As the endpoint of endocytosis, the lysosome also acts as a safeguard in preventing pathogens from being able to reach the cytoplasm before being degraded. Pathogens often hijack endocytotic pathways such as pinocytosis in order to gain entry into the cell. The lysosome prevents easy entry into the cell by hydrolyzing the biomolecules of pathogens necessary for their replication strategies; reduced Lysosomal activity results in an increase in viral infectivity, including HIV. In addition, AB5 toxins such as cholera hijack the endosomal pathway while evading lysosomal degradation.
Lysosomes are responsible for a group of genetically inherited disorders called lysosomal storage diseases (LSD). They are a type of inborn errors of metabolism caused by malfunction of one of the enzymes. The rate of incidence is estimated to be 1 in 5,000 live births, and the true figure expected to be higher as many cases are likely to be undiagnosed or misdiagnosed. The primary cause is deficiency of an acidic hydrolase (a hydrolase which functions best in acidic environments). Other conditions are due to defects in lysosomal membrane proteins that fail to transport the enzyme, non-enzymatic soluble lysosomal proteins. The initial effect of such disorders is accumulation of specific macromolecules or monomeric compounds inside the endosomal–autophagic–lysosomal system. This results in abnormal signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking, ultimately leading to pathogenetic disorders. The organs most affected are brain, viscera, bone and cartilage.
There is no direct medical treatment to cure LSDs. The most common LSD is Gaucher’s disease, which is due to deficiency of the enzyme glucocerebrosidase. Consequently, the enzyme substrate, the fatty acid glucosylceramide accumulates, particularly in white blood cells, which in turn affects spleen, liver, kidneys, lungs, brain and bone marrow. The disease is characterized by bruises, fatigue, anaemia, low blood platelets, osteoporosis, and enlargement of the liver and spleen.
Weak bases with lipophilic properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called “lysosomotropism” or “acid trapping”. The amount of accumulation of lysosomotropic compounds may be estimated using a cell-based mathematical model.
A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explains a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lifes; these properties have been found for drugs such as haloperidol, levomepromazine, and amantadine. However, high tissue concentrations and long elimination half-lives are explained also by lipophilicity and absorption of drugs to fatty tissue structures. Important lysosomal enzymes, such as acid sphingomyelinase, may be inhibited by lysosomally accumulated drugs. Such compounds are termed FIASMAs (functional inhibitor of acid sphingomyelinase) and include for example fluoxetine, sertraline, or amitriptyline.
Ambroxol is a lysosomotropic drug of clinical use to treat conditions of productive cough for its mucolytic action. Ambroxol triggers the exocytosis of lysosomes via neutralization of lysosomal pH and calcium release from acidic calcium stores. Presumably for this reason, Ambroxol was also found to improve cellular function in some disease of lysosomal origin such as Parkinson‘s or lysosomal storage disease.[33
Betaine HCL, helps stomach acid in breaking down food
Low hydrochloric acid is a potential cause of cancer and other immune and auto-immune conditions
Everyone, without exception, has cancer genes, “oncogenes,” circulating around the body. These cancer genes are normally kept in check by a healthy immune system, but in the case of cancer, the immune system can no longer suppress the cancer genes, which can then get out of control and multiply. The immune system responds by forming a tumor to contain the malignant cancer cells.
Chemotherapy may suppress cancer cells temporarily but also destroys the immune system, exposing the patient to a very wide range of additional diseases as well as additional types of cancer through immune-suppressed cancer gene expression.
If the “Th1” immune system is compromised or disabled, the “Th2” component of the immune system attempts to take over. Th2, not being equipped to function as Th1, perceives genuine body tissues as foreign invaders, attacking them as it would a bacterium or virus. Th1 suppression is also a root cause of auto-immune diseases such as allergies, celiac disease and arthritis.
How betaine HCl supplementation can bring valuable health benefits
Betaine hydrochloride (betaine HCl) increases the concentration of hydrochloric acid in the stomach relative to how much is taken before meals. This enables the stomach to much more completely dissolve and process foods right down to base nutrients, as well as produce methyl groups, an important element in preventing cancer and other diseases.
Taking betaine HCl before meals helps the stomach make optimum use of all dietary nutrients, also optimizing the immune system gut flora, without which, even with a healthy diet, many diseases including cancer can arise and propagate.
Note to vegetarians and vegans: Avoid betaine hydrochloride supplements that also contain pepsin, extracted from pig stomachs.