42 J.A. Rathmacher
Table 2.2.Steady-state compartment masses and mass transfer rates of a three-compartment model of
3-methylhistidine (3MH) metabolism.
Parameter Human Cattle Swine Sheep Dogs
n 4392040 5
Plasma 3MH, μM 2.9 8.6 10.4 36.9 21.8
M 1 , nmol kg1a 603 807 1,110 5,308 3,227
M 2 , nmol kg^1912 2,291 2,857 12,483 7,973
M 3 , nmol kg^1 7,938 8,079 6,151 17,017 9,261
R 21 , nmol kg^1 min1b 51 101 247 944 319
R 12 , nmol kg^1 min^153105247946329
R 32 , nmol kg^1 min^1 7.9 5.8 37 81 56
R 23 , nmol kg^1 min^1 9.6 9.9 32 77 56
R 01 , nmol kg^1 min^1 2.2 4.1 NA 1.4 9
R 03 , nmol kg^1 min^1 NA NA 5.0 5.8 NA
3MH productionc, μmol kg^1 day^1 3.1 6.0 7.2 10.3 12
aM
b i= compartment mass I.
Rij= mass transfer rate from compartment j and i.
c3MH production was obtained from the model.
calculated by the model in Table 2.2. An
important feature of these models is the
description of 3MH metabolism within the
body. The significance of mass transfer
rates and compartment sizes is not fully
understood. However, the model para-
meters and mass transfer rates may explain
the failure of sheep and swine to
excrete 3MH quantitatively in the urine
(Rathmacher and Nissen, 1992). Three
mechanisms may explain the failure of
sheep and swine to excrete 3MH: (i) 3MH
transport between the compartments limits
the excretion of 3MH; (ii) 3MH is
reabsorbed avidly by the kidney; and (iii)
enzymatic conversion of 3MH to balenine
is enhanced. In comparing the data from
Tables 2.1 and 2.2, the low rate of 3MH
excretion in sheep and swine is not due to
impaired transfer of 3MH out of and
between compartments. Cattle appear to
have a slower exchange of 3MH between
tissues despite near quantitative urinary
excretion. The most likely reason for
sequestering of 3MH in sheep and swine is
that the kidneys are very efficient in
conserving 3MH, which in turn increases
the compartment size and plasma concen-
tration, and through mass action could
increase the synthesis of balenine.
The models described represent a
framework and methodological approach
describing steady-state 3MH kinetics in the
whole animal and constitutes a working
theory for testing by further experimenta-
tion using designs which alter muscle
protein breakdown. The rate of 3MH
production is an important tool in under-
standing the regulation of muscle protein
degradation. The advantages of these
models are that: (i) they do not necessitate
quantitative urine collection (plasma
model); (ii) they reduce error due to the
frequency of plasma sampling versus the
infrequency of urine collection in other
models; (iii) they are more quantitative and
measure the total production rate indepen-
dently of the determination of free or
conjugated forms; (iv) they give informa-
tion about pool size and transfer rates; (v)
they establish a relationship to muscle
mass; (vi) they provide a method for direct
measurement of muscle proteolysis in
swine and sheep; and (vii) they do not
require restraint of the animals for long
periods.Significance of Protein Turnover
Since isotopes were first used by
Schoeheimer and his colleagues in 1940,
many aspects of protein turnover have
been described. The methods described in