Glucose thiamin deficiency

In the 1930s, Peters and co-workers showed that thiamine deficiency in pigeons resulted in the accumulation of lactate in the brainstem [ 15]. Furthermore, they showed that the addition of small quantities of crystalline thiamine to the isolated brainstem tissue from thiamine-deficient birds in vitro resulted in normalization of lactate levels. These findings led to the formulation of the concept of the biochemical lesion in thiamine deficiency. Subsequent studies showed that the enzyme defect responsible for the biochemical lesion was a-KGDH rather than pyruvate dehydrogenase (PHDC), as had previously been presumed. a-KGDH and PHDC are major thiamine diphosphate (TDP)-dependent enzymes involved in brain glucose oxidation (Fig. 34-4). 

TAs one might predict, mutations in the genes for the subunits of the PDH complex, or a dietaiy thiamine deficiency, can have severe consequences. Thiamine-deficient animals are unable to oxidize pyruvate normally. This is of particular importance to the brain, which usually obtains all its energy from the aerobic oxidation of glucose in a pathway that necessarily includes the oxidation of pyruvate. Beriberi, a disease that results from thiamine deficiency, is characterized by loss of neural function. This disease occurs primarily in populations that rely on a diet consisting mainly of white (polished) rice, which lacks the hulls in which most of the thiamine of rice is found. People who habitually consume large amounts of alcohol can also develop thiamine deficiency, because much of their dietaiy intake consists of the vitamin-free empty calories of distilled spirits. An elevated level of pyruvate in the blood is often an indicator of defects in pyruvate oxidation due to one of these causes. ... 

Til. Role of the Vitamin Thiamine People with beriberi, a disease caused by thiamine deficiency, have elevated levels of blood pyruvate and a-ketoglutarate, especially after consuming a meal rich in glucose. How are these effects related to a deficiency of thiamine ... 

In the second case, the authors were unsure if the associated graft failure was due to the acute metabolic acidosis or thiamine deficiency, since the absence of thiamine in the diet leads to poor glucose oxidation, resulting in accumulation of lactic acid and metabolic acidosis, which is refractory to any treatment except thiamine supplementation. 

The severity of the symptoms of thiamin deficiency has been associated with energy intake. The consumption of large doses of glucose has been foimd to induce an unusual rise in plasma pyruvate and lactate, as well as neurological symptoms, in thiamin deficient humans. Because of this association, the thiamin requirement is sometimes expressed on a per energy intake basis. 

We found that the addition of 10% sorbitol did not merely prevent the development of thiamine deficiency, but allowed the animals to grow far better than on the (iarbohydrate-free diet. Moreover, we could add large amounts of glucose to the sorbitol-containing diet and the animals continued to thrive in the complete absence of dietary thiamine. In addition, we showed that this vitamin-sparing effect was not confined to thiamine, since the sorbitol allowed the nits to thrive on diets with none of the vitamins of the B group. 

Nerve tissue is mainly dependent for ATP production on glucose metabolism via glycolysis to produce acetyl CoA by the PDH reaction for oxidation in Krebs cycle. Since thiamin is essential for PDH activity, thiamin deficiency, which can occur in malnourished alcoholics, results in PDH dysfunction and an energy deficit in nerve tissue. This causes hyperlactataemia and neuropathy, which can progress to Wernicke s encephalopathy and Korsakoff s psychosis (Chapter 53). 

ThDP plays a crucial role as coenzyme for several enzymes and enzyme complexes such as transketolase (EC 2.2.1.1) and the enzyme complexes pyruvate (EC 1.2.4.1) and 2-oxoglutarate (EC 1.2.4.2) dehydrogenases, present in nearly all organisms. They play important catabolic roles and are key actors in cell energy metabolism (Figure 5.1). Reduced activity of these enzymes as a consequence of thiamin deficiency results in decreased glucose oxidation. As the brain heavily relies on oxidative metabolism, it is more severely affected by thiamin deficiency than other organs. 

Altered glucose metabolism is a key feature of thiamine deficiency and WE. 

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