2 Glycolysis, Gluconeogenesis, 2014

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Text of 2 Glycolysis, Gluconeogenesis, 2014

  • N y i M e k a r S a p t a r i n i1

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  • 1. Preparatory phase : Phosphorylation of glucose and its conversion to glyceraldehyde3-phosphate

    2. Payoff phase : Oxidative conversion of glyceraldehyde 3-phosphate to pyruvate and glyceraldehyde 3-phosphate to pyruvate and the coupled formation of ATP and NADH.

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  • (1) degradation of the carbon skeleton of glucose to yield pyruvate,

    (2) phosphorylation of ADP to ATP by high-energy phosphate compounds formed during glycolysis, energy phosphate compounds formed during glycolysis,

    (3) transfer of a hydride ion to NAD, forming NADH.

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  • Plasma membrane lacks transporters for phosphorylated sugars, the intermediates cannot leave the cell.

    Phosphoryl groups are essential components in the enzymatic conservation of metabolic energy.

    Binding energy resulting from the binding of phosphate groups to the active sites of enzymes lowers the activation energy and the active sites of enzymes lowers the activation energy and increases the specificity of the enzymatic reactions.

    1,3-bisphosphoglycerate & phosphoenolpyruvate donate phosphoryl groups to ADP to form ATP.

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  • Pyruvate is oxidized, with loss of its carboxyl group as CO2, to yield the acetyl group of acetyl-coenzyme A; the acetyl group is then oxidized completely to CO2 by the citric acid cycle .

    Pyruvate is reduced to lactate via lactic acid fermentation in hypoxia, pyruvate accepting electrons from NADH and thereby regenerating the NAD necessary for glycolysis to continue.

    Pyruvate catabolism leads to ethanol via ethanol (alcohol) fermentation under hypoxic or anaerobic (alcohol) fermentation under hypoxic or anaerobic conditions into ethanol and CO2.

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  • H y p o x i a i n a c t i v e s k e l e t a l m u s c l e , i n s u b m e r g e d p l a n t t i s s u e s , o r i n l a c t i c a c i d b a c t e r i a r e g e n e r a t e b a c t e r i a r e g e n e r a t e N A D d u r i n g a n a e r o b i c g l y c o l y s i s b y t r a n s f e r r i n g e l e c t r o n s f r o m N A D H t o f o r m a r e d u c e d e n d p r o d u c t s u c h a s l a c t a t e o r e t h a n o l .

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  • A n a e r o b i c c o n d i t i o n i n a n im a l t i s s u e s :

    p y r u v a t e a n d N A D H p r o d u c e d in g l y c o l y s i s , N A D i s r e g e n e r a t e d f r o m N A D H b y t h e r e d u c t i o n o f p y r u v a t e t o l a c t a t e .

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  • T h e la c t a t e c a n b e r e c y c l e d ; i t i s c a r r i e d i n t h e b l o o d t o t h e l i v e r , w h e r e i t i s c o n v e r t e d t o g l u c o s e d u r i n g t h e r e c o v e r y f r o m s t r e n u o u s t h e r e c o v e r y f r o m s t r e n u o u s m u s c u l a r a c t i v i t y .

    L a r g e q u a n t i t i e s o f l a c t a t e i o n i z a t i o n o f l a c t i c a c i d a c i d i f i c a t i o n i n m u s c l e a n d b l o o d l im i t s t h e p e r i o d o f v i g o r o u s a c t i v i t y .

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  • A n a e r o b i c c o n d i t i o n i n m i c r o o r g a n i s m s :

    G lu c o s e i s c o n v e r t e d t o p y r u v a t eb y g l y c o l y s i s , a n d t h e p y r u v a t ei s c o n v e r t e d t o e t h a n o l a n d C O 2

    1 6

  • A l c o h o l d e h y d r o g e n a s e i s

    p r e s e n t i n m a n y o r g a n i s m s

    t h a t m e t a b o l i z e e t h a n o l ,

    i n c l u d i n g h u m a n s .

    I n h u m a n l i v e r i t c a t a l y z e s

    in c l u d i n g h u m a n s .

    I n h u m a n l i v e r i t c a t a l y z e s

    t h e o x i d a t i o n o f e t h a n o l ,

    e i t h e r i n g e s t e d o r p r o d u c e d

    b y in t e s t i n a l m i c r o o r g a n i s m s ,

    w i t h t h e c o n c o m i t a n t

    r e d u c t i o n o f N A D t o N A D H .

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  • G l u c o n e o g e n e s i s : f o r m a t i o n o f n e w s u g a r c o n v e r t s p y r u v a t ea n d r e l a t e d t h r e e - a n d f o u r -c a r b o n c o m p o u n d s t o g l u c o s e .

    G lu c o n e o g e n e s i s o c c u r w h e n t h e s u p p l y o f g l u c o s e f r o m g l y c o g e n in m u s c l e a n d l i v e r i s t h e s u p p l y o f g l u c o s e f r o m g l y c o g e n in m u s c l e a n d l i v e r i s n o t s u f f i c i e n t : b e t w e e n m e a l s a n d d u r i n g l o n g e r f a s t s , o r a f t e r v i g o r o u s e x e r c i s e .

    O r g a n i s m s s y n t h e s e d g l u c o s e f r o m n o n c a r b o h y d r a t ep r e c u r s o r s .

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  • I n m a m m a l s , g l u c o n e o g e n e s i st a k e s p l a c e in t h e l i v e r a n d t h e r e n a l c o r t e x .

    T h e g l u c o s e p r o d u c e d p a s s e s in t o t h e b l o o d t o s u p p l y o t h e r t i s s u e s . A f t e r v i g o r o u s e x e r c i s e , t i s s u e s . A f t e r v i g o r o u s e x e r c i s e , l a c t a t e p r o d u c e d in s k e l e t a l m u s c l e r e t u r n s t o t h e l i v e r a n d i s c o n v e r t e d t o g l u c o s e , w h i c h m o v e s b a c k t o m u s c l e a n d i s c o n v e r t e d t o g l y c o g e n t h e C o r i c y c l e

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  • 3 r e a c t i o n s o f g l y c o l y s i s a r e i r r e v e r s i b l e a n d c a n n o t b e u s e d in g l u c o n e o g e n e s i s :

    1 . t h e c o n v e r s i o n o f g l u c o s e t o g l u c o s e 6 - p h o s p h a t e b y h e x o k i n a s e , g l u c o s e 6 - p h o s p h a t e b y h e x o k i n a s e ,

    2 . t h e p h o s p h o r y l a t i o n o f f r u c t o s e 6 - p h o s p h a t e t o f r u c t o s e 1 , 6 - b i s p h o s p h a t e b y p h o s p h o f r u c t o k i n a s e - 1 ,

    3 . t h e c o n v e r s i o n o f p h o s p h o e n o l p y r u v a t e t o p y r u v a t e b y p y r u v a t e k i n a s e

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  • T h e s y n t h e s i s o f g l u c o s e f r o m

    p y r u v a t e i s a n e x p e n s i v e p r o c e s s .

    H ig h e n e r g y c o s t i s n e c e s s a r y t o

    e n s u r e t h e i r r e v e r s i b i l i t y o f

    g l u c o n e o g e n e s i s .

    G g l y c o l y s i s i s - 6 3 k J / m o l .

    G g l u c o n e o g e n e s i s i s - 1 6 k J / m o l .

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  • T h e b i o s y n t h e t i c p a t h w a y t o g l u c o s e n o t o n l y f r o m p y r u v a t e , b u t a l s o f r o m t h e f o u r - , f i v e - , a n d s i x - c a r b o n in t e r m e d i a t e s o f t h e c i t r i c a c i d c y c l e .a n d s i x - c a r b o n in t e r m e d i a t e s o f t h e c i t r i c a c i d c y c l e .

    C i t r a t e , i s o c i t r a t e , - k e t o g l u t a r a t e , s u c c i n y l - C o A , s u c c i n a t e , f u m a r a t e , a n d m a l a t e c i t r i c a c i d c y c l e i n t e r m e d i a t e s c a n u n d e r g o o x i d a t i o n t o o x a l o a c e t a t e .

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  • T h e c a r b o n a t o m s o f a m i n o

    a c i d s a r e c a t a b o l i z e d t o

    p y r u v a t e o r t o

    i n t e r m e d i a t e s o f t h e c i t r i c i n t e r m e d i a t e s o f t h e c i t r i c

    a c i d c y c l e .

    S u c h a m i n o a c i d s c a n

    c o n v e r s i o n t o g l u c o s e a n d

    a r e s a i d t o b e g l u c o g e n i c

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  • 3 2

  • T h e m a j o r c a t a b o l i c f a t e o f

    g l u c o s e 6 - p h o s p h a t e i s

    g l y c o l y t i c b r e a k d o w n t o

    p y r u v a t e , t h e n o x i d i z e d v i a t h e

    c i t r i c a c i d c y c l e t o t h e

    f o r m a t i o n o f A T P .

    G lu c o s e 6 - p h o s p h a t e h a s

    o t h e r c a t a b o l i c f a t e s , l e a d t o

    G l u c o s e 6 - p h o s p h a t e h a s

    o t h e r c a t a b o l i c f a t e s , l e a d t o

    s p e c i a l i z e d p r o d u c t s n e e d e d b y

    t h e c e l l .

    S o m e t i s s u e s o x i d a t e d g l u c o s e

    6 - p h o s p h a t e t o p e n t o s e

    p h o s p h a t e s b y t h e p e n t o s e

    p h o s p h a t e p a t h w a y .

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  • R a p i d l y d i v i d i n g c e l l s ( b o n e m a r r o w , s k i n , a n d in t e s t i n a l m u c o s a ) u s e t h e p e n t o s e s t o m a k e R N A , D N A , a n d s u c h c o e n z y m e s a s A T P , N A D H , F A D H 2 , a n d c o e n z y m e A .

    I n o t h e r t i s s u e s , t h e e s s e n t i a l p r o d u c t i s t h e e l e c t r o n d o n o r N A D P H , n e e d e d f o r r e d u c t i v e b i o s y n t h e s i s o r t o c o u n t e r t h e N A D P H , n e e d e d f o r r e d u c t i v e b i o s y n t h e s i s o r t o c o u n t e r t h e d a m a g i n g e f f e c t s o f o x y g e n r a d i c a l s .

    I n e r y t h r o c y t e s , t h e N A D P H p r e v e n t e d o x i d a t i v e d a m a g e t h a t a g e n e t i c d e f e c t i n g l u c o s e 6 -p h o s p h a t e d e

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