Most of it, if not all, creatures that live on this planet need energy to do everything and to be able to stay alive. We all know that we get our energy from foods we eat, and our body will digest it and absorb the nutrition we need like carbohydrate, fat, protein, etc. All these absorbed nutrition will then transported by blood to the whole body and through a mechanism called metabolism which then produces energy the body (cells) needs. I will not explain how those nutrition enter metabolism and then produces energy (I will explain it in under different post).
Pyruvate dehydrogenase complex (PDC) is a complex of enzymes in glucose metabolic pathway which is used to transform pyruvate to acetyl-CoA. It is composed of 3 enzymes which are called E1 [has four subunits, two alpha subunits (E1 alpha) and two beta subunits (E1 beta)], E2, and E3, and two proteins to control the PDC activity, a phosphatase (to activate) and a kinase (to inhibit). Each of these are necessary for the complex to work properly. The acetyl-CoA then enter citric acid cycle (Krebs cycle) under aerobic condition. This process happens in the mitochondria.
If the body or organ does not have ample supply of oxygen (anaerobic condition), the pyruvate that was produced from glycolysis process will then enter another pathway which will produce lactic acid using lactate dehydrogenase (LDH). Lactic acid buildup in the muscle would cause fatigue and pain.
Pyruvate Dehydrogenase Complex Deficiency (PDCD) is a rare genetic disorder. PDCD is caused by mutation on x-linked gene. There are some genes responsible for this deficiency because each enzyme in the PDC has their own gene but the common mutation, about 80% of cases, is on PDHA 1, gene responsible for making subunit alpha E1 enzyme. Another genes are PDHB (gene for subunit beta E1 enzyme), DLAT (gene for E2 enzyme), DLT (gene for E3 enzyme), PDHX (gene for E3 binding protein), PDP1 (gene for phosphatase). A patient with PDCD could not process glucose aerobically because the body does not has proper PDC which is necessary to make glucose enter aerobic pathway which results in anaerobic metabolism pathway of glucose and produces lactic acid.
When the amount of lactic acid in the blood is too high it would cause something called lactic acidosis. Some symptoms associated with lactate acidosis are:
1. vomiting
2. hyperventilation
3. nausea
4. abnormal heartbeat, etc
High level of lactic acid in the blood could also be dangerous because it could cause damage to the peripheral nerve which makes the patient unable to control and use their extremities well and could cause atrophy (decrease in muscle mass). Patient with PDCD could also has other neurological problem like seizure, intellectual disability, etc, and also could result in death. Most of the patient diagnosed with PDCD since their childhood could not survive until adulthood although some could survive.
Cure for this mutation still has not been found but there are some treatments which could be used to treat the patient. One of them is by going through a diet called ketogenic diet. The diet consist of high fat, adequate protein, and low carbohydrate. With this diet, it helps the body not to use glucose as the main source of energy because this could result in increase level of lactic acid in blood, but instead, makes the body to use dietary fat and protein as the source of energy by different metabolism pathway called beta oxidation and gluconeogenesis (I will discuss about these pathway on different post).
When the amount of lactic acid in the blood is too high it would cause something called lactic acidosis. Some symptoms associated with lactate acidosis are:
1. vomiting
2. hyperventilation
3. nausea
4. abnormal heartbeat, etc
High level of lactic acid in the blood could also be dangerous because it could cause damage to the peripheral nerve which makes the patient unable to control and use their extremities well and could cause atrophy (decrease in muscle mass). Patient with PDCD could also has other neurological problem like seizure, intellectual disability, etc, and also could result in death. Most of the patient diagnosed with PDCD since their childhood could not survive until adulthood although some could survive.
Cure for this mutation still has not been found but there are some treatments which could be used to treat the patient. One of them is by going through a diet called ketogenic diet. The diet consist of high fat, adequate protein, and low carbohydrate. With this diet, it helps the body not to use glucose as the main source of energy because this could result in increase level of lactic acid in blood, but instead, makes the body to use dietary fat and protein as the source of energy by different metabolism pathway called beta oxidation and gluconeogenesis (I will discuss about these pathway on different post).
