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Coenzyme Q10 (CoQ10) is a terpenoid lipid that acts
as an electron carrier within the electron transport chain of the
inner mitochondrial membrane. In addition to this role in ATP production,
CoQ10 also acts as a powerful antioxidant. Because diminished CoQ10
concentrations have been associated with delayed development and
deteriorating health, several laboratories have investigated CoQ10
concentrations in different populations. We determined plasma CoQ10
levels in a pediatric population (0.5 months -17.5 years; n = 86;
37 females and 49 males), using a Waters model 2690 HPLC. We found
that the mean CoQ10 concentration was 0.79 ìg/ml, the median
was 0.76 ìg/ml, and the range was 0.28-2.19 ìg/ml.
We observed similar levels in males and females. In comparison,
a published report found that the median for adults (33-51 years)
was 1.36 ìg/ml, and the range was 0.57-3.03 ìg/ml.
This pediatric control range can be used for more accurate evaluation
of pediatric patients presenting with symptoms of CoQ10 deficiencies
and can also be used in further study of CoQ10 and its involvement
in health maintenance.
Coenzyme Q10 (CoQ10) is an isoprenoid quinone located
in the inner mitochondrial membrane (Figure
1a) of virtually all living cells. CoQ10 passes electrons from
Complexes I and II to Complex III within the electron transport
chain (Figure 1b),
playing a vital role in ATP production. CoQ10 (Figure
1c) also has antioxidant capabilities and binds damaging free
radicals. 1 Diminished CoQ10 concentrations have been associated
with muscle weakness4 and deteriorating health5, leading several
laboratories to investigate CoQ10 concentrations in different populations.
A control range for adults between 33 and 51 years was previously
established (mean = 1.36 ìg/ml, range 0.57-3.03 ìg/ml)6
to diagnose those patients with symptoms characteristic of deficiencies
(i.e., hypotonia, delayed development, seizures, lactic acidosis,
etc.).4,5,7 Because symptoms and deficiencies also occur in patients
outside that age range, there is a need to establish control ranges
in the remaining age groups. Our goal was to establish CoQ10 concentrations
in children (0-18 years) to be used as a reference for evaluating
patients with symptoms of deficiencies.
Blood samples were obtained from patients and plasma
was stored in darkness at -20¾C. CoQ10 was extracted from the plasma
using 1-propanol. Total CoQ10 was oxidized by ferric ions. Total
CoQ10 was separated by C18 reversed-phase chromatography using a
Waters HPLC system and detected using a Waters electrochemical detector.
(See Figure 2)
Each sample was run in triplicate along with two quality controls
(QC) which were used to validate each run. Samples were quantitated
(using Quattro Pro) in comparison to a six-point calibration curve.
An internal standard, diethyl CoQ (diEtCoQ), was added to each standard,
quality control, and sample.
In the pediatric population examined in this study
(n = 86; 37 females and 49 males; median age = 4.25 years), the
mean plasma CoQ10 concentration was 0.79 +/- 0.36 ìg/ml,
and the range was 0.28-2.19 ìg/ml. (See Figure
3 and Table
1) Similar values were observed in males and females (male mean
= 0.80 +/- 0.34 ìg/ml, female mean = 0.78 +/- 0.38). An overall
slight decline in CoQ10 concentration was seen with increasing age
(mean for subjects 0-3 years = 0.82 +/- 0.30 ìg/ml vs. mean
for subjects 13-17 years = 0.62 +/- 0.22). Because sample size was
not equally distributed across the age range, sub-groups were formed
for more accurate comparison. (See Figure
4) Further statistical analysis remains in progress.
In this study of a pediatric population (n = 86) a
mean plasma CoQ10 concentration of 0.79 +/- 0.36 ìg/ml was
determined with a range of 0.29-2.16 ìg/ml. By comparison,
in a published study (Laaksonen et al) the mean for adults (33-51
years) was 1.36 ìg/ml, and the range was 0.57-3.03 ìg/ml.
The reason for this difference is unclear and may reflect differences
in methodology and/or actual physiological variation. Based on previous
experience in our laboratory, the majority of patient levels tend
to be toward the lower end of this range. Similar CoQ10 values were
seen between males and females in this study. We observed a minimal
decline in CoQ10 in older patients from 0-18 years, though statistical
analysis is incomplete. The pediatric CoQ10 levels determined in
this study may be used for more accurate assessment of patients.
- Arroyo, Antonio, et al. Interactions Between Ascorbyl Free Radical
and Coenzyme Q at the Plasma Membrane. Journal of Bioenergetics
and Biomembranes. 2002; 32(2): pp. 199-210.
- Yagi, Akemi. Mitochondria. 2002. Mitochondria. 29 July 2002
.
- Miller, Karl J. Oxidative Phosphorylation: Overview of the Pathway.
1998. Metabolic Pathways of Biochemistry. 12 June 2002 .
- Baynes, John, and Marek H. Dominiczak. Medical Biochemistry.
London: Mosby, 1999; p. 91.
- Folkers, Karl, et al. Activities of Vitamin Q10 in Animal Models
and a Serious Deficiency in Patients with Cancer. Biochemical
and Biophysical Research Communications. 1997; 234: pp. 296-9.
- Laaksonen et al. Journal of Laboratory and Clinical Medicine.
1995; 125: pp. 517-21. 7. Rahman, Shamima. Neonatal presentation
of coenzyme Q10 deficiency. Journal of Pediatrics. 2001; 193(3):
pp. 456-8.
We thank the following people for help during the
completion of this project in the form of training and lab assistance:
Anne Hockenberry, Genet Tadesse, Philip Dembure and the Biochemical
Genetics Laboratory. This work was supported by the Howard Hughes
Medical Institute under Grant No. 52003071.
My research took place in a clinical laboratory which
tests patient samples for various enzyme levels and related diseases.
Coenzyme Q10 is one enzyme which the lab tests. It is a part of
the electron transport chain in the mitochondria which is essential
for the production of large quantities of the body's energy (ATP).
When a person has low levels of coenzyme Q10, the electron transport
chain cannot function and the individual has very low energy levels.
Usually, low levels of the enzyme appear in the forms of muscle
weakness, seizures, and developmental delay. The lab tests plasma
samples from the patients blood and determines the patients CoQ
level. This level is compared to a reference value (control range)
for healthy patients, and can then be treated accordingly. The reference
value used in my laboratory was taken from a study of 33-51 year
olds. Symptoms of deficiencies, however, generally appear in children.
There is little evidence to suggest that children have the same
level of plasma CoQ, so my project was to determine a control range
of plasma CoQ10 in a pediatric population. I determined the CoQ
level in 86 patients using high performance liquid chromatography
and an electrochemical detector. The chromatographer separated the
plasma allowing the CoQ to be isolated. Then the electrochemical
detector recorded a peak whose integral was proportional to the
amount of CoQ present. After 86 patients, the range of CoQ was 0.29-2.16
ug/ml which was lower than the range used in the lab. This range
will be useful in more accurately assessing children who express
deficiencies in CoQ10.
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