Danny Kohl wrote:
BUT THE THEORY IN ITS PRESENT STATE OF DEVELOPMENT DOES SUGGEST <
EXPERIMENTS. CONSIDER THE SIMPLE CASE OF A TWO ENZYME "PATHWAY" IN WHICH <
[E-1] = [E-2], AS AN EXAMPLE. IMAGINE THAT CHANNELLING OCCURS IN THIS <
PATHWAY. THE EXPERIMENTER CAN VARY [E-T] ([E-T] = [E-1] + [E-2]) OVER A <
WIDE RANGE. SINCE THE CHANNELLED PATHWAY INCLUDES TERMS WHICH ARE FIRST <
ORDER IN [E-1] (THE BINDING OF SUBSTRATE TO E-1) AND OTHER STEPS WHICH ARE<
SECOND ORDER (COMPLEX FORMATION), THE PATHWAY FLUX CAN NOT BE REPRESENTED <
BY A HOMOGENEOUS FUNCTION OF FIRST ORDER AND THUS, AS I UNDERSTAND IT, <
THERE IS NO NECESSITY FOR THE SUM OF THE CONTROL COEFFICIENTS TO BE UNITY.<
SO, IF FLUX THROUGH A PATHWAY PROCEEDS VIA A "LEAKY CHANNEL" (that is, part<
channelled, part not), THEN THE SUM OF COEFFICIENTS (WHICH WE EVALUATE AS <
THE SLOPE OF THE PLOT OF LN FLUX VS LN [E-T]) SHOULD DEPEND ON [E-T]. (SEE <
FIG 5 IN CHAPTER BY KHOLODENKO, CASCANTE & WESTERHOFF IN CHANNELLING IN <
INTERMEDIARY METABOLISM, ED. AGIUS & SHERRATT, 1997 PORTLAND PRESS). WHILE<
WE DO HAVE TO HAVE VALUES FOR RATE CONSTANTS TO EVALUATE THE FRACTION <
CHANNELLED (J-sub chan / J), IT SEEMS TO ME THAT WE CAN PROPERLY INFER THAT<
SOME PART OF THE FLUX IS CHANNELED ON THE BASIS OF THE VARIATION OF THE SUM<
OF THE CONTROL COEFFICIENTS AS A FUNCTION OF [E-T]. <
This is a seducing idea, but does it have enough theoretical background? For
instance, how can one distinguish between effects caused by channelling and
those due to inhibitors or activators with variable concentrations?
I suspect that Paul Schlosser's "Black Frame" analysis deals with this
kind of problems. He is going to send it to me and then I will be able to
comment competently.
Pentcho
