Spectroscopic evidence for the unusual handedness of a mammalian lipid may advance our understanding of evolution

March 23, 2012
Figure 1: The backbone of the chemical structure of phospholipids in archaea is right-handed; in more complex organisms, it is left-handed. Credit: 2012 Peter Greimel

Phospholipids are the main constituents of the cellular membranes in all organisms, ranging from single-celled archaea to highly complex plants and mammals. According to conventional wisdom, the chemical backbone of phospholipids in archaea is ‘right-handed’, but left-handed in all other organisms (Fig. 1). The little-understood mammalian phospholipid bis(monoacylglycero)phosphate (BMP), however, is a possible exception to this rule. Peter Greimel, HuiHui Tan and their colleagues at the RIKEN Advanced Science Institute, Wako, have now obtained the first proof that BMP is indeed right-handed. 

BMP is found only in , and is a common—but minor—constituent of all animal tissues. The internal membranes of the waste treatment and recycling centers of cells—so-called late endosomes and lysosomes—have a higher proportion of BMP than any other animal membranes. This raised an intriguing question, explains Greimel: “How does BMP escape degradation inside these organelles, unlike all the other lipids and proteins?” This led to the [hypothesis] that BMP might actually be right-handed, allowing it to avoid attack by the organelle’s digestive enzymes that are only capable of recognizing, and therefore destroying, left-handed lipids. All previous attempts to confirm the suspected unusual handedness—or chirality—of BMP had hit problems.

The research team first synthesized all the possible variations of BMP. They then reacted these variations with the chiral shift reagent D-camphor. “The D-camphor induced a change in the spectroscopic behavior of each synthetic BMP analogue,” explains Greimel. This meant that the nuclear magnetic resonance (NMR)—a common spectroscopic technique—spectra of the BMP analogues were different enough to be distinguished from each other.

Next, the researchers isolated natural BMP from baby hamster kidney cells using standard techniques, then reacted it with D-camphor under very gentle conditions and analyzed it spectroscopically. They then compared the NMR spectra of the natural BMP derivative and the synthetic molecules. “Analysis of the spectroscopic data revealed that natural BMP is exclusively right-handed,” Greimel says. 

“Since BMP is right-handed, it means it most likely originated from the same common ancestor as ,” he explains. The research team now plans to identify the enzymes involved in the biosynthesis of BMP, with the hope that detailed knowledge of this biosynthetic pathway will eventually lead to a better understanding of how life evolved on Earth.

Additionally, Greimel says that “now we know the [chirality] of the molecule, we can think about synthesizing analogues in order to develop novel drugs, in this case to treat lysosomal storage diseases.”

Explore further: Protein maintains cross talk between cells that control hair growth

More information: Tan, H.-H., et al. Spectroscopic evidence for the unusual stereochemical configuration of an endosome-specific lipid. Angewandte Chemie International Edition 51, 533–535 (2012).

Related Stories

Tuning in on cellular communication in the fruit fly

February 18, 2009

In their ongoing study of the processes involved in embryonic development in fruit flies, researchers at WPI's Life Sciences and Bioengineering Center at Gateway Park have identified the function of a protein that sticks ...

New protein promotes embryonic brain formation

December 24, 2010

The various bone morphogenetic protein (BMP) signaling factors play an important role in early neural development in the vertebrate embryo. However, maturation of these tissues ultimately depends on the coordinated activity ...

Recommended for you

Brazilian wasp venom kills cancer cells by opening them up

September 1, 2015

The social wasp Polybia paulista protects itself against predators by producing venom known to contain a powerful cancer-fighting ingredient. A Biophysical Journal study published September 1 reveals exactly how the venom's ...

Naturally-occurring protein enables slower-melting ice cream

August 31, 2015

(Phys.org)—Scientists have developed a slower-melting ice cream—consider the advantages the next time a hot summer day turns your child's cone with its dream-like mound of orange, vanilla and lemon swirls with chocolate ...

Antibody-making bacteria promise drug development

August 31, 2015

Monoclonal antibodies, proteins that bind to and destroy foreign invaders in our bodies, routinely are used as therapeutic agents to fight a wide range of maladies including breast cancer, leukemia, asthma, arthritis, psoriasis, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.