section 17.3
Metabolism of Some Individual Amino Acids
349
are brain, prostate, gut, lung, bladder, uterus, placenta,
and thyroid; those rich in CK-3 are skeletal and car-
diac muscle. Cardiac muscle contains significant amounts
of CK-2 (25-46% of total CK activity, as opposed to
less than 5% in skeletal muscle), so that in myocardial
infarction the rise in serum total CK activity is accompa-
nied by a parallel rise in that of CK-2 (Chapter 8).
Phosphocreatine undergoes a slow and nonenzymatic
cyclization to creatinine.
N H — P 0 32'
I
c =
n h 2 +
I
N — CH
3
+ H + -
i
CH
2
I
cocr
P h o sp h o c r e a tin e
\
/
N --------CH
2
/
H3C
+ PiJ~ + H20
C reatinine
Creatinine has no useful function and is eliminated by
renal glomerular filtration and to a small extent by renal
tubular secretion. Creatinine clearance approximately par-
allels the
glomerular filtration rate
(GFR) and is used as
a kidney function test. It is calculated as follows:
urine creatinine (mg/L)
Creatinine clearance = --------------------------------
plasma creatinine (mg/L)
x urine volume per unit time
Creatinine concentrations are measured from a pre-
cisely timed urine specimen (e.g., 4-hour, 24-hour) and
a plasma specimen drawn during the urine collection
period. Excretion of creatinine depends on skeletal mus-
cle mass and varies with age and sex. However, day-to-
day variation in a healthy individual is not significant.
Creatinuria,
the excessive excretion of creatine in urine,
may occur during growth, fever, starvation, diabetes melli-
tus, extensive tissue destruction, muscular dystrophy, and
hyperthyroidism.
regenerates ATP from ADP, thereby maintaining a high
level of ATP required during intense exercise. A large pool
of phosphocreatine resides in the skeletal muscle. It has
been theorized that in order to maximize phosphocreatine
stores in the skeletal muscle to replenish ATP during rapid
muscle contractions, an exogenous source of creatine may
be beneficial.
Double-blind placebo-controlled studies of oral sup-
plementation of creatine in human subjects have shown
increased performance during short duration, strenuous,
high-intensity exercise. Such activities require that ATP
be replenished rapidly from phosphocreatine stores during
anaerobic metabolism. These studies usually consisted of
ingestion of 20 g of creatine per day for 5 days followed
by a maintenance dose of 5-10 g/day. Studies on crea-
tine as an ergogenic aid have not been uniformly positive;
some have shown no beneficial effect and still others have
been equivocal and indicated that creatine supplementa-
tion did not enhance athletic activities. The safety issues
of long-term creatine supplementation on kidney, liver,
nerve, muscle, and other tissues are not known.
Serine
Synthesis of
serine
from 3-phosphoglycerate, an inter-
mediate of glycolysis (Chapter 13), requires oxidation
of 3-phosphoglycerate
to
3-phosphohydroxypyruvate,
transamination of 3-phosphohydroxypyruvate by glu-
tamate, and hydrolysis of 3-phosphoserine to serine
(Figure 17-11). This cytosolic pathway is regulated by
inhibition of phosphoserine phosphatase by serine. Serine
is converted to pyruvate by cytosolic serine dehydratase.
More importantly, it is converted in mitochondria to
2-phosphoglycerate by way of hydroxypyruvate and
D-glycerate; and the enzymes involved are a transam-
inase, a dehydrogenase, and a kinase. Serine is in-
terconvertible with glycine (Figure 17-10) and is in-
volved in phospholipid (Chapter 19) and in cysteine
synthesis.
Use of Creatine as a Dietary Supplement
The creatine pool in the human body comes from both
endogenous synthesis and the diet which provides 1-2 g.
Red meat provides large amounts of dietary creatine and
vegetables a limited amount. Using glycine, arginine, and
methionine, creatine is synthesized in the liver, pancreas,
and kidney. Creatine transported in blood crosses muscle
and nerve cell membranes by means of a specific crea-
tine transporter system against a concentration gradient of
200:1. Intracellularly, creatine is converted to phosphocre-
atine by ATP, a reaction catalyzed by creatine kinase. Phos-
phocreatine, with its high phosphoryl transfer potential,
Proline
Proline
arises from and gives rise to glutamate. Synthesis
is by reduction of glutamate to glutamate-y -scmialdehyde
by way of an enzyme-bound y -glutamyl phosphate. The
y -semialdehyde spontaneously cyclizes to A'-pyrroline-
5-carboxylate, which is then reduced by NAD(P)H to pro-
line (Figure 17-12). Proline is converted to A'-pyrroline-5-
carboxylate by proline oxidase, which is tightly bound to
the inner mitochondrial membrane in liver, kidney, heart,
and brain. A'-Pyrroline-5-carboxylate is in equilibrium
with glutamate-y-semialdehyde, which can be transami-
nated to ornithine or reduced to glutamate (Figure 17-12).
