Vitamin B1, B6 and B12 play a vital role to keep the nervous system healthy. In diabetic neuropathy, supplementation with these vitamins prevents the complications.
Action Potential:
Like all the cells, neurons also have a potential at rest which is called Resting Membrane Potential and it is -70 millivolts. When sodium diffuses in through the sodium leaky channels the potential s drops and it is called Depolarization. When the potential reaches -55 millivolts, the threshold, all the sodium channels are opened and there is rapid depolarization which is also called Action potential. All the information either sensory or motor goes from periphery to brain and from brain back to periphery in the form of action potential. This action potential jumps from Node of Ranvier to Node of Ranvier and it is called Saltatory Conduction. It is fast conduction. It occurs from Node to Node. So, we need nodes. For the nodes we need myelin sheath and myelin sheath is made up of Schwan Cells which are living cells and need blood for oxygen and nutrients to remain alive. In Diabetes, due to microangiopathy, the blood flow is compromised, and the myelin sheath is damage resulting in Neuropathy. These ion channels are present throughout the axons of the neuron but are insulated by the myelin sheath and are only available, where there is no myelin sheath, that is Node of Ranvier.
Thiamine – B1:
Thiamine or Vitamin B1 is co-enzyme for three enzymes, Pyruvate Dehydrogenase in glycolytic pathway, Transketolase in HMP Shunt or Monophosphate Shunt and Alpha-ketoglutarate Dehydrogenase in the TCA Cycle. Since Thiamine is a water-soluble vitamin, it is filtered by the kidney and is excreted as urine. From the urine the Thiamine Transporter 1 and 2 reabsorbs it from the proximal and distal convoluted tubules and is recycled. In Diabetic Nephropathy, these Thiamine Transporter 1 and 2 are down regulated and therefore Thiamin or Vitamin B1 is flushed out causing its deficiency in Diabetic patients and creates a need to replace it.
Pyridoxine – B6:
Vitamin B6 exists in three form, Pyridoxine, Pyridoxamine and Pyridoxal Phosphate. Active form is Pyridoxal Phosphate. When it is metabolized, it is
excreted as a Pyridoxic Acid in urine. Dr. Naila Rabbani and Prof. Thorn’s study ISIS compared the level of Vitamin B6 in the blood and urine of both Diabetics and Controls and found that in diabetics blood, Vitamin B6, Pyridoxal Phosphate was low but its end-product that is Pyridoxic Acid was high in urine. It proves that in Diabetics, there is degradation of Vitamin B6 and therefore there is a need to replace Vitamin B6 in them.
Cobalamin – Vitamin B12:
Vitamin B12 exists in 6 form, Methyl cobalamin, Adenosyl cobalamin, Cyanocobalamin, Hydroxocobalamin, Aqua cobalamin and Nitritinocobalamin. Its Active form in humans are Methyl Cobalamin and Adenosyl cobalamin while Cyanocobalamin is the most stable form.
Methyl cobalamin is the co-enzyme of two enzymes, namely Methyl tetrahydrofolate, which is the enzyme of Folic Acid Cycle and the Methionine Synthetase, which is the enzyme of Homocystein Cycle.
Methyl group or One Carbon is transferred from the folic acid cycle to the Homocystein Cycle, which is taken up by the Homocystein and is converted to the Methionine. From Homocystein, one carbon is transferred to the DNA, RNA & Proteins and methylate’s them (Methylation of DNA & RNA is required for Gene Expression so that it can be copied i.e., Replication). Our objective is to lower the levels of Homocystein as it is a Sulphur containing Amino Acid, that damages the nerves as well as blood vessels resulting in Neuropathy and Angiopathy. By giving Vitamin B12 – Methyl cobalamin, we can lower down the levels of Homocystein and prevents the Neuropathy and Angiopathy.
Adenosyl cobalamin has a role in the conversion of Melonyl CoA. When fats are metabolized, they are broken down into even chain and odd chain free fatty acids. Brake down of Free Fatty Acid is called Beta-Oxidation. Beta-Oxidation of Even chain results in the formation of two acetyl CoA, which goes into the Citric Acid Cycle. But when an Odd Chain Free Fatty Acid is broken, one Acetyl CoA and one Melonyl CoA is formed. Acetyl CoA goes into the Citric Acid Cycle in the Mitochondria, but melony CoA cannot diffuse into the mitochondria as it is not fat soluble. It must be converted into the Methyl-Melonyl CoA for which the enzyme is Methyl-Melonyl CoA Dismutase and its co-enzyme is Adenosyl Cobalamin. In diabetic there is increase resistance to the intercellular vitamin B12 Function, therefore malonyl CoA is not converted to Methyl-Melonyl CoA and instead converted into Methylmalonic Acid (MMA), which accumulates around the nerves damaging them resulting in Neuropathy. By giving Vitamin B12, we can prevent this nerve injury.
#diabetes
#neuropathy
#vitaminB
