Question

Investigating blood pH

In consultation with the medical examiner, you decide to run more specific blood tests to determine the cause of the subject's acidosis.
First, you assess the blood levels of ketone bodies, using acetoacetate as a marker. This test shows a detectable level of acetoacetate. However, the level is not high enough to indicate diabetic ketoacidosis.
Next, you assess his arterial blood gas results, which were analyzed before he arrested.
pO2 = 88 mmHg (normal range: 75–100 mmHg)
pCO2 = 41 mmHg (normal range: 35–45 mmHg)
You note that the partial pressures of O2O2 and CO2CO2 in the blood were both in the normal range.
Finally, you review his serum concentrations of lactate and pyruvate, which were also measured before he arrested.
[lactate] = 5.5 meq/L (normal range: 0.4–2.2 meq/L)
[pyruvate] = 0.32 meq/L (normal range: 0–0.11 meq/L)
You note that the levels of both pyruvate and lacate in the blood were elevated. You also find high levels of alanine, α‑ketoglutarate, and glutamate. The high alanine level is most likely due to the high pyruvate level, and the high glutamate level is most likely due to the high α‑ketoglutarate level.
The man in this case appears to have experienced simultaneous loss of activity of the PDH complex and the α‑ketoglutarate dehydrogenase complex.
What would be the mostly likely cause of this simultaneous loss of enzymatic activity in this case?
1. a lack of insulin activity due to diabetes
2. hormonal down‑regulation of the expression of both enzymes
3. genetic polymorphisms in the genes encoding both enzymes since birth
4. a vitamin deficiency
5. genetic mutations affecting both enzymes that occured recently
6. deficient oxygen transport that results in tissue hypoxia
7. acute alcohol intoxication
8. dehydration

Answer 1

The most likely cause of the simultaneous loss of enzymatic activity in this case is genetic mutations affecting both enzymes that occurred recently.

Step-by-step explanation:

The most likely cause of the simultaneous loss of enzymatic activity in this case is genetic mutations affecting both enzymes that occurred recently. This is supported by the fact that the levels of both pyruvate and lactate in the blood were elevated, along with high levels of alanine, α‑ketoglutarate, and glutamate. The high alanine level is most likely due to the high pyruvate level, and the high glutamate level is most likely due to the high α‑ketoglutarate level.

Answer 2

A vitamin deficiency is the most probable cause of simultaneous loss of activity in both the PDH complex and the α-ketoglutarate dehydrogenase complex, as these enzyme complexes depend on vitamins as co-factors.

Step-by-step explanation:

When considering a simultaneous loss of activity of the PDH complex and the α-ketoglutarate dehydrogenase complex, the presence of normal partial pressures of O2 and CO2, along with elevated levels of lactate, pyruvate, alanine, α-ketoglutarate, and glutamate, points to a specific cause that is not related to diabetes mellitus or an issue with oxygen transport, since diabetic ketoacidosis and tissue hypoxia can be ruled out.

The most likely cause of this loss of enzymatic activity is a vitamin deficiency. Both the PDH complex and the α-ketoglutarate dehydrogenase are multi-enzyme complexes that require certain vitamins as co-factors, such as thiamine (vitamin B1), lipoic acid, niacin (vitamin B3), pantothenic acid (vitamin B5), and riboflavin (vitamin B2). A deficiency in one or more of these vitamins could impair the functioning of both complexes.