Cancer lactate dehydrogenase

The elevations of the germ cell tumour markers P-human chorionic gonadotrophin (P-HCG), a-fetoprotein (AFP) and lactate dehydrogenase (LDH) further support the working diagnosis of testicular cancer. The levels of P-HCG and AFP in particular are negligible in males in normal circumstances, but they are raised in patients with testicular cancers as the tumours secrete these substances in large quantities. 

Latency period The period of time between exposure to something that causes a disease and the onset of the health effect. Cancer caused by exposure to chemical substances may have a latency period of 5-40 years LDH Lactate dehydrogenase... 

A transient, moderate, and reversible rise in leukocyte alkaline phosphatase, lactate dehydrogenase (LDH) and serum uric acid concentrations is usually observed in cancer patients receiving supportive treatment with GM-CSF or G-CSF. Serum LDH increased from 37 to 85% and there was a linear relation between increased leukocyte production and the rise in serum LDH (32). Increases in serum LDH activity should therefore not be interpreted as indicative of disease progression, unless LDH activity remains high after growth factor withdrawal. 

Yamagata, M. Hasuda, K. Stamato, T. Tannock, I. F. The contribution of lactic acid to acidification of tumors studies of variant cells lacking lactate dehydrogenase. Br. J. Cancer 1998, 77, 1726-1731. 

An inhibitor for lactate dehydrogenase would block the formation of lactic acid or lactate, the main distinguishing feature of cancer cell metabolism. This would alternately favor the normal oxidation of pyruvic acid or pyruvate via the tricarbox-yhc acid cycle. As a quahlication, cancer cells also apparently undergo a degree of oxidative metabohsm, though the conversion to lactate or lactic acid occurs to a much greater extent. 

Thus, it may be concluded that perhaps the simplest way to inhibit cancer cell metabolism is merely to block the enzyme lactate dehydrogenase for the conversion of pyruvic acid or pyruvate to lactic acid or lactate. 

Furthermore, the latter conversion reaction, the hydrogen reduction of pyruvic acid to lactic acid, or pyruvate to lactate, would be the controlling step in the metabolism of cancer cells. It is catalyzed by the enzyme lactate dehydrogenase, as previously noted, and if an effective inhibitor or catalyst poison can be found that is selective to this particular step, it could concdvably suppress the metabolism of cancer cells. 

Based on in vivo experimental results reported, vitamin C can also be viewed as an inhibitor for the key enzymes involved in carbohydrate metabolism or glycolysis, including lactate dehydrogenase, which is involved in cancer cell metabolism (Hoffman, 1999, p. 395). The inference is that vitamin C is an anticancer agent, as advanced by Pauling and Hoffer. 

This statement is about cancer ceU metaboUsm, the main metabolic pathway of which is the conversion of glucose or glycogen to lactic acid or lactate rather than to carbon dioxide and water, as occurs in normal cells. Furthermore, the key enzyme for the conversion of glucose to lactic add is lactate dehydrogenase. Fortunately, a number of enzyme inhibitors for lactate dehydrogenase are known and can be viewed as potential anticancer agents, with others presumably in the offing. 

A mitigating factor is whether conversion is selective to yield lactic acid or lactate, as in cancer cells, or selective to yield carbon dioxide and water, as in normal cells. This depends on the absence or presence of, say, inhibitors for the enzyme lactic dehydrogenase, as set forth in Chapter 3. That is, absence of inhibitors for lactate dehydrogenase would favor cancer cell metabolism.)... 

It would be interesting to know whether there is any (say, epidemiologic) connection between malarial immunity and cancer immunity. Thus, many native inhabitants of the tropical areas fortunately develop immunity to malaria, which may or may not be related to the inhibition of the malarial enzyme lactate dehydrogenase or other critical malarial enzymes. 

In many instances, such as in cancer, it is important to analyze a single or very few cells rather than homogenizing the whole tissue. Small capillaries of 10pm in diameter have been used to study the level of some metabolites in single cells, e.g., catecholamines, 5-hydroxyindole acetic acid including the level of the enzyme lactate dehydrogenase. However, cell introduction into the capillary and lyses is not an easy task. Eurthermore, this analysis requires the use of very sensitive detection. 

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