r o m o x i d a t i o n .
G r i f f i t h and J o h n s o n (94) showed t h a t the p r o d u c t s from
r e a c t i o n of g l u c o s e and g l y c i n e e x h i b i t e d a n t i o x i d a t i v e
p r o p e r t i e s i n model s y s t e m w i t h l a r d . The a n t i o x i d a t i v e
p r o p e r t i e s were a t t r i b u t e d t o r e d u c t o n e s and t h i s was p r o v e d by
E v a n s , et_ a l . ( 9 5 ) . Z i p s e r and W a t t s (£6) r e p o r t e d t h a t
s t e r i l i z a t i o n o f meat p r o d u c e d a n t i o x i d a t i v e compounds by t h e
Maillard reaction. Y a m a g u c h i , e_t a_l. (91) as w e l l as K i r i g a y a ,
e t a l . (98) made e x t e n s i v e s t u d i e s c o n c e r n i n g t h i s p r o b l e m .
E i c h n e r (90) s t u d i e d i n t e r m e d i a t e r e d u c t o n e - l i k e compounds as
antioxidants. Y a m a g u c h i , e t a l . (99) f r a c t i o n a t e d the r e a c t i o n
p r o d u c t s o b t a i n e d by h e a t i n g D - x y l o s e and g l y c i n e and f o u n d
s t r o n g a n t i o x i d a t i v e a c t i v i t y i n some m e l a n o i d i n f r a c t i o n s .