Medical Research Society
10 rnin after which they were treated with 10% trichloracetic acid. The samples were then stored at
-20°C prior to measurement of cyclic AMP concentration by radioimmunoassay using antibodies
obtained by injecting 2'-O-succinyl-cyclic AMP
coupled to human serum albumin into rabbits (Siddle,
Kane-Maguire & Campbell, 1973, Biochemical
Journal, 132,765).
There was no significant difference in the basal
cyclic AMP values between any of the three groups.
Following intravenous glucagon, plasma concentrations of the nucleotide rose to a peak at 15 rnin and
declined to near basal levels by 120 min.
Hyperthyroid patients showed an increased response (mean 15 min v a l u e f ~1028+85
~~
nmol/l)
as compared with controls (mean 15 min value*
SEM 534+73 nmol/l, Pc0.001).In contrast the r e
sponse of the hypothyroid patients was reduced
(mean 15 min valuefsm 252+73 nmol/l) and prolonged. These results could not be accounted for
by differences in serum insulin response. One hypothyroid patient was re-tested 3 weeks after starting
therapy with L-thyroxine, at which time she was
clinically and biochemically euthyroid. The response
in plasma cyclic AMP had changed to one similar to
that found in the euthyroid controls.
It is concluded that thyroid hormones modulate
the plasma cyclic AMP response to glucagon in man.
This response may be regarded as an index of a peripheral tissue effect of circulating thyroid hormones.
1 5 ~
for the younger group v 109+ 11 mg% for the aged;
mean blood lactate, 0.66+ 0.17 v 0.93 20.26 mmol/l;
mean 3-hydroxybutyrate, 0.03 v 013 mmol/l; acetoacetate, 0.03 f 0.02 v 0-13& 0.17 mmol/l; glycerol,
0.074kO-017 v 0130k0.070 mmol/l; serum insulin
15+7 v 21k14 pU/ml; H G H 2 3 k 1 . 9 v 2.1k2.3
ng/ml. (2) Glucose showed the most stable and ketone
bodies the least stable 24 h patterns. (3) The fluctuations of individual metabolite concentrations about
the 24 h mean increased with age. (4) Nocturnal
growth hormone peaks decreased with age.
The results show that metabolic homeostatic
mechanisms became less efficient with age. These
studies provide a useful background against which to
study intermediary metabolism in disease states.
9. THE DYNAMICS OF PROTEIN METAB-
OLISM FOLLOWING OPERATIVE TRAUMA
S. J. D. OIKEEFE,P. M. SENDER,C. G. CLARKand
W. P. T. JAMES
Department of Clinical Nutrition, London School of
Hygiene and iVopical Medicine, and Department of
Surgery, University College Hospital, London
The changes in protein turnover after surgery have
been studied to elucidate the mechanism of the
increased post-traumatic loss of endogenous nitrogen.
This must reflect a net excess of protein breakdown
over synthesis, and has generally been ascribed to an
accelerated rate of protein breakdown ('catabolic
8. METABOLIC RHYTHMS: VARIATION WITH response').
The rate of whole body protein synthesis was
AGE
measured in four patients undergoing elective
and K. G. M. M. ALBERTI abdominal surgery, both p r e and post-operatively,
A. S.ROWE,A. DORNHORST
Cowley Road Hospital and Radcliye Infirmary, Oxford from the plasma leucine flux during intravenous
infusion with ~-[l-'~C]leucine.Measurement of the
and The General Hospifal, Southampton
excretion rate of I4CO2 was used to calculate the
Intermediary metabolism in man has generally been oxidation rate of the free amino acid; values for the
assessed either after an overnight fast or by measuring synthesis and breakdown rate of protein could then be
the response to exogenous substrate loads. There is derived.
There was a consistent post-operative fall of
little information, particularly in the aged, on diurnal
blood concentrations of substrates during normal approximately 13% in the rate of protein synthesis,
activity, conventional feeding patterns and sleep. while the breakdown rate did not significantlychange.
Such information may yield valuable information These findings emphasize the need to distinguish
regarding overall metabolic homeostasis and hormone between the rate of protein breakdown and the loss of
nitrogen in the urine as a result of amino acid oxidasubstrate interactions.
tion. Breakdown rates are very much higher than
Twenty-four non-diabetic subjects, age range 25-95,
were studied in hospital but with activity unrestricted. oxidation rates so that the conservation of body
Freeflowing venous blood samples were taken a t 1 h protein depends on the etficient reutilization of amino
intervals for 24 h through an indwelling cannula and acids for protein synthesis.
Thus a fall in synthesis without any change in
assayed for glucose, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, alanine, glycerol, FFA, breakdown rates appears to be the key feature of the
metabolic response to moderate degress of operative
insulin and growth hormone.
The results showed: (1) The mean 24 h concentra- stress; these findings now provide a rational basis for
tion for all metabolites tended to increase with age therapy aimed at maintaining synthetic rates in
(mean24 h plasma glucose concentration, 8626 mg% severe protein depleting state.