Nav: Home

The molecules that energize babies' hearts

June 14, 2018

A metabolic process that provides heart muscle with energy fails to mature in newborns with thickened heart walls, according to a Japan-Canada research team.

Hokkaido University cardiologist Arata Fukushima, along with a team of University of Alberta scientists led by Gary Lopaschuk, examined the heart tissue of 84 newborns who had undergone surgery for congenital heart disease. Many patients with the disease develop thickened heart walls, or hypertrophy, which can lead to fatal heart failure even after the surgery.

Before birth, cardiac muscle cells use energy generated by breaking down glucose. Immediately after birth, they rapidly switch to breaking down fatty acids. This switch is hindered in hypertrophied newborn hearts. Fukushima and his team wanted to investigate how this happens at the molecular level.

In the study, published in The Journal of Clinical Investigation Insight, the team compared the biopsy samples taken from normal and thickened right ventricular walls. They found that two enzymes involved in fatty acid break down, called LCAD and βHAD, were 'hyperacetylated' in non-hypertrophied right ventricles. This means that large amounts of acetyl groups were added to the enzyme proteins, increasing their activity levels. This, in turn, led to increased fatty acid metabolism.

In hypertrophied hearts, these two enzymes were not hyperacetylated, leading to reduced fatty acid metabolism in these newborns. The team detected reduced activity of an acetylation promoting gene, called gcn5l1, in hypertrophied hearts.

When the team experimented on cultured hypertrophy-like cardiac muscle cells, they found that turning off the gcn5l1 gene led to decreased acetylation of LCAD and βHAD, and a reduced fatty acid oxidation in the cells. Moreover, the cells lacking gcn5l1 formed thicker muscle fibers comparing to normal cells.

"Our findings show that acetylation of metabolic enzymes plays an important role in controlling the dramatic changes in energy metabolism that occur in newborn hearts immediately after birth," says Arata Fukushima. "The findings also show how hypertrophy can perturb this process by delaying the maturation of fatty acid metabolism, which compromises the ability of the newborn heart to generate energy. Developing drugs that enhance acetylation of the metabolic enzymes could help treat patients with hypertrophy."
-end-


Hokkaido University

Related Enzymes Articles:

Fungal enzymes team up to more efficiently break down cellulose
Cost-effectively breaking down bioenergy crops into sugars that can then be converted into fuel is a barrier to commercially producing sustainable biofuels.
How enzymes communicate
Freiburg scientists explain the cell mechanism that transforms electrical signals into chemical ones.
Pac-Man-like CRISPR enzymes have potential for disease diagnostics
UC Berkeley researchers have found 10 new variants of the Cas13a enzyme, the Pac-Man of the CRISPR world, that hold promise for disease diagnostics.
Hydrogen production: This is how green algae assemble their enzymes
Researchers at Ruhr-Universit├Ąt Bochum have analyzed how green algae manufacture complex components of a hydrogen-producing enzyme.
New studies unravel mysteries of how PARP enzymes work
A component of an enzyme family linked to DNA repair, stress responses, and cancer also plays a role in enhancing or inhibiting major cellular activities under physiological conditions, new research shows.
Understanding enzymes
A new tool can help researchers more accurately identify enzymes present in microbiomes and quantify their relative abundances.
Light powers new chemistry for old enzymes
Princeton researchers have developed a method that irradiates biological enzymes with light to expand their highly efficient and selective capacity for catalysis to new chemistry.
Research finds enzymes essential for DNA repair
Scientists at The Australian National University and Heidelberg University in Germany have found an essential component in the DNA repair process which could open the door to the development of new cancer drugs.
New step towards clean energy production from enzymes
Oxygen inhibits hydrogenases, a group of enzymes that are able to produce and split hydrogen.
Genetic diversity of enzymes alters metabolic individuality
Scientists from Tohoku University's Tohoku Medical Megabank Organization have published research about genetic diversity and metabolome in Scientific Reports.

Related Enzymes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...