Phosphatidic Acid as a pH Biosensor

Byron's Comments:

New insights on what regulates body pH.

Study Title:

Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Study Abstract:

Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate headgroup. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.

From press release:

Acidity (pH) in cells of baker’s yeast, Saccharomyces cerevisiae, regulate the synthesis of cell membranes by controlling the production of enzymes that synthesize membranes. These are the findings of researchers at the University of British Columbia in Vancouver, Canada, in close collaboration with systems biologists at the University of Amsterdam (UvA). The results of this research have just been published in the journal Science. The elucidated mechanism is so simple and universal that it is highly likely that it determines many processes in the cell in all forms of life.

The UvA scientists, led by Dr. Gertien Smits, have been studying the regulation of acidity in the cell. They have developed a method to accurately and quickly measure the pH in live, growing cells. Understanding this process is important because small changes in acidity could have major consequences for the functioning of a living cell. The acidity in the cell is determined by the number of protons. These small charged particles can easily bind to many molecules in living cells, such as proteins, DNA, lipids and metabolites, or just as easily detach from the molecules. Whether or not a proton binds affects the charge properties of these molecules, and hence their properties. Given that this can occur for so many molecules in life, small changes may have big consequences. However, precisely because the process is so sensitive, until now it was very difficult to properly understand the dynamics of the acidity and the effects of their changes.

Acidity as regulator

The Vancouver researchers have focused their research on the regulation of membrane synthesis. They have studied the regulation of a central regulatory protein, Opi1, herein. This protein in the nucleus can inhibit the production of a number of membrane synthesis proteins, but is usually kept outside the nucleus because it binds to a specific lipid for membranes, phosphatidic acid. Together, the research groups from Vancouver and Amsterdam have come up with the hypothesis that the acidity in the cell can sometimes play an important role in regulating Opi1, as the physical and chemical properties of phosphatidic acid are such that the charge can be greatly determined by the proton concentration.

From signal to signal

Through the combination of measurements of pH and determination of the localization of Opi1 in living yeast cells, the correlation between the two has become increasingly apparent. Ultimately, the researchers have managed to show that the interaction between the protein and lipid is directly determined by the acidity in a very small pH range in the cell. This is precisely the range in which the acidity in living yeast cells varies depending on the presence of nutrients. In this way a signal for the presence of food can be converted into a signal to make membranes, and thereby grow. Based on the results the researchers suggest that it is highly probable that the pH determines more regulatory mechanisms and interactions in the cell.

The new findings have important implications for understanding human metabolism and disease because lipid structure and function are very similar amongst all organisms. Further work is needed to explore the implications of this discovery for other areas, such as tumor progression – because both phosphatidic acid and pH play important roles in this process – and brain research – because brain cells dynamically change their cellular pH, implying they, too, use a pH sensor.

Study Information:

Barry P. Young, John J. H. Shin, Rick Orij, Jesse T. Chao, Shu Chen Li, Xue Li Guan, Anthony Khong, Eric Jan, Markus R. Wenk, William A. Prinz, Gertien J. Smits, and Christopher J. R. Loewen. Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism Science 2010 August Vol. 329. no. 5995, pp. 1085 - 1088.
University of British Columbia in Vancouver, Canada.

Related Entries: Cinnamon Provides Impressive Benefits for Blood Sugar, Heart Health, Inflammation and More
Gastric Bypass Nutritional Consequences
Toxic Mineral Linked with Bowel Inflammation, Mitochondrial Damage, and Alzheimer’s
Magnesium and Vitamin B1 - Team Players Needed for Brain, Muscles, Metabolism, and More
Vitamin B1 / Thiamin - Are you getting enough?
H. Pylori and Autoimmune Link
Common Medications That Rob the Body of Nutrients
The Many Faces of Gluten Intolerance
Supplement Quality - Are You Getting What’s On the Label?
Statin Drugs Cause Atherosclerosis and Heart Failure
Heart Disease and Depression: A Two Way Street
Broken Heart Syndrome
Ten Things that Interfere with Thyroid Function
Vaccine Injury with Chronic Fatigue Syndrome and Fibromyalgia
Bone Loss Caused by Thyroid Meds and Other Drugs
Five Key Tips for a Healthy 2015
Top Health Stories of 2014
Combat the Winter Blues
Carnosine – Amazing Benefits for Athletes, Heart, Brain, Eyes, and Diabetes
ADT Prostate Cancer Therapy Does More Harm Than Good
Musicians: A Note on Taking Care of the Body
Infections Linked to Autoimmune Thyroid Problems
Noni: Tropical Super Fruit – Powerful Support for the Immune System, Brain, Bones, and more
Enlarged Adenoids Linked with Food Allergies
Combat Ear Infections and Congestion Naturally
Glaucoma: Protecting Against a Silent, Devastating Disorder
Protect and Energize Your Immune System
GMOs, Roundup, and Sunscreen Linked with Diminished Brain Resiliency
Signs of Concussions and Mild Traumatic Brain Injury
Sleep – Molecular Clean Up Time for the Brain
Artificial Sweeteners Provoke High Risk for Diabetes
Hypothyroidism, Brain Stress, and Season Changes
Alcohol, Adolescents, and Young Adults – A Neurological Disaster Waiting to Happen
GABA: Managing Brain Stimulation, Anxiety, and Other Consequences
Brain Fatigue: Fundamental Solutions
Brain Fatigue 101
Astonishing Benefits of Cranberries
Summer Heat Stress – More Than Just Dehydration
Chronic Active Epstein Barr Virus: Additional Tools for the Battle
Pine Nut Oil Reduces Inflammation, Clotting Risk, and Fatty Liver Congestion
New Findings with Epstein Barr Virus: The Sleeping Giant
Type 1 Diabetes: Risk Factor Alert
Disrupted Gut Clocks Linked with IBS, GERD, Obesity, and Other GI Concerns
Body Clocks and Weight Management – It’s All About Timing
Saturated Fat Myth – Debunked Again
Powerful Nutrition for Common Chemical Exposures
Endocrine Disruptor Compounds and Natural Solutions
Endocrine Disruptor Compounds and Your Hormones
Low Blood Pressure Linked with Brain Atrophy
Vitamin K, Leptin, AGEs, and Arthritis
Advanced Solutions for Osteoarthritis
Osteoarthritis: Good Oils versus Bad Oils and Inflammation
High Levels of Omega 6 Fatty Acids Found in Bones of Osteoarthritis Patients Worsens Joint Breakdown
Lipoic Acid Protects the Heart and Immune System from Acute Emotional Stress
Whiplash, Thyroid, and Adrenals
Brain Inflammation Now Documented in Chronic Fatigue Syndrome
Brain Protective Effects of Proathocyanidins
Nutrient Highlight: Discover the Best Form of Folate
Lutein and Zeaxanthin Offset Gene Weaknesses that Cause Macular Degeneration
Lycopene Builds Its Anti-Prostate Cancer Case
Carotenes Improve the Quality of Semen
Vitamin B12 as Methylcobalamin Repairs Nerves & Lowers Pain
Folic Acid Activates Neural Stem Cells for Brain Rejuvenation
Chromium Improves Insulin Function & Reduces Binge Eating
How Fiber and Niacin Protect Against Colon Inflammation and Cancer
Berries Have Anti-Aging Impact on Immune System
Strawberries Reduce Cardiovascular Risk
Friendly Flora Improves Fatty Liver Disease
Flavonoid Intake Improves Cardio Health in At-Risk Men
Polyphenols and Essential Fatty Acids Reduce Cardio Risk in Overweight People
Vitamin C Reduces the Risk for Hemorrhagic Stroke
Testosterone Therapy Increases Heart Attack Risk
Magnesium Intake Linked to Lower Cardiovascular Inflammation
Q10 Boosts Energy, Nerves, Muscles & Metabolism
Coenzyme Q10 Remarkably Improves Circulation
Tyrosine Helps Maintain Mental Ability Under Stress
Green Tea Extract Lowers Blood Pressure, Cholesterol, Blood Sugar & Inflammation
Poor Flexibility is a Sign of Stiff Arteries
A Sluggish Lymph System Causes Snoring & Sleep Apnea
DHA is Vital to Cardiovascular Wellness
Magnesium Supplements Lower Blood Pressure, Prevent Calcification
Magnesium for the Prevention of Heart Disease
Pomegranate Protects HDL Cholesterol from Damage
Pomegranate Blocks Flu Replication
Tocotrienols:  Twenty Years of Dazzling Cardiovascular and Cancer Research
Is Resveratrol the Fountain of Youth?
Grape Seed Extract Lowers Blood Pressure
Scientists Tout Resveratrol as a Primary Nutrient for Cardio Health
Leptin, Thyroid, and Weight Loss
Excess Appetite Causes Abdominal Fat

Most Popular News:

Connect with Wellness Resources:

Connect on Facebook Follow us on Twitter Wellness Resources on Pinterest Wellness Resources YouTube Channel Get RSS News Feeds
Thyroid and Metabolism