1 THE VALUE AND PRICE OF MEN’S ADDICTION TO IRON On chronic iron deficiency and novel treatments relevant to corona days 2 and Chaim Hershko 1 Ioav Cabantchik The Hebrew University of Jerusalem Despite major advances in Biology and Medicine and the increasing awareness of nutrition to human health and wellness, anemia remains a major public health problem. About half of the millions of anemia cases worldwide are associated with iron deficiency (ID) that manifest initially as physical fatigue and progressively leads to major dysfunctions with serious clinical outcomes. A major source of the problem is inadequate (ineffective or insufficient) food sources, that exacerbates during worldwide crisis, as in the present corona pandemics. Those affected are primarily children, young girls, pregnant women and the elder population. But among those most afflicted are individuals with chronic inflammatory disorders, as found in inflammatory bowel disorders IBD (Crohn’s, ulcerative colitis, etc), in celiac, rheumatoid arthritis, most types of cancer and especially in infections (bacterial, viral or parasitic). How does one clinically cope with chronic ID in normal times and most importantly during periods of crisis, when clinical services relevant to the ID population are limited or inaccessible? Where and how is the essential role of iron manifested in life? The best known need for iron is in respiration and the most commonly known indicator is hemoglobin, whose role in blood is the capture of oxygen as red blood cells pass through capillaries in the lung and transfer it to all tissues. More than 75% of body iron is associated with the protein hemoglobin, 5% with muscle myoglobin, 15% with the liver and spleen (primarily stored in ferritin molecules) and only 5% in the rest tissues, mostly as heme and iron-sulfur proteins. These proteins confer to the iron a wide spectrum of chemical activities that are expressed in about 30% of all cell functions, such as: cell respiration, oxygen sensing, synthesis of DNA bases, of lipids, neurotransmitters in the excitable tissues in the brain and heart, etc. Among the vital iron-based functions we identify many that have been preserved throughout millions of years of evolution, most likely from life’s onset in the anaerobic planet. However, with the advent of atmospheric oxygen, the available iron oxidized and precipitated as insoluble oxides, posing living systems with the major challenge of acquisition of the life-essential metal. The same challenge is faced by all higher organisms that for their survival in an aerobic world, they need to extract the metal from nutritional sources, absorb it and handle it cautiously by unique means. That is because ionic iron is catalytically active and in the presence of oxygen it is capable of generating noxious reactive oxygen species (ROS) that can damage cell components. The dual character of iron, essential but risky, pose all living cells with the double challenge of controlling the iron levels so as to meet cells metabolic demands and concurrently protecting cell components from potential hazardous iron-driven ROS formation. Although key players in cell antioxidant defense are cell enzymes that counteract ROS 1 contact Dr. Yoav Cabantchik, Professor (Emeritus) A&M Della Pergola Chair in Life Sciences, Hebrew University, Jerusalem, ioav.caban@mail.huji.ac.il https://www.bio.huji.ac.il/en/search/node/cabantchik 2 Dr. Chaim Hershko, Professor (Emeritus) Internal Medicine, Hadassah Medical School,Hebrew University, Jerusalem and Shaare Zedek Medical Center, Jerusalem hershkoc@netvision.net.il