Biochemical Adaptations in Skeletal Muscle Induced by Exercise

2 Biochemical Adaptations in Skeletal Muscle Induced by Exercise Training Ronald L. Terjung and David A. Hood

Downloaded by FUDAN UNIV on December 29, 2016 | http://pubs.acs.org Publication Date: December 3, 1986 | doi: 10.1021/bk-1986-0294.ch002

Department of Physiology, Upstate Medical Center, State University of New York, Syracuse, NY 13210

Exercise performance seems to be greatly affected by the chronic level of physical activity experienced by the animal or individual. For example, differences in the capacity for prolonged exercise seem obvious between wild and domesticated animals. This is probably due, in part, to inherent biochemical differences between the muscles of active and less active species (1). Muscles of wild animals appear darker than those of their domesticated counterparts (2). Further, variations in activity patterns due to seasonal change (3) or hibernation (4), are associated with differences in the enzymes related to oxidative metabolism. Thus, in a general sense physical activity seems to be associated with biochemical changes that enhance the muscle's capacity for aerobic metabolism. Muscle Adaptations The specific biochemical changes induced by increased physical activity are well characterized from laboratory studies and have been the subject of a number of excellent reviews (5-9). The fundamental change found in skeletal muscle after exercise training is an enhanced capacity for energy provision via aerobic metabolism. There i s an i n c r e a s e i n m i t o c h o n d r i a l p r o t e i n content and c r i s t a e component enzymes a s s o c i a t e d w i t h t h e e l e c t r o n t r a n s p o r t . In a thorough s t u d y , H o l l o s z y (10) found t h a t an e x e r c i s e program o f p r o l o n g e d t r e a d m i l l r u n n i n g i n c r e a s e d the m i t o c h o n d r i a l content o f l a b o r a t o r y r a t s by a p p r o x i m a t e l y 100%. S i m i l a r t r a i n i n g responses are found i n a wide v a r i e t y o f o t h e r animals i n c l u d i n g man (9,11). Subsequent m o r p h o l o g i c a l s t u d i e s have shown t h a t the m i t o c h o n d r i a o f t r a i n e d muscles appear t o be more abundant (12) and l a r g e r (13). Thus, t h e c r o s s - s e c t i o n o f the t r a i n e d muscle appears more d e n s e l y packed w i t h m i t o c h o n d r i a . M i t o c h o n d r i a i s o l a t e d from muscles o f t r a i n e d animals e x h i b i t the same dependence on ADP t o s t i m u l a t e and i n c r e a s e r e s p i r a t i o n , and a r e as e f f i c i e n t i n t h e c o u p l i n g o f ATP p r o d u c t i o n t o oxygen consumption as muscle o b t a i n e d from s e d e n t a r y animals (10). Thus, the i n c r e a s e d m i t o c h o n d r i a l content r e p r e s e n t s a t r u e i n c r e a s e i n the p o t e n t i a l f o r a e r o b i c ATP g e n e r a t i o n w i t h i n the muscle. I n a d d i t i o n t o the g r e a t e r e l e c t r o n t r a n s p o r t c a p a c i t y , t h e r e i s a l s o a c o o r d i n a t e d i n c r e a s e i n t h e enzymes o f support 0097-6156/ 86/ 0294-0008$06.00/ 0 © 1986 American Chemical Society

Layman; Nutrition and Aerobic Exercise ACS Symposium Series; American Chemical Society: Washington, DC, 1986.

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systems necessary t o s u p p l y the r e d u c i n g e q u i v a l e n t s f o r the e l e c t r o n t r a n s p o r t and ATP s y n t h e s i s . Thus, the c a p a c i t i e s f o r carboh y d r a t e o x i d a t i o n ( 1 4 ) , f a t t y a c i d o x i d a t i o n (15,16), k e t o n e body o x i d a t i o n ( 1 7 ) , t r i c a r b o x y l i c a c i d c y c l e enzymes ( 1 8 ) , and m i t o c h o n d r i a l s h u t t l e pathways (19) are i n c r e a s e d by endurance t r a i n i n g . I n a d d i t i o n , the content of m y o g l o b i n , w h i c h i s thought t o f a c i l i t a t e oxygen t r a n s f e r w i t h i n the c e l l (20,21), i n c r e a s e s i n the t r a i n e d muscle ( 2 , 2 2 ) . Thus, t h e r e i s a c o o r d i n a t e d i n c r e a s e i n the c a p a c i t y of the t r a i n e d muscle f o r ATP p r o v i s i o n v i a o x i d a t i v e metabolism. These changes c o n t r i b u t e to the d a r k e r appearing muscles of the t r a i n e d a n i m a l s . The p r i m a r y m e t a b o l i c s i g n i f i c a n c e of the enhanced a e r o b i c c a p a c i t y i s p r o b a b l y r e l a t e d t o the c o n t r o l of energy metabolism and a s h i f t i n s u b s t r a t e source from carboh y d r a t e to f a t i n the muscles d u r i n g submaximal e x e r c i s e (6,8,23). S p e c i f i c i t y of

Adaptations

The b i o c h e m i c a l a d a p t a t i o n s t o e x e r c i s e t r a i n i n g are v e r y s p e c i f i c to the w o r k i n g m u s c l e s . F o r example, an i n c r e a s e i s found i n the h i n d l i m b muscle of t r e a d m i l l run r a t s , but not i n l i v e r (24) o r the l e s s a c t i v e abdominal muscles of the same animals ( 2 2 ) . Further, when a unique t r a i n i n g program t h a t e x e r c i s e s o n l y one l i m b on a c y c l e ergometer i s employed, the a d a p t a t i o n i s induced i n the e x e r c i s e d l e g , but not the u n t r a i n e d c o n t r a l a t e r a l l e g ( 1 3 , 2 5 ) . Thus, the t r a i n i n g a d a p t a t i o n i s not a g e n e r a l i z e d response w i t h i n the i n d i v i d u a l . T h i s i n d i c a t e s t h a t the s t i m u l u s r e s p o n s i b l e f o r b r i n g i n g about the b i o c h e m i c a l change i s s p e c i f i c t o the w o r k i n g muscle and r e l a t e d t o the demands p l a c e d upon the muscle by the exercise effort. F a c t o r s t h a t determine the magnitude of the t r a i n i n g e f f e c t are f a i r l y complex, due i n p a r t t o the o r d e r e d p a t t e r n of motor u n i t r e c r u i t m e n t found d u r i n g normal l o c o m o t i o n and/or a s p e c i f i c work t a s k . The type and i n t e n s i t y of the e x e r c i s e e f f o r t l a r g e l y d e t e r mine w h i c h motor u n i t s w i l l be u t i l i z e d t o p e r f o r m the work ( 2 6 ) . Each motor u n i t w i t h i n a muscle i s composed of a s i n g l e nerve axon and the muscle f i b e r s t h a t i t i n n e r v a t e s . W h i l e a l l f i b e r s w i t h i n a g i v e n motor u n i t have the same p r o p e r t i e s , i t i s now r e c o g n i z e d t h a t at l e a s t t h r e e d i f f e r e n t s k e l e t a l muscle f i b e r types (and thus motor u n i t s ) e x i s t i n mammals. They d i f f e r c o n s i d e r a b l y i n t h e i r c o n t r a c t i l e c h a r a c t e r i s t i c s , i n t h e i r inherent biochemical c a p a b i l i t i e s , and p r o b a b l y i n t h e i r response to t r a i n i n g . Thus, i t i s i m p o r t a n t to c o n s i d e r the impact of the d i f f e r e n t types of s k e l e t a l muscle motor u n i t s . M u s c l e F i b e r Types Mammalian s k e l e t a l muscle can be s e p a r a t e d i n t o two d i s t i n c t f i b e r p o p u l a t i o n s , based on r e l a t i v e c o n t r a c t i o n c h a r a c t e r i s t i c s , and are r e f e r r e d t o as s l o w - t w i t c h (Type I ) o r f a s t - t w i t c h (Type I I ) f i b e r s . The s l o w - t w i t c h f i b e r type e x h i b i t s a r e l a t i v e l y low s h o r t e n i n g v e l o c i t y ( 2 7 ) , a low r a t e of t e n s i o n development ( 2 7 ) , a low myosin ATPase a c t i v i t y (28) and a low r a t e of c a l c i u m s e q u e s t r a t i o n by the sarcoplasmic reticulum (29). The c o n v e r s e i s t r u e f o r the f a s t twitch fibers. Since c o n t r a c t i o n v e l o c i t y h i g h l y c o r r e l a t e s w i t h myosin ATPase a c t i v i t y ( 3 0 ) , i t i s p o s s i b l e t o e a s i l y i d e n t i f y ,



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w i t h i n a muscle c r o s s - s e c t i o n , f a s t and s l o w - t w i t c h f i b e r s by the i n t e n s i t y of s t a i n i n g of the myosin ATPase u s i n g h i s t o c h e m i c a l p r o c e d u r e s ( 3 1 ) . The s l o w - t w i t c h f i b e r s are c h a r a c t e r i s t i c a l l y r e d i n appearance, i n d i c a t i v e of a r e l a t i v e l y h i g h m i t o c h o n d r i a l content (14), e x h i b i t a h i g h b l o o d f l o w (32,33), and have a low g l y c o g e n o l y t i c c a p a c i t y (e.g., phosphorylase a c t i v i t y ) (7,34). The fastt w i t c h f i b e r s u n i f o r m l y possess a r e l a t i v e l y h i g h g l y c o g e n o l y t i c c a p a c i t y ( 7 , 3 4 ) , but can be s u b d i v i d e d by t h e i r c o n t r a s t i n g c a p a c i t i e s f o r o x i d a t i v e m e t a b o l i s m . I n f a c t , the g r e a t e s t d i f f e r e n c e i n m i t o c h o n d r i a l content f o r most non-primate mammalian muscle i s found between the f a s t - t w i t c h red and the f a s t - t w i t c h w h i t e f i b e r types (14,35). I n humans, the m i t o c h o n d r i a l content of s l o w - t w i t c h r e d f i b e r s i s t y p i c a l l y g r e a t e r than t h a t of the f a s t - t w i t c h r e d f i b e r s (7,35). S i m i l a r l y , measurements of b l o o d f l o w s t o s e c t i o n s of m u s c l e , which are p r i m a r i l y composed of a s i n g l e f i b e r t y p e , e x h i b i t l a r g e d i f f e r e n c e s c o n s i s t e n t w i t h the expected demands of oxygen s u p p l y based on m i t o c h o n d r i a l content (32,33). Thus, mammalian s k e l e t a l muscle i s t y p i c a l l y comprised of t h r e e b i o c h e m i c a l l y and f u n c t i o n a l l y d i s t i n c t f i b e r types: s l o w - t w i t c h r e d , f a s t - t w i t c h r e d and f a s t - t w i t c h w h i t e . These f i b e r types are a l s o commonly r e f e r r e d to as Type I , Type l i a , and Type l i b , r e s p e c t i v e l y (7). C o n t r a c t i o n p e r f o r m a n c e of t h e s e d i f f e r e n t f i b e r t y p e s i s p r e d i c t a b l e from a knowledge of t h e i r b i o c h e m i c a l and b l o o d f l o w differences. F o r example, the s l o w - t w i t c h r e d f i b e r type can cont r a c t f o r l o n g p e r i o d s of time w i t h o u t a l o s s i n t e n s i o n development (36). A l t h o u g h the r e l a t i v e l y h i g h f u n c t i o n a l a e r o b i c c a p a c i t y must be important f o r s u s t a i n e d performance ( 3 7 ) , i t i s a l s o known t h a t the s l o w - t w i t c h f i b e r type r e q u i r e s l e s s energy t o m a i n t a i n t e n s i o n (38). T h e r e f o r e , t h i s f i b e r type seems w e l l - s u i t e d f o r p r o l o n g e d s u s t a i n e d a c t i v i t y such as t h a t r e q u i r e d f o r p o s t u r a l s u p p o r t . The f a s t - t w i t c h red muscle f i b e r i s f a i r l y f a t i g u e r e s i s t a n t and capable of repeated powerful contractions before tension development declines s i g n i f i c a n t l y (36). A l t h o u g h t h i s f i b e r type has a h i g h c a p a c i t y f o r l a c t a t e p r o d u c t i o n ( 3 9 , 4 0 ) , i t s performance d u r i n g p r o l o n g e d c o n t r a c t i o n p e r i o d s i s made p o s s i b l e by i t s r e l a t i v e l y h i g h f u n c t i o n a l a e r o b i c c a p a c i t y ( 4 0 ) . I n c o n t r a s t , the f a s t - t w i t c h w h i t e muscle f i b e r e x h i b i t s a r a p i d l o s s of t e n s i o n development and i s capable of p o w e r f u l c o n t r a c t i o n s f o r o n l y a b r i e f p e r i o d of time (36). A h i g h r a t e of g l y c o g e n o l y s i s , r e s u l t i n g i n a h i g h l a c t a t e content and c e l l u l a r a c i d o s i s , would be found d u r i n g i n t e n s e cont r a c t i o n c o n d i t i o n s i n t h i s f i b e r type ( 4 1 ) . The s l o w - t w i t c h muscle f i b e r s are r e l a t i v e l y s m a l l i n d i a m e t e r and belong to motor u n i t s t h a t are t y p i c a l l y the f i r s t t o be r e c r u i t e d d u r i n g any motor t a s k . Thus, d u r i n g s i m p l e muscle a c t i v i t y r e q u i r e d f o r p o s t u r a l support of s t a n d i n g , the s l o w - t w i t c h motor u n i t s are v e r y a c t i v e and, i n some c a s e s , f u n c t i o n near t h e i r maxi m a l f o r c e output ( 4 2 ) . The f a s t - t w i t c h red f i b e r s belong t o l a r g e r motor u n i t s (26) and are r e c r u i t e d f o r muscle a c t i o n s t h a t are more f o r c e f u l (42). T h e i r r e c r u i t m e n t i n c r e a s e s , f o r example, when r u n n i n g at i n c r e a s i n g speeds on a t r e a d m i l l ( 4 2 ) . F i n a l l y , the f a s t - t w i t c h w h i t e f i b e r s belong t o l a r g e p o w e r f u l motor u n i t s and a r e r e c r u i t e d d u r i n g v e r y i n t e n s e e x e r c i s e (43,44) o r d u r i n g ext r e m e l y f o r c e f u l movements such as jumping ( 4 2 ) . The r e l a t i v e l y i n f r e q u e n t and s p e c i a l i z e d u t i l i z a t i o n of the f a s t - t w i t c h w h i t e motor u n i t s i s e s p e c i a l l y p u r p o s e f u l , s i n c e these i n t e n s e e x e r c i s e



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e f f o r t s and e x p l o s i v e body movements are u s u a l l y s h o r t l i v e d . Thus, the r a p i d f a t i g u e and r e l a t i v e l y poor endurance performance of t h i s f i b e r type (36) do not g e n e r a l l y i n f l u e n c e muscle f u n c t i o n d u r i n g moderate e x e r c i s e of submaximal i n t e n s i t y (43,44)« Athough t h e r e can be a s i g n i f i c a n t o v e r l a p i n the p r o g r e s s i v e r e c r u i t m e n t of motor u n i t p o p u l a t i o n s as the i n t e n s i t y of e x e r c i s e becomes g r e a t e r , the g e n e r a l p a t t e r n of o r d e r e d r e c r u i t m e n t from s l o w - t w i t c h red t o f a s t - t w i t c h red and then to f a s t - t w i t c h w h i t e motor u n i t s o c c u r s d u r i n g most p h y s i c a l a c t i v i t y ( 4 5 ) . The s k e l e t a l musculature of those non-primate mammals t h a t have been examined i s comprised p r i m a r i l y of ( i . e . , 80-95%) f a s t - t w i t c h f i b e r s (46,47). The f a s t t w i t c h f i b e r s a r e , i n t u r n , comprised of a p p r o x i m a t e l y equal p o r t i o n s of f a s t - t w i t c h red and f a s t - t w i t c h w h i t e f i b e r s . In contrast the s k e l e t a l muscle of man i s comprised of a p p r o x i m a t e l y 50% f a s t t w i t c h and 50% s l o w - t w i t c h muscle ( 7 , 4 8 ) . A l t h o u g h the l o w - o x i d a t i v e f a s t - t w i t c h w h i t e muscle f i b e r s are found i n humans ( 7 , 4 9 ) , they t y p i c a l l y r e p r e s e n t a s m a l l e r f r a c t i o n of the l i m b m u s c u l a t u r e as compared t o most lower mammals. I n summary, a l l mammals possess a l a r g e f r a c t i o n of h i g h - o x i d a t i v e muscle. The ordered p a t t e r n of motor u n i t r e c r u i t m e n t i n v o l v e s these h i g h o x i d a t i v e muscle f i b e r s b e f o r e the l o w - o x i d a t i v e f i b e r s , as e x e r c i s e i n t e n s i t y p r o g r e s s e s from m i l d , t o moderate, t o s e v e r e . T h i s p r o g r e s s i o n f a v o r s an enhanced e x e r c i s e performance a t submaximal e x e r c i s e i n t e n s i t i e s , s i n c e the slow and f a s t - t w i t c h r e d f i b e r s are capable of repeated c o n t r a c t i o n s f o r l o n g p e r i o d s of time. Important

T r a i n i n g Parameters

S e v e r a l i m p o r t a n t t r a i n i n g v a r i a b l e s are known t o i n f l u e n c e the magnitude of the b i o c h e m i c a l response. These i n c l u d e the d u r a t i o n of the t r a i n i n g program, the i n t e n s i t y of the e x e r c i s e e f f o r t , the d u r a t i o n of each e x e r c i s e bout ( m i n u t e s / d a y ) , and the f r e q u e n c y of e x e r c i s e ( i . e . , days/week). Training Duration. I t i s i n t u i t i v e l y obvious t h a t the d u r a t i o n of t r a i n i n g must be s u f f i c i e n t l y l o n g f o r the maximal response t o be developed. T h i s i s due, i n p a r t , to the n a t u r e of most t r a i n i n g programs t h a t t y p i c a l l y p r o g r e s s from r e l a t i v e l y m i l d or moderate e x e r c i s e e f f o r t s t o the more i n t e n s e e x e r c i s e bouts t h a t w i l l be m a i n t a i n e d t h e r e a f t e r . Thus, the c e l l u l a r s t i m u l u s f o r a d a p t a t i o n i s p r o b a b l y c o n t i n u a l l y changing u n t i l the peak e x e r c i s e e f f o r t , t h a t w i l l be r o u t i n e l y s u s t a i n e d f o r the steady s t a t e t r a i n i n g program, i s a c h i e v e d . A f t e r t h i s time the f u l l t r a i n i n g response might be e x p e c t e d . However, t h e r e i s an a d d i t i o n a l time d e l a y b e f o r e r e a l i z i n g the f u l l a d a p t i v e change. T h i s a d d i t i o n a l time i s due t o the c e l l u l a r events a s s o c i a t e d w i t h the a d a p t i v e response w i t h i n the c e l l . I n the case of a b i o c h e m i c a l change of an i n c r e a s e i n m i t o c h o n d r i a l p r o t e i n , the f u l l y developed response, r e p r e s e n t i n g the steady s t a t e change w i t h i n the muscle f i b e r , i s dependent upon the c e l l u l a r dynamics of p r o t e i n t u r n o v e r . S p e c i f i c a l l y , the r a t e at w h i c h a new steady s t a t e c o n c e n t r a t i o n of m i t o c h o n d r i a o c c u r s w i t h i n the muscle i s dependent upon the d e g r a d a t i o n r a t e c o n s t a n t of the m i t o c h o n d r i a l components ( 5 0 ) . Since p r o t e i n degradation i s a f i r s t - o r d e r p r o c e s s , the time course of m i t o c h o n d r i a l c o n t e n t change



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i s n o n - l i n e a r and i s c o n v e n i e n t l y c o n s i d e r e d i n terms of h a l f - l i f e . I n t h i s c o n t e x t , the h a l f - l i f e can be c o n s i d e r e d as the time r e q u i r e d f o r the m i t o c h o n d r i a l content t o proceed through o n e - h a l f the change, from the e x i s t i n g v a l u e , toward the new steady s t a t e v a l u e determined by the t r a i n i n g s t i m u l u s . A l t h o u g h i t i s p r o b a b l e t h a t the t u r n o v e r of m i t o c h o n d r i a does not o c c u r at the same r a t e i n a l l muscle f i b e r types ( 5 1 ) , an average h a l f - l i f e of a p p r o x i m a t e l y 1 week i s a r e a s o n a b l e v a l u e f o r mixed muscle of animals (52,53) and man ( 5 4 ^ . Thus, even i f the c e l l u l a r s t i m u l u s , s u f f i c i e n t to i n c r e a s e cytochrome c t o double t h a t n o r m a l l y found, were t o o c c u r i n s t a n t a n e o u s l y and remain c o n s t a n t t h e r e a f t e r , o n l y o n e - h a l f of the response would be measured when t r a i n i n g proceeded f o r the next week. T r a i n i n g the subsequent week would then produce a n o t h e r o n e - h a l f of the e f f e c t , t o b r i n g the response t o 75% c o m p l e t i o n . Each subsequent h a l f - l i f e d u r a t i o n would b r i n g about o n e - h a l f of the remaining e f f e c t . I t would then take a p p r o x i m a t e l y 5 h a l f - l i v e ( a p p r o x i m a t e l y 5 weeks) t o r e a l i z e n e a r l y 95% of the new steady s t a t e response. Thus, a s s e s s i n g the t r a i n i n g response b e f o r e at l e a s t 5-6 weeks, a f t e r a c h i e v i n g a f u l l t r a i n i n g program, w i l l always tend t o u n d e r e s t i m a t e the t r u e magnitude of the b i o c h e m i c a l change w i t h i n the w o r k i n g muscles. T h i s i l l u s t r a t e s the need f o r the t r a i n i n g d u r a t i o n to be s u f f i c i e n t l y p r o l o n g e d f o r the a d a p t i v e change t o f u l l y d e v e l o p . The f i r s t - o r d e r n a t u r e of t h i s p r o c e s s r a i s e s an i m p o r t a n t a s p e c t w i t h r e g a r d t o d e t r a i n i n g . I f t r a i n i n g i s stopped, f o r even a b r i e f p e r i o d of t i m e , a s i g n i f i c a n t r e g r e s s i o n of the i n c r e a s e i n m i t o c h o n d r i a l c o n t e n t can o c c u r ( 5 1 - 5 4 ) . A g a i n , the change i n m i t o c h o n d r i a l c o n t e n t w i l l be n o n - l i n e a r over time. F o r example, i n the f i r s t week ( i . e . , f i r s t h a l f - l i f e ) of d e t r a i n i n g , the e l e v a t e d m i t o c h o n d r i a l c o n t e n t w i l l d e c l i n e a p p r o x i m a t e l y 50% of the way toward the lower n o n - t r a i n e d v a l u e ( F i g u r e 1 ) . F u r t h e r , the second and subsequent weeks of d e t r a i n i n g w i l l p e r m i t a d d i t i o n a l d e c l i n e s i n m i t o c h o n d r i a l c o n t e n t , each r e p r e s e n t i n g o n e - h a l f of the remaini n g f a l l toward the normal p r e t r a i n i n g v a l u e . Thus, because of the f i r s t - o r d e r n a t u r e of p r o t e i n t u r n o v e r , the g r e a t e s t a b s o l u t e change i n the d e t r a i n i n g p r o c e s s o c c u r s i n i t i a l l y . T h i s i n d i c a t e s t h a t the e x e r c i s e program s h o u l d be r o u t i n e l y performed, i f the peak a d a p t i v e response i s t o be m a i n t a i n e d . H i c k s o n (55) has shown t h a t t r a i n i n g induced b i o c h e m i c a l changes i n muscle can be o p t i m i z e d by r u n n i n g almost d a i l y ( i . e . , 6 days/week). T h i s i s c o n s i s t e n t w i t h the need to m a i n t a i n the t r a i n i n g s t i m u l u s operant w i t h i n the muscle cont i n u o u s l y over t i m e . As d i s c u s s e d by Booth ( 5 6 ) , i f a one week p e r i o d of d e t r a i n i n g has o c c u r r e d , a d i s p r o p o r t i o n a l d u r a t i o n of t r a i n i n g would be n e c e s s a r y f o r the m i t o c h o n d r i a l content t o r e c o v e r f u l l y , even i f the f u l l t r a i n i n g s c h e d u l e i s q u i c k l y r e e s t a b l i s h e d (Figure 1). R e c a l l t h a t d u r i n g the a d a p t i v e p r o c e s s each week of t r a i n i n g p e r m i t s o n l y o n e - h a l f of the change p o s s i b l e . Thus, app r o x i m a t e l y 4 weeks would be r e q u i r e d t o permit f u l l r e c o v e r y of the m i t o c h o n d r i a l c o n t e n t . A l t h o u g h t h i s extended p e r i o d of time would be needed t o r e c o v e r from the i n i t i a l d e c l i n e i n m i t o c h o n d r i a l c o n t e n t , the r e c o v e r y of o t h e r t r a i n i n g responses, such as a l t e r e d b l o o d t r i g l y c e r i d e content ( 5 7 ) , may f o l l o w a v e r y d i f f e r e n t time course. T h e r e f o r e , as d i s c u s s e d below, the e x i s t e n c e of r e l a t i v e l y s m a l l d i f f e r e n c e s i n m i t o c h o n d r i a l c o n t e n t may have l i t t l e impact on the r e c o v e r y of e x e r c i s e performance f o l l o w i n g a b r i e f p e r i o d of inactivity.



2.

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E x e r c i s e I n t e n s i t y . The importance of e x e r c i s e i n t e n s i t y was f i r s t apparent when comparing the response induced by swimming v e r s u s t r e a d m i l l r u n n i n g t r a i n i n g programs. Swim t r a i n i n g does not produce as g r e a t an i n c r e a s e i n m i t o c h o n d r i a l c o n t e n t i n animals as found w i t h r u n n i n g ( 1 0 , 5 8 ) . I n f a c t , e a r l y s t u d i e s e v a l u a t i n g an e x e r c i s e response w i t h swim t r a i n i n g f a i l e d t o f i n d a s i g n i f i c a n t b i o c h e m i c a l change i n the h i n d l i r a b muscles ( 5 9 ) . I t i s l i k e l y t h a t the w e i g h t b e a r i n g a c t i v i t y a s s o c i a t e d w i t h t r e a d m i l l r u n n i n g exaggerates the c e l l u a r s t i m u l u s r e q u i r e d t o induce a l a r g e b i o c h e m i c a l response. I n g e n e r a l , the g r e a t e r the e x e r c i s e i n t e n s i t y the g r e a t e r w i l l be the induced response w i t h i n the w o r k i n g muscles (44,60,61). This g e n e r a l i z a t i o n , however, must be tempered by the known o r d e r e d p a t t e r n of muscle f i b e r type r e c r u i t m e n t mentioned above ( 4 4 ) . T h i s becomes e v i d e n t from the d a t a p r e s e n t e d i n F i g u r e 2, showing the i n c r e a s e i n cytochrome c content (an i n d e x of m i t o c h o n d r i a l c o n t e n t ) i n the t h r e e f i b e r types as a f u n c t i o n of i n t e n s i t y of t r e a d m i l l running. T h i s f i g u r e was generated a f t e r f i r s t d e t e r m i n i n g the i n f l u e n c e of i n c r e a s i n g d a i l y d u r a t i o n of e x e r c i s e , f o r t r a i n i n g programs at each r u n n i n g i n t e n s i t y (10, 20, 30, 40, 50, and 60 meters/minute) ( 4 4 ) . The peak response o b t a i n e d f o r each r u n n i n g i n t e n s i t y , w h i c h u s u a l l y corresponded t o an a s y m p t o t i c v a l u e , was then p l o t t e d a g a i n s t e x e r c i s e i n t e n s i t y . This provides a charact e r i z a t i o n of the i n t e n s i t y i n f l u e n c e t h a t i s e s s e n t i a l l y independent of the d u r a t i o n of d a i l y e x e r c i s e ( 4 4 ) . I t i s apparent t h a t the f a s t - t w i t c h red f i b e r s e c t i o n of the v a s t u s l a t e r a l i s and the s l o w - t w i t c h r e d s o l e u s muscles adapt w i t h a n e a r l y l i n e a r i n c r e a s e i n m i t o c h o n d r i a l c o n t e n t over the e a s y - t o moderate range of e x e r c i s e c o n d i t i o n s (10, 20, and 30 m/min). T h i s response emphasizes the importance of e x e r c i s e i n t e n s i t y i n i n d u c i n g the b i o c h e m i c a l change. Indeed, t h e r e i s a r e l a t i v e l y l a r g e adapt i v e change w i t h o n l y s m a l l changes i n e x e r c i s e i n t e n s i t y as r e f l e c t e d i n t r e a d m i l l speed. However, i t i s o b v i o u s t h a t the increase i n m i t o c h o n d r i a l content, that occurs w i t h i n c r e a s i n g t r e a d m i l l speed, i s not l i n e a r . I n the case of the f a s t - t w i t c h r e d muscle s e c t i o n , a maximal response was found w i t h t r a i n i n g a f t e r speeds of a p p r o x i m a t e l y 30 m/min ( F i g u r e 2 ) . T h i s corresponds t o an e s t i m a t e d e x e r c i s e i n t e n s i t y f o r the r a t of a p p r o x i m a t e l y 80 - 85% of i t s maximal oxygen consumption ( 6 2 ) . The b r i e f p r o p o r t i o n a l response phase up t o 30 m/min, t o g e t h e r w i t h the p l a t e a u , c o u l d account f o r the apparent l a c k of an i n t e n s i t y e f f e c t observed i n some s t u d i e s (61 ). A l t h o u g h t h i s p l a t e a u suggests t h a t e x e r c i s e i n t e n s i t y i s no l o n g e r i m p o r t a n t , a more p h y s i o l o g i c a l i n t e r p r e t a t i o n seems a p p r o p r i a t e . I t may be t h a t t h i s f i b e r t y p e was r e c r u i t e d i n an i n c r e a s i n g manner over the lower speeds, but t h a t a s a t u r a t i o n of t h i s motor u n i t p o o l o c c u r r e d at a p p r o x i m a t e l y 30 - 40 m/min. I f t h i s were the case, then t r e a d m i l l r u n n i n g at speeds of 50 and 60 m/min c o u l d not be accomplished w i t h o u t the involvement of a d d i t i o n a l motor u n i t s . These a d d i t i o n a l motor u n i t s may be the f a s t - t w i t c h white f i b e r s . There was no change i n cytochrome c c o n t e n t i n the f a s t - t w i t c h w h i t e s e c t i o n throughout the m i l d t o moderate e x e r c i s e i n t e n s i t y . However, an a d a p t i v e change became apparent i n the f a s t - t w i t c h w h i t e s e c t i o n w i t h i n c r e a s i n g e x e r c i s e i n t e n s i t y above 30 - 40 m/min ( F i g u r e 2 ) . T h i s corresponds t o the


14

NUTRITION A N D AEROBIC EXERCISE


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2 h r / ( J a

F i g u r e 1, The p r e d i c t e d consequences o f one week o f d e t r a i n i n g and t h e time o f r e t r a i n i n g r e q u i r e d t o r e c o v e r the f u l l i n c r e a s e i n cytochrome c content ( a n i n d e x o f m i t o c h o n d r i a l c o n t e n t ) i n the w o r k i n g muscle. Note t h a t i n one week of i n a c t i v i t y (approx. 1 h a l f - l i f e ) , n e a r l y 50% o f t h e t r a i n i n g e f f e c t i s l o s t . Simi l a r l y , each week o f r e t r a i n i n g r e c o v e r s approx, 50% o f t h e way toward t h e f u l l t r a i n i n g e f f e c t . Since the process e x h i b i t s f i r s t - o r d e r k i n e t i c s , i t takes longer t o recover f u l l y . "Repro duced w i t h p e r m i s s i o n from R e f . 56. C o p y r i g h t 1977, New Y o r k Academy of S c i e n c e s . " f

1

30 f 28 26 24 22 20 18 16 14 12 10 8 6 4 2

red vastus

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soleus

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62% 73% 83% 94% 105% H6%maxV0 —I 1 1 1 1 1— 10 20 30 40 50 60 meter/min EXERCISE

2

INTENSITY

F i g u r e 2. The i n f l u e n c e o f e x e r c i s e i n t e n s i t y ( t r e a d m i l l r u n n i n g ) on muscle cytochrome c content i n the r a t . Red v a s t u s = f a s t - t w i t c h r e d f i b e r s e c t i o n ; Soleus - s l o w - t w i t c h r e d f i b e r s e c t i o n ; White v a s t u s = f a s t - t w i t c h w h i t e f i b e r s e c t i o n . "Re produced w i t h p e r m i s s i o n from R e f . 44. C o p y r i g h t 1982, A m e r i c a n Physiological Society ." 1

1



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t r e a d m i l l speeds where the response i n the f a s t - t w i t c h red s e c t i o n reached a p l a t e a u . Thus, the g e n e r a l response t o t r a i n i n g i n t e n s i t y , i l l u s t r a t e d i n F i g u r e 2, i s c o n s i s t e n t w i t h the e x p e c t e d o r d e r e d p a t t e r n of motor u n i t r e c r u i t m e n t . These d a t a a l s o i l l u s t r a t e t h a t care must be e x e r c i s e d when i n t e r p r e t i n g the t r a i n i n g response o b t a i n e d from mixed muscle s e c t i o n s , where each component f i b e r type may be a d a p t i n g i n a q u a n t i t a t i v e l y d i f f e r e n t manner. N o n e t h e l e s s , i t i s c l e a r t h a t the i n t e n s i t y of e x e r c i s e e x e r t s a p r o f o u n d i n f l u e n c e on the magnitude of the b i o c h e m i c a l change. F u r t h e r , t h i s response need not be s i m i l a r f o r a l l f i b e r t y p e s . For example, at the most i n t e n s e t r a i n i n g program of 60 m/min, the cytochrome c content i n the f a s t - t w i t c h w h i t e f i b e r s e c t i o n was 3 . 0 - f o l d normal, but o n l y 1 . 5 - f o l d normal i n the f a s t - t w i t c h r e d muscle s e c t i o n . T h i s q u a n t i t a t i v e d i f f e r e n c e may be e x p e c t e d , i f the s t i m u l u s i n d u c i n g the i n c r e a s e i n o x i d a t i v e c a p a c i t y i s at a l l i n f l u e n c e d by the p r e e x i s t i n g m i t o c h o n d r i a l content w i t h i n the muscle f i b e r . Note t h a t the cytochrome c content i n the f a s t - t w i t c h r e d s e c t i o n i s a p p r o x i m a t e l y 4-times t h a t of the f a s t - t w i t c h w h i t e s e c t i o n (see y - a x i s of F i g u r e 2 ) . Thus, i t i s p r o b a b l e t h a t a g r e a t e r t r a i n i n g s t i m u l u s i s needed to b r i n g about an a d a p t a t i o n i n the well-endowed h i g h - o x i d a t i v e f i b e r s as compared w i t h the lowoxidative fibers. T h i s i s c o n s i s t e n t w i t h the g e n e r a l i m p r e s s i o n concerning t r a i n i n g adaptations. I n d i v i d u a l s who p o s s e s s a r e l a t i v e l y h i g h a e r o b i c work c a p a c i t y must t r a i n " h a r d e r " i n o r d e r t o a c h i e v e a s i g n i f i c a n t a d a p t i v e change ( 6 3 ) . E x e r c i s e Bout D u r a t i o n . The g e n e r a l e x p e c t a t i o n t h a t t r a i n i n g programs which r e q u i r e l o n g e r d a i l y e x e r c i s e bouts produce g r e a t e r a d a p t a t i o n s has been found f o r the b i o c h e m i c a l changes i n muscle (44,60,64). A l t h o u g h l e n g t h e n i n g e x e r c i s e bout d u r a t i o n appears to induce a f a i r l y l i n e a r i n c r e a s e i n m i t o c h o n d r i a l content (44,60,64), t h e r e i s p r o b a b l y a f i n i t e range f o r t h i s r e l a t i o n s h i p . When e x e r c i s e d u r a t i o n was v e r y p r o l o n g e d ( i . e . , 4 h r / d a y ) , the a d a p t i v e change was not d i f f e r e n t from t h a t found when d a i l y e x e r c i s e i n v o l v e d r u n n i n g 2 hr/day ( 6 0 ) . Thus, t h e r e i s an e x e r c i s e bout d u r a t i o n w h i c h , when exceeded, does not produce any added i n c r e a s e i n mitochondrial content. F u r t h e r , i t i s p r o b a b l e t h a t the r e l a t i o n s h i p between the b i o c h e m i c a l a d a p t a t i o n i n muscle and e x e r c i s e bout d u r a t i o n can be d e s c r i b e d as a f i r s t o r d e r p r o c e s s where the i n f l u e n c e of time i s not c o n s t a n t ( 4 4 ) . This i s i l l u s t r a t e d i n F i g u r e 3 f o r the i n c r e a s e i n cytochrome c content i n the f a s t - t w i t c h w h i t e muscle s e c t i o n of t r a i n e d r a t s . This r e l a t i o n s h i p indicates t h a t , d u r i n g steady s t a t e t r a i n i n g , the i n i t i a l minutes of the e x e r c i s e bout are the most important i n c r e a t i n g the c e l l u l a r s t i m u l u s t h a t induces the b i o c h e m i c a l change. The f u r t h e r i n c r e a s e i n t h i s c e l l u l a r s t i m u l u s d i m i n i s h e s as the d u r a t i o n of each e x e r c i s e bout i n c r e a s e s , u n t i l an e x e r c i s e bout d u r a t i o n i s reached where added time has l i t t l e i f any impact. A l t h o u g h l i t t l e i s known about the exact s i g n a l w i t h i n the c e l l t h a t produces the i n c r e a s e i n m i t o c h o n d r i a l c o n t e n t , i t may be i n some way i n f l u e n c e d by the e x i s t i n g o x i d a t i v e c a p a c i t y of the muscle f i b e r . F o r example, the d e c r e a s i n g importance of e x e r c i s e bout d u r a t i o n c o u l d be e x p l a i n e d i f the magnitude of the c e l l u l a r s t i m u l u s were m o d i f i e d by the a d a p t i v e response i t s e l f . Thus, the t h i r d 15 minute p e r i o d of e x e r c i s e would be e x p e c t e d t o induce a s m a l l e r e f f e c t than the f i r s t


16



15 minute p e r i o d of e x e r c i s e , s i n c e t h e r e a l r e a d y e x i s t s a s i g n i f i cant a d a p t i v e response caused by the i n i t i a l e x e r c i s e time p e r i o d . A n o t h e r example may be the exaggerated i n c r e a s e i n m i t o c h o n d r i a l content i n the low o x i d a t i v e f a s t - t w i t c h w h i t e s e c t i o n , as compared to the h i g h o x i d a t i v e f a s t - t w i t c h r e d s e c t i o n , d u r i n g i n t e n s e e x e r c i s e t r a i n i n g . However, u n l i k e a s i m p l e change i n e x e r c i s e bout d u r a t i o n , i t i s not known whether the u t i l i z a t i o n of each muscle type was the same d u r i n g the i n t e n s e e x e r c i s e bouts. I n t e r a c t i o n Between E x e r c i s e D u r a t i o n and I n t e n s i t y . Although e x e r c i s e bout d u r a t i o n and i n t e n s i t y a r e d i s t i n c t t r a i n i n g p a r a m e t e r s , they a l s o i n t e r a c t t o f u r t h e r a l t e r the a d a p t i v e r e s p o n s e . T h i s becomes apparent when n o t i n g the time n e c e s s a r y t o a c h i e v e the maximal a d a p t i v e change f o r each of the r u n n i n g i n t e n s i t i e s . This i s b e s t i l l u s t r a t e d by the response i n the f a s t - t w i t c h w h i t e muscle ( F i g u r e 3 ) . The g r e a t e r the i n t e n s i t y of e x e r c i s e , the more r a p i d y the change i n cytochrome c content approaches i t s peak a s y m p t o t i c r e s p o n s e . Thus, i t i s p o s s i b l e to a c h i e v e the same a d a p t i v e change w i t h i n muscle r u n n i n g f o r a s h o r t e r time/day, i f the i n t e n s i t y of exercise i s increased accordingly. The f a c t o r ( s ) t h a t change(s) w i t h i n the muscle c e l l e n a b l i n g the i n i t i a l minutes of e x e r c i s e t o produce a g r e a t e r t r a i n i n g s t i m u l u s i s not known. However, the e x a g g e r a t e d m e t a b o l i c response t h a t o c c u r s w i t h i n muscle as e x e r c i s e i n t e n s i t y i s i n c r e a s e d may be i m p l i c a t e d . Thus, e x e r c i s e i n t e n s i t y a f f e c t s b o t h the magnitude of the a d a p t i v e response, as w e l l as the e x e r c i s e bout time n e c e s s a r y t o a c h i e v e the peak response. F u n c t i o n a l S i g n i f i c a n c e of T r a i n i n g A d a p t a t i o n s

i n Muscle

The i n c r e a s e i n m i t o c h o n d r i a l content w i t h i n t r a i n e d muscle c o u l d have s e v e r a l s i g n i f i c a n t f u n c t i o n a l i n f l u e n c e s d u r i n g e x e r c i s e . F i r s t , t h e g r e a t e r b i o c h e m i c a l c a p a c i t y f o r ATP p r o v i s i o n v i a a e r o b i c metabolism c o u l d g r e a t l y i n c r e a s e the maximal oxygen consumption of muscle. T h i s would be t r u e i f a) muscle c o u l d u t i l i z e a g r e a t e r ATP t u r n o v e r than e v i d e n t at maximal a e r o b i c work c a p a c i t y p r i o r t o t r a i n i n g , and b) the g r e a t e r m i t o c h o n d r i a l content was s u p p l i e d w i t h s u f f i c i e n t oxygen to support the g r e a t e r ATP t u r n o v e r . S i n c e muscle e x h i b i t s a d e p l e t i o n of p h o s p h o c r e a t i n e (PCr) and, a t t i m e s , a r e d u c t i o n i n ATP content d u r i n g severe c o n t r a c t i o n c o n d i t i o n s (37,39,65,66), i t i s p r o b a b l e t h a t a h i g h e r energy u t i l i z a t i o n c o u l d h a v e o c c u r r e d i f more e n e r g y were a v a i l a b l e t o meet t h e demand. Thus, the p o t e n t i a l t h a t an i n c r e a s e d m i t o c h o n d r i a l c o n t e n t might i n c r e a s e the maximal oxygen consumption of muscle p r o b a b l y r e s t s on the a v a i l a b i l i t y of oxygen. An i n c r e a s e d s u p p l y of oxygen to m i t o c h o n d r i a of c o n t r a c t i n g muscle would occur i f a) t h e r e was an i n c r e a s e d e x t r a c t i o n of oxygen from the a r t e r i a l b l o o d f l o w i n g t h r o u g h the muscle, and/or b) t h e r e was a g r e a t e r b l o o d f l o w t h r o u g h the muscle ( a r t e r i a l b l o o d oxygen content remains remarkably cons t a n t d u r i n g a l l i n t e n s i t i e s of e x e r c i s e ( 6 7 ) . Oxygen e x t r a c t i o n a c r o s s w o r k i n g muscle d u r i n g maximal e x e r c i s e i s g e n e r a l l y v e r y l a r g e ( a p p r o x i m a t e l y 80% or more), even i n u n t r a i n e d i n d i v i d u a l s (67 ). A s m a l l i n c r e a s e i n oxygen e x t r a c t i o n ( a p p r o x i m a t e l y 10-15%) a c r o s s w o r k i n g muscle a f t e r t r a i n i n g has been observed (63,68), but not c o n s i s t e n t l y ( 2 5 , 6 9 ) . Thus, an i n c r e a s e i n oxygen s u p p l y due t o a g r e a t e r e x t r a c t i o n c o u l d not p o s s i b l y support a l l of the l a r g e



TERJUNG AND HOOD

Biochemical

30 RUN

TIME

Adaptations

60

in Skeletal

Muscle

90

(MINUTES/DAY)

F i g u r e 3· The i n f l u e n c e o f e x e r c i s e d u r a t i o n , d u r i n g d i f f e r e n t i n t e n s i t i e s of t r e a d m i l l r u n n i n g , on cytochrome c content i n t h e w h i t e s e c t i o n of t h e v a s t u s l a t e r a l i s muscle ( f a s t - t w i t c h w h i t e f i b e r s ) of r a t s . Running speed: ( Ο ) 10 m/min, ( • ) 20 m/min, ( Δ ) 30 m/min, ( · ) 40 m/min, ( • ) 50 m/min, ( • ) 60 m/min. "Reproduced w i t h p e r m i s s i o n from R e f . 44. C o p y r i g h t 1982, American Physiological Society'."



18

NUTRITION A N D

AEROBIC EXERCISE

i n c r e a s e i n m i t o c h o n d r i a l content ( e . g . , 100%) t y p i c a l l y found w i t h endurance t r a i n i n g . T h i s i n d i c a t e s t h a t b l o o d f l o w must be i n c r e a s e d i f the g r e a t e r c a p a c i t y f o r o x i d a t i v e metabolism w i t h i n the t r a i n e d muscle i s to be u t i l i z e d m a x i m a l l y . Measurements e v a l u a t i n g the p o t e n t i a l f o r changes i n peak b l o o d f l o w d u r i n g maximal e x e r c i s e h a v e p r o v i d e d e q u i v o c a l r e s u l t s ( 7_0 ) . Thus, t h e r e i s l i t t l e a s s u r a n c e t h a t t r a i n i n g g r e a t l y a l t e r s maximal b l o o d f l o w . Recent evidence, obtained i n t r a i n e d r a t s using r a d i o l a b e l e d microspheres, has demonstrated a s i g n i f i c a n t i n c r e a s e i n peak muscle b l o o d f l o w i n muscle of t r a i n e d r a t s (71 ). However, the i n c r e a s e of a p p r o x i m a t e l y 40 - 50% was found o n l y i n the low o x i d a t i v e f a s t - t w i t c h w h i t e muscle f i b e r s e c t i o n . A l t h o u g h t h i s appears t o be a s i g n i f i c a n t change, i t s o v e r a l l c o n t r i b u t i o n to an i n c r e a s e i n t o t a l body oxygen consumption of the animal would be r a t h e r s m a l l . T h i s low mitochond r i a l f i b e r s e c t i o n r e c e i v e s o n l y a p p r o x i m a t e l y 20 - 25% of the b l o o d f l o w d e l i v e r e d t o the h i g h o x i d a t i v e f a s t - t w i t c h r e d s e c t i o n (32,33). T h e r e f o r e , the r e d muscle f i b e r types p r o b a b l y account f o r at l e a s t 80% of the maximal oxygen consumption of the r a t ( 3 3 ) . T h i s r e l i g a t e s any change i n peak b l o o d f l o w t o the f a s t - t w i t c h w h i t e s e c t i o n due t o t r a i n i n g as e x e r t i n g a r e l a t i v e l y m i n o r i n f l u e n c e on t o t a l body maximal oxygen consumption. Similarly, in humans, t r a i n i n g induces a change i n maximal oxygen consumption t h a t i s r e l a t i v e l y s m a l l ( e . g . , t y p i c a l l y 15 - 2 5 % ) , compared t o the i n c r e a s e i n m i t o c h o n d r i a l content induced i n the w o r k i n g muscle (e.g., 54). Thus, i t i s g e n e r a l l y r e c o g n i z e d t h a t the f u l l potent i a l of the enhanced o x i d a t i v e c a p a c i t y i s not f u l l y r e a l i z e d . D a v i e s , et a l (72) r e c e n t l y r e p o r t e d i n t e r e s t i n g d a t a w h i c h i l l u s t r a t e the r e l a t i o n s h i p between oxygen t r a n s p o r t c a p a c i t y and maximal oxygen consumption d u r i n g e x e r c i s e . They found, as exp e c t e d , t h a t r e d u c i n g the oxygen t r a n s p o r t c a p a c i t y by d e c r e a s i n g hemoglobin c o n c e n t r a t i o n w i t h an i r o n d e f i c i e n t d i e t , g r e a t l y d e c r e a s e d the maximal oxygen consumption d u r i n g e x e r c i s e i n r a t s . D u r i n g the subsequent i r o n r e f e e d i n g p e r i o d , the time course of the r e t u r n of maximal oxygen consumption n i c e l y corresponded t o the time course of the r e c o v e r y of oxygen t r a n s p o r t c a p a c i t y ( i . e . , hemoglobin content). F u r t h e r , when the oxygen t r a n s p o r t c a p a c i t y of i r o n d e f i c i e n t r a t s was r e t u r n e d t o normal by i n f u s i o n of packed red b l o o d c e l l s , the maximal oxygen consumption d u r i n g e x e r c i s e essent i a l l y recovered to normal ( 7 3 ) . These r e s u l t s i l l u s t r a t e the g e n e r a l f i n d i n g t h a t maximal a e r o b i c work c a p a c i t y i s c l o s e l y r e l a t e d t o maximal c a r d i o v a s c u l a r t r a n s p o r t of o x y g e n . ( 7 4 ) . Theref o r e , the f u n c t i o n a l s i g n i f i c a n c e of the a d a p t i v e i n c r e a s e i n m i t o c h o n d r i a l content may be r e l a t e d to c e l l u l a r responses w i t h i n the w o r k i n g muscle d u r i n g submaximal e x e r c i s e . Oxygen t r a n s p o r t i s d i s c u s s e d i n more d e t a i l i n the T r a c e Element c h a p t e r by McDonald and Saltman. C e l l u l a r Responses i n T r a i n e d M u s c l e . Recent e v i d e n c e , obtained from a p p r o p r i a t e measurements of m e t a b o l i t e s w i t h i n the c e l l d u r i n g c o n t r a c t i o n s , suggests t h a t s k e l e t a l muscle of t r a i n e d i n d i v i d u a l s i s b e t t e r a b l e t o a d j u s t , as compared t o s k e l e t a l muscle of unt r a i n e d i n d i v i d u a l s , t o the energy demands of a submaximal c o n t r a c t i o n e f f o r t . T h i s i s apparent s i n c e m e t a b o l i c c o n d i t i o n s a l t e r e d by c o n t r a c t i o n s w i t h i n t r a i n e d muscle change l e s s than i n u n t r a i n e d muscle from t h a t found at r e s t . F o r example, the PCr content of



2.

TERJUNG AND HOOD

Biochemical

Adaptations

in Skeletal

Muscle

19

muscle decreases I n p r o p o r t i o n t o e x e r c i s e i n t e n s i t y throughout the submaximal range of e x e r c i s e (66,75). D u r i n g moderately i n t e n s e c o n t r a c t i o n c o n d i t i o n s , the decrease i n PCr content t o t r a i n e d muscle of r a t s i s l e s s than t h a t of u n t r a i n e d muscle ( 4 0 ) . Simil a r l y , the decrease i n PCr content d u r i n g submaximal c y c l e e x e r c i s e (150 w a t t s ) i n humans was l e s s a f t e r p h y s i c a l t r a i n i n g ( 7 6 ) . Thus, a g r e a t e r work output ( i . e . , energy t u r n o v e r ) can be a c h i e v e d a f t e r t r a i n i n g f o r the same decrease i n PCr c o n c e n t r a t i o n . The decrease i n PCr, t h r o u g h the c e l l ' s c o r r e s p o n d i n g i n c r e a s e i n i n o r g a n i c phosphate c o n c e n t r a t i o n ( 7 7 ) , i s thought t o c o n t r i b u t e to the c e l l u l a r s i g n a l t h a t s t i m u l a t e s the m i t o c h o n d r i a t o i n c r e a s e r e s p i r a t i o n (78,79). T h i s c o u l d be p a r t o f t h e r e s p o n s e t h a t accounts f o r the t i g h t c o u p l i n g between m i t o c h o n d r i a l ATP p r o d u c t i o n (and, t h e r e f o r e , oxygen consumption) and the g r e a t e r energy demands as e x e r c i s e i n t e n s i t y i n c r e a s e s . I f the decrease i n PCr c o n t r i b u t e s to the c e l l u l a r s i g n a l t o a c c e l e r a t e m i t o c h o n d r i a l respiration (78,79), then a h i g h e r r a t e of oxygen consumption seems t o o c c u r a t a r e l a t i v e l y smaller i n t r a c e l l u l a r signal driving mitochondrial respiration. T h i s i s r e a s o n a b l e s i n c e t h e r e are more m i t o c h o n d r i a w i t h i n the t r a i n e d muscle f i b e r t o respond and r e p h o s p h o r y l a t e ADP to ATP ( 5 , 2 3 ) . Thus, t r a i n e d muscle seems t o be a b l e t o f u n c t i o n a t a g i v e n oxygen consumption (work r a t e ) w i t h a s m a l l e r m e t a b o l i c signal driving mitochondrial respiration; alternatively, trained muscle can f u n c t i o n at a h i g h e r oxygen consumption ( i . e . , work r a t e ) a t the same apparent c e l l u l a r s t i m u l u s as found i n u n t r a i n e d muscle w o r k i n g at a lower oxygen consumption. Thus, i t i s p r o b a b l e t h a t the t r a i n i n g induced change i n m i t o c h o n d r i a l content a l t e r s metab o l i c c o n t r o l parameters. Another i n f l u e n c e of the t r a i n i n g a d a p t a t i o n may be d u r i n g the t r a n s i t i o n from r e s t i n g metabolism t o the a c c e l e r a t e d r a t e of r e s p i r a t i o n r e q u i r e d by c o n t r a c t i o n s . F o r example, a h i g h e r mitochond r i a l d e n s i t y w i t h i n t r a i n e d muscle might e f f e c t a more r a p i d t r a n s i t i o n toward a steady s t a t e a e r o b i c energy p r o v i s i o n at the onset of c o n t r a c t i o n s . I f the energy demands were being b e t t e r met by m i t o c h o n d r i a l r e s p i r a t i o n , then the r a t e of a n a e r o b i c energy p r o d u c t i o n c o u l d be l e s s . That t h i s o c c u r s i s suggested by the c e l l u l a r content of l a c t i c a c i d t h a t d e v e l o p s at the onset of cont r a c t i o n s (40). L a c t a t e content i n c r e a s e d t o 13.2+1.31 pmole/g i n f a s t - t w i t c h red muscle of s e d e n t a r y animals compared t o o n l y 7.1+0.84 i n t r a i n e d muscle d u r i n g the f i r s t minute of c o n t r a c t i o n s (40). These r e s u l t s are t y p i c a l (25,76,80) and c o u l d r e p r e s e n t the f a v o r e d m e t a b o l i c s i t u a t i o n i n t r a i n e d muscle t h a t c o n t r i b u t e s t o a more r a p i d achievement of steady s t a t e oxygen consumption (81,82,83) and a reduced c i r c u l a t i n g l a c t a t e content (76,80) observed a f t e r exercise training. A l t e r e d S u b s t r a t e U t i l i z a t i o n by T r a i n e d M u s c l e . I t i s l i k e l y t h a t the g r e a t e r m i t o c h o n d r i a l content a l s o s e r v e s t o a l t e r the energy s u b s t r a t e u t i l i z e d d u r i n g prolonged submaximal e x e r c i s e . This probably c o n t r i b u t e s to the much enhanced endurance performance t y p i c a l of the endurance t r a i n e d i n d i v i d u a l . I t has l o n g been r e c o g n i z e d t h a t t r a i n e d i n d i v i d u a l s o b t a i n a g r e a t e r f r a c t i o n of t h e i r energy needs from the o x i d a t i o n of f a t t y a c i d s than u n t r a i n e d i n d i v i d u a l s e x e r c i s i n g at the same work i n t e n s i t y ( c f . 6 ) . The g r e a t e r e x t e n t of l i p i d o x i d a t i o n , e v i d e n t by a lower r e s p i r a t o r y


20


q u o t i e n t o f t r a i n e d i n d i v i d u a l s , h a s b e e n c o n f i r m e d by d i r e c t measurements of enhanced C02 p r o d u c t i o n from i n f u s e d l a b e l e d p a l m i t a t e (84)« A l t h o u g h an enhanced c o n c e n t r a t i o n o f c i r c u l a t i n g f a t t y a c i d s can i n c r e a s e f a t o x i d a t i o n and extend e x e r c i s e time ( 8 5 , 8 6 ) , the i n c r e a s e d l i p i d o x i d a t i o n i n t r a i n e d i n d i v i d u a l s i s apparent even when c i r c u l a t i n g f a t t y a c i d l e v e l s a r e not d i f f e r e n t from t h a t o f the n o n - t r a i n e d ( 8 7 ) . Thus, t h e r e i s p r o b a b l y some fundamental a l t e r a t i o n w i t h i n t h e w o r k i n g muscle t o p e r m i t t h e g r e a t e r r a t e of b e t a o x i d a t i o n . R e c a l l t h a t an i n c r e a s e i n t h e capacity f o r f a t t y acid oxidation i s included i n the adaptive response of a g r e a t e r m i t o c h o n d r i a l c o n t e n t ( 1 5 ) . A g r e a t e r enzyme c o n t e n t w i t h i n t h e muscle c o u l d r e s u l t i n a g r e a t e r r a t e o f f a t t y a c i d o x i d a t i o n , even when t h e same f a t t y a c i d c o n c e n t r a t i o n i s a v a i l a b l e f o r b e t a o x i d a t i o n (15). One d i r e c t c o n s e q u e n c e o f o b t a i n i n g a g r e a t e r f r a c t i o n of the energy from f a t t y a c i d d e r i v e d a c e t y l C o A i s t o l e s s e n the demand f o r o t h e r carbon s o u r c e s f o r o x i d a t i o n . T h i s would be expected t o reduce t h e r a t e of g l y c o l y s i s and p o t e n t i a l l y t h e r a t e of g l y c o g e n u t i l i z a t i o n i n the w o r k i n g muscle. Recent e v i d e n c e i n d i c a t e s t h a t enhancing f a t t y acid o x i d a t i o n does, i n d e e d , spare muscle g l y c o g e n (85,86,88). These metabolic changes a r e d i s c u s s e d i n more d e t a i l i n t h e f o l l o w i n g c h a p t e r by Goodman. S i n c e t h e d e p l e t i o n of muscle g l y c o g e n s t o r e s d u r i n g p r o l o n g e d submaximal e x e r c i s e c o r r e s p o n d s w i t h exhaustion, t h e r e i s now r e a s o n t o c o u p l e t h e t r a i n i n g a d a p t a t i o n o f an i n c r e a s e d m i t o c h o n d r i a l c o n t e n t w i t h i n t h e w o r k i n g muscle t o t h e marked i n c r e a s e i n endurance performance. S p e c i f i c a l l y , t h e g r e a t e r m i t o c h o n d r i a l content p e r m i t s an enhanced energy s u p p l y from l i p i d o x i d a t i o n ; t h i s , i n t u r n , r e t a r d s t h e r a t e o f u t i l i z a t i o n o f muscle g l y c o g e n , thereby p e r m i t t i n g muscle g l y c o g e n t o be used over an extended exercise time. A l t h o u g h many o t h e r p h y s i o l o g i c a l , m e t a b o l i c and e n d o c r i n e changes must be i m p o r t a n t i n the t r a i n i n g p r o c e s s , b i o c h e m i c a l a d a p t a t i o n s w i t h i n t h e w o r k i n g muscles appear t o e x e r t a s i g n i f i c a n t i n f l u e n c e on energy metabolism and muscle performance.


1I+

Summary R o u t i n e l y performed p h y s i c a l a c t i v i t y , such as c y c l i n g o r r u n n i n g , i n c r e a s e s one's endurance c a p a c i t y f o r p r o l o n g e d submaximal work. A s s o c i a t e d w i t h t h i s response a r e b i o c h e m i c a l changes w i t h i n t h e w o r k i n g m u s c l e s . T h i s i n c l u d e s an i n c r e a s e i n the c o n t e n t of m i t o c h o n d r i a , the c e l l u l a r o r g a n e l l e where energy (ATP) i s produced by the o x i d a t i o n of f u e l s ( g l u c o s e and f a t ) i n the presence o f oxygen. The magnitude o f t h i s i n c r e a s e i n m i t o c h o n d r i a l c o n t e n t i s i n f l u enced, i n a complex manner, by t h e i n t e n s i t y and d u r a t i o n of e x e r c i s e , s i n c e not a l l s k e l e t a l muscle f i b e r s may be r e c r u i t e d and t h e r e a r e marked d i f f e r e n c e s between muscle f i b e r t y p e s . Most mammalian muscle i s composed of t h r e e d i f f e r e n t f i b e r t y p e s : 1) s l o w - t w i t c h r e d (Type I ) w h i c h i s r e l a t i v e l y slow c o n t r a c t i n g and has a h i g h m i t o c h o n d r i a l c o n t e n t and endurance c a p a c i t y , 2) f a s t t w i t c h r e d (Type l i a ) w h i c h i s r e l a t i v e l y f a s t c o n t r a c t i n g and has a high mitochondrial c o n t e n t and endurance c a p a c i t y , and 3) f a s t t w i t c h w h i t e (Type l i b ) which i s r e l a t i v e l y f a s t c o n t r a c t i n g and has a low m i t o c h o n d r i a l content and endurance c a p a c i t y . These f i b e r types a r e r e c r u i t e d p r o g r e s s i v e l y b e g i n n i n g w i t h Type I , then Type



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Adaptations

in Skeletal

Muscle

21

l i a and f i n a l l y Type l i b as t h e I n t e n s i t y o f e x e r c i s e i n c r e a s e s . Thus, r e g u l a r p h y s i c a l a c t i v i t y o f moderate i n t e n s i t y w i l l i n c r e a s e the m i t o c h o n d r i a l content o f p r i m a r i l y Type I and Type l i a f i b e r s , w h i l e p r o p o r t i o n a l l y l a r g e r i n c r e a s e s are induced i n Type l i b f i b e r s d u r i n g more i n t e n s e p h y s i c a l t r a i n i n g when these f i b e r s a r e r e cruited. One major b e n e f i t o f enhancing the m i t o c h o n d r i a l content i n the w o r k i n g muscles i s r e l a t e d t o the much g r e a t e r c a p a c i t y o f the muscle t o o x i d i z e f a t f o r energy. A g r e a t e r s u p p l y o f energy from f a t s e r v e s t o preserve the intramuscular glucose store ( g l y c o g e n ) w h i c h i s i n l i m i t e d s u p p l y . D e p l e t i o n o f muscle g l y c o g e n has been i m p l i c a t e d as a f a c t o r c a u s i n g f a t i g u e d u r i n g p r o l o n g e d m o d e r a t e l y i n t e n s e e x e r c i s e ( e . g . , r u n n i n g f o r more than 1 h r ) . Thus, the enhanced m i t o c h o n d r i a l content and i t s r e l a t e d i n c r e a s e i n f a t o x i d a t i o n p r o b a b l y c o n t r i b u t e t o the g r e a t l y improved endurance performance f o l l o w i n g e x e r c i s e t r a i n i n g . Acknowledgments C i t e d work by t h e a u t h o r s was supported by N a t i o n a l I n s t i t u t e s o f H e a l t h Grant AM-21617 and R e s e a r c h C a r e e r Development Award AM-00681 ( t o R.L.T.).

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Biochemical Adaptations in Skeletal Muscle Induced by Exercise

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