>>From: "Pedro Mendes" <prm at aber.ac.uk>
>>>In the abstract they say: "[...]we advance the idea that the rate of
>>delivery of essential nutrients to cells could be a key regulatory
>>mechanism, ...
>>From: kohn at valiant.niehs.nih.gov ("Michael Kohn")
>But in vivo, one then has to ask if the rate of perfusion (per cell)
>of a given tissue differs as markedly between species as the rate of
>metabolism (I think not) or, *if* the concentration of limiting
>nutrients vary markedly between species, why this is so. In short,
>if it's because of faster nutrient delivery, what gives rise to the
>faster delivery, and if it is metabolic processes in another tissue,
>then the answer is circular--no answer at all.
>
The issue is addressed in comparative physiology, and one (widely discussed
but still contentious) theory as that of symmorphosis - the idea that all
the physiological systems that contribute to a particular function are up-
or down-graded together when the whole function is increased or decreased.
So for diffusion of substrates in vivo, animals with faster metabolic rates
should have all processes faster - injestion, digestion, circulation,
capillary density, mitochondrial density etc. etc. This seems to me to be
essentially the point Michael is making.
Of course, this concept is close in sprit to ideas of metabolic control
analysis, where control (restriction points on flow) is widely distributed
in a pathway, and if you increase the rate of a pathway, ideally you do so
by increasing all the steps equally. Thus the concept of a "key regulatory
mechanism" in the abstract quoted by Pedro (if it implies that all of the
"regulation" (i.e. control) is at the diffusion step) may be as incorrect
as the concept of a "rate-limiting step" in more conventional metabolic
pathways.
There is an interesting paper by di Prampero and Ferretti (1990,
Respiration Physiology 80, 113-128) where they analyse the factors limiting
maximal oxygen consumption rate in humans. They appear to re-invent
control analysis and conclude that blood oxygen transport has a control
coefficient over VO2max of 0.7 in untrained subjects at sea level.
Martin Brand
Martin D. Brand
Department of Biochemistry, University of Cambridge
Tennis Court Road, Cambridge CB2 1QW UK
phone: +44 1223 333648, fax: +44 1223 333345
Internet: http://www.bio.cam.ac.uk/dept/biochem/brand/
