A 51-year old woman was admitted to hospital because of sharp abdominal pain, vo

Question

A 51-year old woman was admitted to hospital because of sharp abdominal pain, vomiting, and fever. The patient’s history was unremarkable; she had not abused alcohol and had not received any long-term treatment. A physical exam revealed that the patient was malnourished, probably due to low economic status and abdominal symptoms. Blood tests revealed anemia, iron deficiency, elevated white blood cell count, and low concentrations of total protein and albumin. During exploratory laparotomy, a fragment of necrotic cecum was identified and removed. The patient received five units of erythrocytes to treat anemia. The patient also received albumin and a high-protein diet. After 19 days of hospitalization, the woman’s clinical condition improved enough for her to be discharged and convalesce at home. After five days, the patient was re-admitted to the surgical ward with a fever and signs of wound infection. The patient was given antibiotics, and gradually her fever reduced and her wound healed. Although her general condition improved, she developed apathy, loss of appetite, and reluctance to engage in physical rehabilitation. Neurology and psychiatry services were consulted and found normal consciousness but slow mental reactions and reduced movement. The patient had difficulty retracing a sequence of events and memorizing, and displayed disorientation with respect to time and place, slow pupil reaction to a light stimulus, and ataxia in all four limbs with near immobilization in the lower limbs. A CT scan of her brain revealed no abnormalities. Suspecting Wernicke-Korsakoff syndrome, the patient was moved to a neurological ward and her blood was tested for vitamin B1 levels, which were 9 µg/L (normal range is 33-110 µg/L). Vitamin B1 (thiamine) is a component of TPP in pyruvate dehydrogenase (PDH) complex.

1.           Summarize the overall goal of the PDH complex.

2.           Could vitamin B1 deficiency affect functioning of the PDH complex? Why or why not?

3.           Summarize the overall goal of the citric acid cycle.

4.           Could vitamin B1 deficiency affect functioning of the citric acid cycle? Why or why not?

5.           Given that neurons can only use glucose as a source for acetyl CoA, postulate as to why this patient experienced primarily neurological symptoms.

Explanation / Answer

1). Summarize the overall goal of the PDH complex.

The overall goal of pyruvate dehydrogenase complex (PDH) is the formation of acetyl-CoA. The binding of pyruvate to the E1 subunit and its decarboxylation, the binding of acyl product to the lipoamide coenzyme through a thioester bond occur simultaneously. The acyl group is transferred to the E2 subunit along with the lipoamide arm, and then transferred to Coenzyme A, it results in the formation of acyl-CoA.

2). Could vitamin B1 deficiency affect the functioning of the PDH complex? Why or why not?

Yes, the vitamin B1 deficiency affects the PDH functioning, because the pyruvate dehydrogenase (E1) consists of pyruvate and thiamine pyrophosphate (TPP).

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