VoI. 72, No. 3, 1976

CYCLIC

BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS

NUCLEOTIDE- r PYRUVATE-

PYRUVATE

Theo

J.C.

KINASE

ACTIVITY

van Berkel,

Johan

Received

July

CHANGES

IN

RAT H E P A T O C Y T E S

Johan

F. K o s t e r

and

C. H ~ i s m a n n

of B i o c h e m i s t r y versity

IN I S O L A T E D

K. K r u i j t ,

Willem

Department

AND HORMONE-INDUCED

I, F a c u l t y

Rotterdam,

of M e d i c i n e ,

Erasmus

Uni-

The Netherlands

27,1976

SUMMARY. I n c u b a t i o n of i s o l a t e d rat h e p a t o c y t e s w i t h g l u c a g o n (10 -6 M), d b - c A M P (0.I mM) and d b - c G M P (0.I mM) c a u s e s a d e c r e a s e in p y r u v a t e k i n a s e a c t i v i t y of 46, 49 and 34% r e s p e c t i v e l y , w h e n m e a s u r e d at 1 mM Mg~ • + ree and s u b o p t i m a l s u b s t r a t e ( P - e n o l p y r u v a t e ) c o n c e n t r a t i o n s , w h 1 ~ e the Vma x is u n l n f l u e n c e d . An i n c r e a s e in a c t i v i t y (25%) is n o t i c e d w h e n the cells are i n c u b a t e d w i t h 1 mM p y r u v a t e . The g l u c a g o n i n a c t i v a t e d e n z y m e (Lb) shows a d e c r e a s e d a f f i n i t y for the s u b s t r a t e P - e n o l p y r u v a t e and for the a l l o s t e r i c a c t i v a t o r F r u - l , 6 - P 2 as c o m p a r e d to the a c t i v a t e d form (La). The n a t u r e of the h o r m o n e and c y c l i c n u c l e o t i d e - i n d u c e d c h a n g e s in p y r u v a t e k i n a s e is d i s c u s s e d . It is c o n c l u d e d that the P - e n o l p y r u v a t e cycle is u n d e r c o m p a r a b l e acute h o r m o n a l c o n t r o l as the F D P a s e - P F K cycle. Both cycles are l i n k e d by the c o m m o n e f f e c t o r F r u - l , 6 - P 2 m a k i n g not only d i r e c t but also i n d i r e c t h o r m o n a l control of p y r u v a t e k i n a s e flux p o s s i b l e . Pyruvate catalyses in the

kinase

the

last

regulation

step

two

hepatocytes

enzyme

From kinetic perties

sequence vator

only

studies

enzyme

during

of the high

itself

can

proposed. changes

influence

parenchymal Taunton

et

types

the

concluded

could

affinity

of the

It was

suggested

its

affinity

al.

to test

(7,8)

in Vma x of p y r u v a t e

not

Copyright © 1976 by Academic Press, Inc. All rights of reproduction in any iorrn reserved.

enzyme

917

that

that

lead

this

may

(I),

enzyme to i n a c t i v a t e (3-6).

the k n o w n

pro-

to the p r e s e n c e

of

This

was

mainly

the

con-

for

its

allosteric

acti

"A change and

possibility

recently be

gly-

uncertain

for F r u - l , 6 - P 2 "

showed

kinase

This

is still

and kinase

the m e c h a n i s m

gluconeogenesis.

cells

(2).

2.7.1.40)

is i m p o r t a n t

of p y r u v a t e

L-type but

it was

kinase

activity

EC

gluconeogenesis

conditions

in v i t r o

pyruvate

F r u - l , 6 - P 2 (6).

isolated

contain

properties

gluconeogenic

of L - t y p e

an i n a c t i v e

contains

regulatory

under

Its

liver

isolated

the

of g l y c o l y s i s .

between

Although

many

phosphotransferase,

of the b a l a n c e

colysis.

possesses

(ATP:pyruvate

that

induced

by

in the the

was

enzyme

use

of

therefore

short

term

alteration

of

Vol. 72, No. 3, 1976

the h o r m o n a l that

state

cyclic-AMP

in the vate

intact

kinase

effect ation we

of the

induces

liver

was

of the

ratio

can be

by

kinase

of F D P a s e

of p y r u v a t e both

while

Rognstad

of the p y r u v a t e

Howeverp

a direct

Clark flux

as

suggested

activities.

direct

which

and

flux

rate

on p y r u -

an i n d i r e c t of an a l t e r -

In the p r e s e n t effects

suggests

indirect

showed

effect

a consequence

and h o r m o n e - i n d u c e d

kinase

(9)

kinase

hormonal

(I0) w h o rate

and PFK

nucleotide-

under

animal,

inhibition

questioned

cyclic

tic p r o p e r t i e s

intact

cell.

on the p y r u v a t e

report

flux

BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS

that

hormonal

paper

on the k i n e -

pyruvate

kinase

control.

MATERIALS AND METHODS. I s o l a t e d rat l i v e r h e p a t o c y t e s w e r e p r e p a r e d f r o m fed a n i m a l s e s s e n t i a l l y as d e s c r i b e d by B e r r y and F r i e n d (11), m o d i f i e d as d e s c r i b e d p r e v i o u s l y (12). The p a r e n c h y mal cells w e r e i n c u b a t e d at 37°C in 50 ml E r l e n m e y e r f l a s k s s t o p p e r e d w i t h r u b b e r caps. The i n c u b a t i o n m e d i u m was 10 ml of K r e b s - R i n g e r b u f f e r c o n t a i n i n g the a d d i t i o n s as i n d i c a t e d in the f i g u r e s . At the i n d i c a t e d times 2 ml s a m p l e s w e r e w i t h d r a w n , h o m o g e n i z e d i m m e d i a t e l y and put in i c e - w a t e r . Zero time c o n t r o l s c o n t a i n e d all the a d d i t i o n s but no i n c u b a t i o n at 37°C was p e r f o r m e d . A f t e r t e r m i n a t i o n of the i n c u b a t i o n (the total time did not e x c e e d 50 min) the h o m o g e n i z e d cells w e r e c e n t r i f u g e d for 10 m i n at 10.000 g and the s u p e r n a t a n t was i m m e d i a t e l y t e s t e d for p y r u v a t e k i n a s e a c t i v i t y by a d d i n g 0.5 ml s u p e r n a t a n t to a c u v e t t e c o n t a i n i n g 24 m M T r i s - H C l pH 7.5, 200 m M KCI, l m M ADP 0.1 mg l a c tate d e h y d r o g e n a s e , 0.4 m M N A D H and l mM free Mg 2+. The free Mg 2+ c o n c e n t r a t i o n was c a l c u l a t e d as d e s c r i b e d e a r l i e r (13). The r e a c t i o n was s t a r t e d by a d d i n g p h o s p h o e n o l p y r u v a t e (final c o n c e n t r a t i o n 2.5 mM) a f t e r 5 min p r e i n c u b a t i o n . This s e q u e n c e of a d d i tions is e s s e n t i a l b e c a u s e b o u n d F r u - 1 , 6 - P 2 w i l l be split off u n d e r the a p p l i e d h i g h salt c o n c e n t r a t i o n in the a b s e n c e of P - e n o l p y r u v a t e (12,14). L i n e a r c u r v e s w e r e o b t a i n e d by this a d d i t i o n s e q u e n c e t h r o u g h o u t this study. W h e n i n d i c a t e d F r u - l , 6 - P 2 (0.5 m M final c o n c e n t r a t i o n ) was a d d e d as s e c o n d a d d i t i o n .

RESULTS Fig.

1 shows

of p y r u v a t e

kinase

l mM pyruvate. kinase

causes

when

the

It can be

activity

incubation. AMP

the e f f e c t

The a 50%

at

presence

that

This

of

decrease

cyclic

isolated

seen

10 min.

of d i b u t y r y l - c y c l i c - G M P

of

liver

alter

alone

+ 0.1

kinase the

V

on the

are

however,

l mM pyruvate

not

cells

pyruvate

effect,

of p y r u v a t e

does

nucleotides

activity

incubated

raises

the p y r u v a t e

disappears mM

on f u r t h e r

dibutyryl-cyclic-

activity.

effect

with

The

addition

of d b - c A M P .

When

v a l u e s are m e a s u r e d at s a t u r a t i n g F r u - l , 6 - P 2 c o n c e n t r a t i o n s max n e i t h e r d b - c A M P a l o n e nor its c o m b i n a t i o n w i t h d b - c G M P h a v e an effect

on the m a x i m a l

enzymatic

activity.

918

V o l . 7 2 , N o . 3, 1 9 7 6

BIOCHEMICAL AND

B I O P H Y S I C A L RESEARCH C O M M U N I C A T I O N S

-1 -1 nmoles m~n mg 125

1

1 mM pyr. + db-cAMP + db-cGMP

1 mM pyr. + db-cAMP

mM pyr.

100

75

50



0

25

lo

2o

4'o

I

I

I

10

20

40

,0

2'o

4o

time (m~nutes)

Fig. ] I n f l u e n c e of p y r u v a t e , p y r u v a t e + d b - c A M P (0°I mM) and pyruvate+db-cAMP (0.1 mM) + d b - c G M P (0.I mM) on the p y r u v a t e k i n a s e a c t i v i t y of i s o l a t e d h e p a t o c y t e s . The a d d i t i o n s to inc u b a t i o n s of i n t a c t cells are i n d i c a t e d in the figure. For f u r t h e r i n c u b a t i o n s see M A T E R I A L S AND M E T H O D S . The open symbols r e p r e s e n t the p ~ u v a t e k i n a s e a c t i v i t y at 2.5 mM P - e n o l p y r u v a t e and 1 m M M g ~ r e e . The c l o s e d s y m b o l s r e p r e s e n t the a c t i v i t y a f t e r s u b s e q u e n t a d d i t i o n of F r u - 1 , 6 - P 2 (0.5 mM).

nmoles rain-1 mg-1

125

10 mM glucose + insulin

1 mM pyr. + glucagon

150

1

100 75

A

50' ~

~

25 0

~

,

i

5

10

1S

I

0

5

i

I

10

15

I

5

I

I

10 15 time (minutes)

Fig. 2 I n f l u e n c e of p y r u v a t e + d b - c G M P (O.l mM), p y r u v a t e + g l u c a g o n (lO -6 M) and g l u c o s e + i n s u l i n (4 mU/ml) on the p y r u v a t e k i n a s e a c t i v i t y of i s o l a t e d h e p a t o c y t e s . The additions to i n c u b a t i o n s of intact cells are i n d i c a t e d in the figure. For f u r t h e r i n c u b a t i o n c o n d i t i o n s see M A T E R I A L S AND M E T H O D S . The open s y m b o l s r e p r e s e n t the p y r u v a t e k i n a s e activ i t y at 2,5 mM P - e n o l p y r u v a t e + l mM M g ~ e e . The c l o s e d symbols r e p r e s e n t the a c t i v i t y a f t e r s u b s e q u e n t a d d i t i o n of F r u - l , 6 - ~ 2 (0.5 mM).

919

Vol. 72, No. 3, 1976

TABLE

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

I

EFFECT

OF M g

2+

A N D F R U - I , 6 - P 2 ON T H E

HORMONE-INDUCED

CHANGES

IN P Y R U V A T E

CYCLIC NUCLEOTIDEKINASE

Additions

to i n c u b a t i o n s

Activity

of i n t a c t

cells

1 m.MMg2+ free

i mid pyr.

AND

ACTIVITY

+i0 m M M g 2+

at

+I0

mM Mg

+0.5 mM Fru1,6-P 2

72.8

138.4

164.3

i m M pyr.

+ 0.i m M d b - c A M P

33.7

103.0

160.9

I m M pyr.

+ 0.i m M d b - c G M P

42.6

109.7

158.9

i m M pyr.

+ 10 -6 M g l u c a g o n

i0 m M g l u c o s e i0 m M g l u c o s e

When

shown

added been

+ insulin (4 m U / m l )

to be p r e s e n t

to the

incubated

first

column.

Fig. pyruvate

for

2 shows kinase

that

0.I

activity.

the

cleotides

causes

a decrease

taken

place

liver

cell

forms

of p y r u v a t e

the

enzymes

nucleotides

in the

thiol and

the h o m o g e n a t e s

is not

involved

and T i t a n j i

133.4

158.7

the

intact We

hand,

kinase

exist

groups

(5,14).

were

prepared

suggesting

in the o b s e r v e d et

al.

(]6)

the

the

than

TABLE

of

I);

that Fig.

cyclic

Insulin

that

upon the

cells

2

nu-

in the p r e -

shown

that

compounds

the

redox

effects

to the

state

of the

unaltered

or p r e s e n c e

of e s s e n t i a l

Recently that

had

interconvertible

were

absence

effects.

changes

several

oxidation

920

smaller

also

of the

However,

have

is

as well.

earlier

in the

decreases

instead

depending

that

in the

m g -I p r o t e i n .

also

(see

had

is i n e f f e c t i v e .

added

on i n t a c t

cells

mentioned

effect

the n a t u r e

reported

of g l u c a g o n

its

intact

m i n -I

itself

in a c t i v i t y

cell we

the

substances

in n m o l e s

of d b - c A M P

other

0.5 m M F r u - l , 6 - P 2 w e r e

after

of g l u c a g o n

to e x p l o r e

homogenate.

mercaptoethanol,

(15)

addition

of g l u c o s e s on the

In an a t t e m p t

64.6

However,

concentration

sence

159.6

mM db-cGMP

also

that

162.4

expressed

of an e q u i m o l a r shows

99.5 129.1

prepared

I0 m i n w i t h

Activity

37.7 62.4

i0 m M M g 2+ a n d / o r

cell homogenates

2+

under

cyclic

whether

of

10 m M

-SH

groups

Ljungstrom certain

of

et al.

condi-

Vol. 72, No. 3, 1976

tions

liver p y r u v a t e

panied

kinase

by a d e c r e a s e

optimal other

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

can be p h o s p h o r y l a t e d ,

of activity,

P-enolpyruvate

especially

concentrations

(16).

which

is accom-

when measured

at sub-

The p h o s p h o r y l a t i o n

of

enzymes,

bation

such as p y r u v a t e d e h y d r o g e n a s e is r e v e r s e d by incu2+ at high Mg c o n c e n t r a t i o n s (17,18) w h i c h activates p h o s p h o -

protein

phosphatases.

concentrations

TABLE

I illustrates

on the enzyme

a c t i v i t y • At

the effect

of high Mg 2+

! mM M gfree 2+

the effects

of cyclic n u c l e o t i d e s and hormones are maximal, a d d i t i o n of 10 mM 2+ Mg causes a prompt (within 10 sec) s t i m u l a t i o n of p y r u v a t e kinase activity. cyclic

However,

even

nucleotides

1,6-P 2 relieves TABLE

and h o r m o n e s

these

the enzyme

by g l u c a g o n obtained

the changes treatment

after

w h i ~ L a is the enzyme

pyruvate

(I mM)

TABLE

alone.

of k i n e t i c

of the

incubation

glucagon

in affinity

may be observed.

the effects o f

Addition

of Fru-

differences.

II summarizes

vate kinase

at high Mg 2+ c o n c e n t r a t i o n s

It can be

for the s u b s t r a t e

liver

of the

obtained seen

properties cells•

cells

from cells

that besides

P-enolpyruvate,

for

of pyru-

L b stands

10 min with

incubated

with

the d i f f e r e n c e

the L b form also

II

COMPARISON

OF T H E K I N E T I C

PARAMETERS

OF P Y R U V A T E

KINASE

TYPES

L a AND L b

La K0. 5

P-enolpyruvate

K0.5a Fru-l,6-P 2 K0.5a Fru-l,6-P 2 in p r e s e n c e of A T P and a l a n i n e

L b was

prepared

+ glucagon

(10 -6 M)

L a was p r e p a r e d 1 mM pyruvate

Lb

2.2 m M

4.1 m M

0.6 ~M

1.0 ~ M

4.2 ~ M

9.8 ~M

(2 mM) (i mM)

by i n c u b a t i o n

of the cells w i t h

1 mM pyruvate

for i0 m i n

by i n c u b a t i o n

of the cells

alone.

921

for

for i0 m i n w i t h

Vol. 72, No. 3, 1976

possesses

BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS

a lower

apparent

Fru-l,6-P 2 especially tions

of the

affinity

for

in the p r e s e n c e

allosteric

inhibitors

the

allosteric

activator

of p h y s i o l o g i c a l

ATP

(2 mM)

and

concentra-

alanine

(I mM)

(6,19).

DISCUSSION Taunton on the

enzymatic

pyruvate firmed

kinase

can

(21).

L-type from

zyme

should

be

as

fully

enzyme 2+ Mgfree

inactivated

enzyme

form

kinase,

enzyme.

will

gluconeogenic

(6).

The

The

the

The

of

1 mM

lower

conversions

may

and

was

con-

and

isolated to

studies

hepato-

study with

the

iso-

concluded

by e x t r a p o l a -

situation

that

both

glycolytic

show

with

that

properties

forms of

the

liver

distinct

cell from

an the

of the L b f o r m of p y r u v a t e

for

the

liver

allosteric kinase cells

of the

identical

summarized

gluconeo-

parameters

in the

of p y r u v a t e of

the en-

at the p h y s i o l o g i c a l

properties

affinity

and

interconvertible kinetic

to an a c t i v a t i o n

be

(20)

that

as d e t e r m i n e d

properties

FDPase This

we

Incubation

leads

kinetic

effects

in v i v o

that

a decrease

conditions.

rapid

as a m o d e l

earlier

reported

(22),

described

the

our

under (6)

show

(6),

(2,5,6,19) to

glucagon,

enable

surprisingly

form possesses

data

From

can be p r e s e n t

especially

Fru-l~6-P2,

earlier

suggested

by

concentration

purified

kinase

and B l a i r

experiments

kinase.

in vivo.

to o b s e r v e

of h o r m o n e s .

Cimbala

activated

We

be p r e s e n t

(Lb)

by

suggested

in v i t r o

conditions.

first

of p h o s p h o f r u c t o k i n a s e ,

The p r e s e n t

should

(l mM)

kinase

pyruvate

the

the

the a d m i n i s t r a t i o n

of p y r u v a t e

tion

genie

activities by

serve,

regulation lated

(7,8) w e r e

for p y r u v a t e

Friedrichs cytes

et al.

activator

activity

with

under

pyruvate

enzyme.

This

La enzyme

to the p u r i f i e d

as f o l l o w s :

glucagon db-cAMP (db-cGMP) La x (active form) The m e c h a n i s m clear the

of the

at the m o m e n t .

thiol

groups

into

the L a form.

transition

Regulation

of the

of the L b f o r m w i t h

Lb (inactive

pyruvate

enzyme

between

by m e a n s seems

Recently

it was

922

shown

L b and L a f o r m

of the

less

10 m M m e r c a p t o e t h a n o l

form)

reduction

probable did not

that

as

of

incubation

convert

pyruvate

is not state

this

kinase

form

from

Vol. 72, No. 3, 1976

rat

liver

into

BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS

(15,16)

and

chicken

a phosphorylated,

catalysed present

by a cAMP

paper

that

is d i m i n i s h e d enzyme

in intact

by g l u c a g o n

it is possible

endogenous rylationp binding et al.

of other (24)

This

vitro

it is only

zyme.

that

of such

link hormone

activity

tion

recently through tate

to both

under

pyruvate

for p y r u v a t e

the F D P a s e - P F K

the k i n e t i c

cyclic

gluconeogenic at high

for g l u c o n e o g e n e s i s ~ no effect

(27)

pyruvate

state

that with

necessary

for the t r a n s f e r

(28).

occurrence

The

that with

of p y r u v a t e direct

FDPase-PFK

couple,

can be

tides,

which

Fru-Ip6-P2~

effect

(lO) who

kinase

pyruvate kinase

kinase

activity

could

in

(25).

to the en-

(26).

and

the

The

possibly

the p y r u v a t e

Rognstad cAMP

(9)

showed the f l u x

With

the p y r u v a t e

of cAMP

is noticed.

equivalents cycle

in rela-

inhibited

concentrations.

as s u b s t r a t e

of hormones

on p y r u v a t e

lackinase

Katz

cycle

and is

to the cytosol

is s t r e n g t h e n e d

by our

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

of PFK

on p y r u v a t e

an indirect kinase.

directly

to an enzyme

by g l u c a g o n

and the

dependent

923

kinase

influence,

Our data

form with

that under p h y s i o l o g i c a l is largely

of p y r u v a t e

is a t t r a c t i v e

the

increases.

suggests

the product

earlier

acids

the P - e n o l p y r u v a t e

of reducing

of such a useful

influenced lead

showed

Pilkis

although

properties

however,

low and c o n s e q u e n t l y

ed by Clark

cycle

conditions

pyruvate

flux was

activity

kinase

the

inside

concentrations fatty

nucleotides

Rognstad

The

Recently

of

phospho-

influencing

kinase,

high

of free

of liver m e t a b o l i s m .

kinase

as s u b s t r a t e

observation

the b r e a k d o w n Besides

for p h o s p h o f r u c t o k i n a s e

to influence and/or

regulation

that

to be d e t e r m i n e d ~

Ca 2+ t r a n s p o r t

of p y r u v a t e

on

efficiency

cycle.

by hormones

to the

compounds.

promotes

kinase

be based

a lower

prevent

action by

at r e l a t i v e l y

a mechanism

The p o s s i b ~ i t y kinase

their

is the b i n d i n g

suggested

actions

remains

added will

weight

glucagon

effective

has been

occurrence

exert

is an i n h i b i t o r

possibility

of cGMP

indeed

has

is

of the

of p y r u v a t e

could

which

findings

of p h o s p h o d i e s t e r a s e .

low m o l e c u l a r

cation

This

kinase

an effect

also

then

in vitro

phosphorylation The

the a c t i v i t y

db-cGMP,

db-cGMP

This

kinase.

and db-cAMP

that

may

showed

cell.

A further

cells

cAMP by i n h i b i t i o n hormones

form.

protein

Whether

represents

(23) may be c o n v e r t e d

active,

dependent

phosphorylation.

than db-cAMPp since

less

liver

show

and/or

a lowered

substrate

this

is q u e s t i o n by the

that p y r u v a t e cyclic

affinity

nucleofor

for FDPase.

conditions

upon

flux

mediated

We

the p y r u v a t e

compound.

This

in-

Vol. 72, No. 3, 1976

dicates

that

glucagon

a relation

can regulate

influencing encing

BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS

the

exists

between

the pyruvate

affinity

kinase

for Fru-1,6-P2,

the Fru-l,6-P 2 c o n c e n t r a t i n n

FDPase-PFK

the two cycles,

itself

flux both

in which

directly,

and indirectly through

by

by influ-

the balance

of

activities.

ACKNOWLEDGEMENTS. Miss A.C. Hanson is thanked for her help in the p r e p a r a t i o n of the manuscript. The Netherlands Foundation for Fundamental Medical Research (FUNGO) is acknowledged for partial financial support (grant 13-39-18).

REFERENCES I. Tanaka, T., Harano, Y., Morimura, H. and Mori, R. (1965) Biochem. Biophys. Res. Commun. 21, 65-70. 2. Van Berkel, Th.J.C., Koster, J.F. and H~Ismann, W.C. (1972) Biochim. Biophys. Acta 276, 425-429. 3. Kutzbach, C., B i s c h o f h e r g e r , H., Hess, B. and ZimmermannTelschow, H. (1973) H o p p e - S e y l e r ' s Z. Physiol. Chem. 345, 1473-1489. 4 Llorente, P . , M a r c o , R. a n d S o l s , A. ( 1 9 7 0 ) E u r . J . B i o c h e m . 13, 4 5 - 5 4 . 5 Van B e r k e l , Th.J.C., Koster, J.F. a n d H ~ i s m a n n , W.C. ( 1 9 7 3 ) Biochim. Biophys. Acta 293, I18-124. 6 Van B e r k e l , Th.J.C.) Koster) J.F., Kruijt, J.K. and Hulsmann) W.C. ( 1 9 7 4 ) B i o c h i m . B i o p h y s . Acta 370, 450-458. 7 Taunton) O.D., Stifel, F.B.) Greene, H.L. and Herman, R.H. (1974) J. Biol. Chem. 2 4 9 , 7 2 2 8 - 7 2 3 9 . 8 Stifel, F.B., Taunton, O . D . ) G r e e n e ) H . L . a n d H e r m a n , R.H. (1974) J. Biol. Chem. 2 4 9 , 7 2 4 0 - 7 2 4 4 . R. ( 1 9 7 5 ) B i o c h e m . B i o p h y s . R e s . Commun. 6 3 , 9 0 0 9 Rognstad) 905. 10 Clark, M.G. (1976) Biochem. Biophys. Res. Commun. 68, 120126. Berry. M.N. and Friend, D.S. (1969) J. Cell Biol. 43, 50611 520. 12 Van Berkel, Th.J.C., Kruijt, J.K. and Koster, J.F. (1975) Eur. J. Biochem. 58, 145-152. 13 Van Berkel, Th.J.C. (1974) Biochim. Biophys. Acta 370, 140152. 14 Kutzbach, C. and Hess, B. (1970) H o p p e - S e y l e r ' s Z. Physiol. Chem. 351, 272-273. Ljungstrom, 0., Hjelmquist, G. and Engstrom) L. (1974) 15 Biochim. Biophys. Acta 358, 289-298. 16 Titanji, V.P.K., Zetterqvist, O. and Engstr~m, L. (1976) Biochim. Biophys. Acta 422, 98-108. 17 Hucho, F.) Randall, D.O., Roche, T.E., Burgett) M.W., Pelley) J.W. and Reed, L.J. (1972) Arch. Biochem. Biophys. 151, 328-340 Siess, E.A. and Wieland, O.H. (1973) Eur. J. Biochem. 26, 9618 105. Van Berkel, Th.J.C., Kruijt, J.K. and Koster, J.F. (1975) FEB8 19 Lett. 52, 312-316. Cimbala, M. and Blair) J.B. (1975) Fed. Proc. 34, 618. 20

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21. 22.

Friedrichs, D. (1975) FEBS Meeting, Paris, Abstract no. ]455. Veloso, D., Guynn, R.W., Oskarsson, M. and Veech, R.L. (1973) J. Biol. Chem. 248, 4811-4819. 23. Eigenbrodt, E. and Schoner, W. (1975) H o p p e - S e y l e r ' s Z. Physiol Chem. 356, 227-228 (Abstract). 24. Pilkis S.J., Claus, T.H., Johnson, R.A. and Park, C.R. (1975) J. Biol. Chem. 250, 6328-6336. 25. Gabrielli, F° and Baldi, S. (]972) Eur. J. Biochem. 31, 209214. 26. Ramadoss, C.S., Uyeda, K. and Johnston, J.M. (1976) J. Biol. Chem. 251, 98-107. 27. Katz, J. and Rognstad, R. (]976) in Current Topics in Cellular Regulation (eds. Horecker, B.L. and Stadtman, E.A.) pp. 237-289 Academic Press, New York. 28. Meyer, A.J. and Williamson, J.R. (]974) Bioehim. Biophys. Acta 333,

1-ll.

925

Cyclic nucleotide-, pyruvate- and hormone-induced changes in pyruvate kinase activity in isolated rat hepatocytes.

VoI. 72, No. 3, 1976 CYCLIC BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS NUCLEOTIDE- r PYRUVATE- PYRUVATE Theo J.C. KINASE ACTIVITY van...
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