GSSG ratios are associated with greater ca-
pacity to cope with oxidative stress (4).
PPP is a superb source of the reducing
power needed for antioxidation because it
requires relatively little energy. The synthe-
sis of NADPH through PPP requires a single
ATP to produce glucose 6-phosphate. Its by-
products can be redirected into glycolysis if
they are not used in biosynthesis.
Levin et al. based their conjecture of the
involvement of PPP in oxidative damage
protection in hawkmoths on a curious ob-
servation. When animals are catabolizing
carbohydrates, such as the sugars in nectar,
their respiratory quotient (RQ, the ratio of
CO2 production to O2 consumption) should
be 1. Yet in many nectar-feeding animals,
the value is often much higher. The com-
mon explanation for this observation is
that the animals are not only catabolizing
carbohydrates but also synthesizing lipids.
However, there is an alternative—or, rather,
complementary—explanation: The oxida-
tive phase of the PPP decarboxylates carbon
1 of glucose 6-phosphate and generates CO2,
thus increasing the rate of CO2 production
without altering O2 consumption.
To determine whether the latter explana-
tion is correct, Levin et al. fed hawkmoths
(Manduca sexta) a sugar solution contain-
ing glucose in which carbon 1 was enriched
in the isotope 13C. They then measured both
RQ and the isotopic composition of ex-
haled CO2. Fed moths at rest had high RQ
values and produced highly 13C-enriched
CO2. Active moths had lower RQ values and
produced CO2 that was less 13C enriched.
Because the PPP selectively converts carbon
1 into CO2, these observations support the
hypothesis that high RQ is due to the PPP.
Levin et al. also found that after exercise,
fed moths had higher GSH/GSSG ratios and
lower levels of protein and lipid oxidative
damage than unfed moths. These observa-
tions are consistent with increased anti-
oxidant activity fueled by NADPH from the
PPP (see the figure).
The sweet oxidative relief experienced by
hawkmoths might be a characteristic shared
with other animals. During migratory flights,
animals experience prolonged bouts of stren-
uous activity, elevating oxidative stress. At
stopover sites, they feed on sugary fruits and
nectar to replenish fat stores and often simul-
taneously consume dietary antioxidants (5).
They also likely use assimilated sugars (food
sugars transported into the blood for use/
storage) to repair oxidative damage. Because
the biosynthesis of lipids requires NADPH,
the PPP likely performs a dual function in
these migrants at stopover sites. Human ath-
letes who feed on carbohydrates during ex-
ercise have increased performance, although
the underlying mechanisms remain unclear
(6). One of these mechanisms may be one
that they share with hovering pollinators: re-
liance on reducing power provided by dietary
sugar and the PPP. j
REFERENCES AND NOTES
1. E. Levin et al ., Science 355, 733 (2017).
2. S. K. Po wers, M. J. Jackson, Physiol. Rev. 88, 1243 (2008).
3. A. Stincone etal.,
Biol.Rev.90, 927 (2015).
4. D. M. Townsend et al ., Biomed. Pharmacother .57, 145
5. M. M. Skripetal.,Ecol.Evol.5, 3198 (2015).
6. A.D.Karelis et al., Sports Med.40, 747(2010).
We thank S. McWilliams for useful comments. H. Sease
contributed to the drawings in the figure. M.E.D. was funded by
NADPH recycles GSSG
to GSH, an antioxidant
that helps to ameliorate
In the fed, resting moth,
the PPP generates CO2.
caused by intense
A hawkmoth (Manduca sexta) hovers
while using its long proboscis to reach
the nectar in a Datura flower.
How hawkmoths avoid oxidative damage
The high rates of oxygen production of hovering animals generate ROS that cause oxidative damage.
Hawkmoths avoid the buildup of ROS by using the ancient pentose phosphate pathway (PPP).