Dr. al-Khalidi's scientific research work focused on the metabolism of 2 key biomolecules: Purines and Lipids*.
His earliest works from the late 1950's involved experimentation in order to learn how to detect and quantify small molecules of interest, such as nucleotides and thus purines – base components of DNA. Next, Dr. al-Khalidi studied the structure of purine derivatives and how they behaved in response to stress – be it exercise or a complex disease process.
· Xanthine oxidase is an enzyme that breaks down xanthine (a purine) into uric acid, producing potentially harmful reactive oxygen species in the process. Dr. al-Khalidi investigated this protein as a marker of acute liver injury. He also described the species distribution of xanthine oxidase, and looked into hereditary conditions where accumulation of uric acid caused stone formation in the urinary tract.
· Similarly, serum guanase is an enzyme that breaks down guanine (another purine). It has been looked into as a screening tool for liver injury, and Dr. al-Khalidi took this further by investigating its usefulness in detecting diseases of the kidney. A method to determine guanase levels in finger-tip blood (the same way we monitor blood sugar today) was also described by Dr. al-Khalidi, and it was observed that low guanase levels correlated with a BUN (blood urea nitrogen) elevation in a variety of studied kidney diseases.
· Adenosine deaminase (ADA) is another enzyme involved in purine metabolism, and ADA Deficiency is a genetic (autosomal recessive) metabolic disorder that causes immunodeficiency. In fact, ADA deficiency is the second most common cause of severe combined immunodeficiency (SCID, aka “bubble boy disease”) – accounting for ~15% of all cases. Here, Dr. al-Khalidi worked to develop a sensitive biochemical assay for adenosine deaminase. It would detect and quantify ADA in a manner 1000x more sensitive than a spectrophotometric assay, and would be suitable for measurement of ADA in opaque solutions. It was concluded that in families with children suffering of SCID and ADA deficiencies, the assay would allow easy identification of the carrier state.
Early research in the 1960's helped Dr. al-Khalidi shed light on pieces of the cholesterol uptake mechanism. This led to a series of works on similar topics, involving the potential use of 14C-phenylacetic oil as a fat absorption test to better study the process in patients with malabsorption/maldigestion. Another theme explored the metabolism of acetoin and diacetyl (components of the buttery flavor and odor of foods) by the liver.
In the 1970’s, Dr. Khalidi devised a sensitive test to detect malononitrile and its derivatives. These are components of CS gas, an irritant agent sometimes used by the military and law enforcement in various parts of the world. The test Dr. al-Khalidi used could both quantify malononitrile levels and be adapted into a field paper-strip test. Additional research in the same period allowed Dr. al-Khalidi to purify and characterize human lymphocyte mitogenic factor (LMF), a protein that stimulates immune cell activity.
From an understanding of the implications of purine metabolism on human health to the development of a novel technique in aesthetic expression, Dr. al-Khalidi's tireless efforts have contributed volumes to the scientific and artistic repertoire.
* The background research and text on this page was prepared with thanks to Raji Naamani.