Question

Questions 1. Thiamin deficiency was observed only in the Chinese community even though all three communities had the same staple (rice) diet. Explain. On packages of enriched rice sold in supermarkets, the rice preparation directions state that the 2. rice should not be washed before cooking. Explain. deficiency. Explain. Provide two plausible explanations for what might cause above normal levels of pyruvate in blood 3. Severe metabolic acidosis caused by high levels of lactate is often associated with thiamin 4. and urine. How can one determine which of the two explanations is correct? 5. Why does thiamin utilization increase among cancer patients? 6. A negative correlation exists between the need for thiamin and the amount of fat in the diet. Explain.

Answer 1

1. ANS: Thiamine (vitamin B1) is an essential for normal metabolic functioning of all cells, including the neurons and the cells in the brain. Thiamine is not synthesized in the human body, rather obtained after eating a diet rich in thiamine or following ingestion of vitamin supplements. The active form of Thiamine, thiamine pyrophosphate, is a cofactor that is essential for the activity of a number of enzymes involved in carbohydrate metabolism. In the given case study, only the Chinese migrant workers experienced a severe thiamine deficiency, while the native Malays and the Tamil population which was also consuming rice did not show symptoms of thiamine deficiency. The reason behind this selective thiamine deficiency in the Chinese community was the type of the rice that was consumed by those workers. The bran is the layer present between the inner white grain and outer hull of the rice grain. It accounts for only 6-8% of the total weight of the rice while providing 60% or so of nutrients of the rice kernel grain. The process of milling involves removal of the rice bran and polishing of the rice. The Malayan population was eating the rice that was hulled coarsely by the people themselves. The hulling process would have retained the bran that does not get washed off easily. As a result, the Malays did not have thiamine deficiency. The Tamil population consuming parboiled rice was also not deficient for thiamine,vitamin B1. The parboiled rice is steamed with the husk on prior to polishing. This steaming results in certain nutrients from the bran to get absorbed into the rice kernel/grain. This rice retains a good amount of thiamine even after polishing. However, polished white rice that is milled to remove the bran loses most of its thiamine content. In the industrialized world, this polished rice is often fortified with essential nutrients, vitamins and minerals that are spray coated on the polished grain. The rice consumed by the Chinese workers would not have been adequately fortified to provide thiamine resulting in a deficiency.

3. ANS: Thiamine pyrophosphate, which is the active form of thiamine, is a coenzyme for three physiologically critical enzymes including the pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase and transketolase. Pyruvate dehydrogenase is involved in lipid synthesis, gluconeogenesis and oxidation by the tricarboxylic acid cycle (TCA cycle). Transketolase catalyzes the rate limiting step involved in hexose monophosphate shunt. The breakdown of glucose to generate energy occurs in two general steps. In the first step glucose is broken down by glycolysis to form pyruvic acid or pyruvate. Pyruvate undergoes TCA or oxidative phosphorylation to generate energy. Pyruvate dehydrogenase is involved in TCA cycle and converts pyruvate to acetyl CoA. Thiamine pyrophosphate is the coenzyme associated with pyruvate dehydrogenase complex. Deficiency of vitamin results in inhibition of pyruvate dehydrogenase activity. This inhibition results in depletion of ATP, which is produced by the TCA cycle. In order to compensate for ATP loss, more energy is generated by glycolysis. This additional glycolysis results in the production of additional pyruvate that gets converted to lactate resulting in acidosis. Furthermore, glycolysis compensates for energy loss due to impaired TCA; however, it cannot bind to protons that are formed during ATP hydrolysis, resulting in increased proton concentration causing acidosis.

4. ANS: The two causes responsible for elevated pyruvate in the blood and the urine is a) genetic defect resulting in insufficient activity of the enzyme pyruvate dehydrogenase, which converts pyruvate to acetyl coA or b) deficiency of thiamine, which is involved as a coenzyme for the enzyme pyruvate dehydrogenase. Thiamine pyrophosphate is the active form of thiamine working as coenzyme. If a supplement of thiamine or vitamin can reverse the symptoms of acidosis, the condition existed due to vitamin B1 deficiency. If the intake of vitamin B1 does not reverse the acidosis, it is present due to some defect (genetic) in the functioning of or activity of the enzyme pyruvate dehydrogenase.

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