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In: Biology

The lack of vitamin B1 (thiamine) can lead to a disease called beriberi, which manifests as...

The lack of vitamin B1 (thiamine) can lead to a disease called beriberi, which manifests as cardiac and neurologic symptoms alongside elevated levels of pyruvate and α-ketoglutarate in the blood. Explain how a deficiency of this vitamin causes the increased levels of the two components.       

Solutions

Expert Solution

Thiamine (Vitamin B1) act through its coenzyme form i.e. Thiamine Pyrophosphate (TPP) which is mostly involved in carbohydrate metabolism.

Functions of TPP:

1. The multienzyme complex pyruvate dehydrogenase that catalyses (oxidative decarboxylation) the breakdown of pyruvate into Acetyl CoA and CO2 requires TPP as on of the coenzyme. Hence in the deficiency of thiamine, reaction will not occur and hence the concentration of pyruvate increases.

2. Oxidative decarboxylation of Alpha ketoglutarate to Succinyl CoA in KREBS CYCLE is catalyzed by alpha ketoglutarate dehydrogenase which requires 5 coenzymes to function: TPP, NAD, FAD, CoA, Lipoamide. When TPP decreases reaction cannot continue further, hence the concentration of alpha ketoglutarate gets increased.

In Thiamine deficiency glucose metabolism is impaired. This affects the central nervous system since it is dependent on glucose for its energy needs. Nerve impulse conduction is adversely affected. There is accumulation of pyruvate causing vasodilation and increased cardiac output. Prolonged thiamine deficiency causes a condition called beriberi.  

Wet beriberi: because of impaired energy metabolism in the myocardium, peripheral vasodilation occurs causing a high output state, biventricular heart failure with pulmonary congestion and retention of sodium and water leading to edema. Death occurs due to heart failure.

Dry beriberi: in this type the nervous system is affected. It presents with progressive muscle wasting, peripheral neuropathy of the motor and the sensory systems with reduced reflexes. Walking becomes difficult and patient feels difficulty in rising from a squatting position.


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