Does pyruvate dehydrogenase require thiamine?

Vitamin B1 (thiamine) is a co-factor for pyruvate dehydrogenase, an essential enzyme for aerobic metabolism. In the absence of thiamine, the conversion of pyruvate to acetyl-CoA is inhibited and pyruvate cannot enter the Kreb’s cycle.

What happens when pyruvate dehydrogenase deficiency?

The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well.

What is the role of thiamine pyrophosphate in the pyruvate dehydrogenase complex?

TPP is a cofactor in decarboxylation reactions of alpha-keto acids including pyruvate decarboxylation by pyruvate dehydrogenase complex, which connects the Embden-Meyerhof pathway to oxidative phosphorylation by feeding acetyl-CoA into the Krebs cycle.

What is pyruvate dehydrogenase deficiency?

Pyruvate dehydrogenase complex deficiency (PDCD) is a rare disorder of carbohydrate metabolism caused by a deficiency of one of the three enzymes in the pyruvate dehydrogenase complex (PDC). The age of onset and severity of disease symptoms vary widely.

How does vitamin B1 help the body?

Function. Thiamin (vitamin B1) helps the body’s cells change carbohydrates into energy. The main role of carbohydrates is to provide energy for the body, especially the brain and nervous system. Thiamin also plays a role in muscle contraction and conduction of nerve signals.

How long do thiamine stores last?

Thiamine is a water-soluble vitamin stored primarily in the liver; however, storage only lasts up to 18 days. The absorption of thiamine occurs in the duodenum by an active process and is converted to its active form thiamine pyrophosphate.

Is pyruvate dehydrogenase deficiency fatal?

Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders.

What causes low pyruvate?

PC deficiency is caused by changes (mutations) in the pyruvate carboxylase (PC) gene resulting in a missing or decreased amount of pyruvate carboxylase enzyme. This enzyme functions in the energy producing centers of cells (mitochondria) to make oxaloacetate.

How does thiamine deficiency cause neurological problems?

Thiamine deficiency causes a disorder of energy metabolism in brain cells that leads to mobility impairments of neurotransmitters, thus resulting in neurological symptoms like those seen in Wernicke encephalopathy.

What are the symptoms of pyruvate carboxylase deficiency?

PC deficiency type A (infantile form) begins in infancy and symptoms include developmental delay, intellectual disability, mixed acid-base disturbance with mild to moderate elevations in lactic acid and ketone bodies in the blood (lactic acidosis/ketoacidosis), abdominal pain, vomiting, tiredness and muscle weakness.

How is pyruvate dehydrogenase deficiency diagnosed?

PDC deficiency is diagnosed based on laboratory tests including blood tests, analysis of the urine, and brain MRI. The diagnosis can be confirmed by analyzing the pyruvate dehydrogenase enzyme . Treatment for PDC deficiency includes dietary supplementation with carnitine, thiamine, and lipoic acid.

How to treat pyruvate dehydrogenase complex deficiency ( PDC )?

The diagnosis can be confirmed by analyzing the pyruvate dehydrogenase enzyme. [1] [2] Treatment for PDC deficiency includes dietary supplementation with carnitine, thiamine, and lipoic acid. [1]

Why are the symptoms of PDC deficiency variable?

The brain is a part of the body that requires a lot of energy, so the symptoms that are first seen when energy is lacking often affect the brain. The signs and symptoms of PDC deficiency are variable because the amount of enzyme that is available to create energy varies in different people with the disease. [1]

What happens when pyruvate is not converted into acetyl-CoA?

The pyruvate instead is turned into lactic acid, which is toxic to the body in large amounts and causes lactic acidosis. When pyruvate isn’t converted into acetyl-CoA, the body also can’t go through the citric acid cycle.

When does PDC deficiency cause lactic acidosis?

[1] [4] There is a wide range of severity of symptoms associated with PDC deficiency. In some cases, the disease is less severe, and episodes of lactic acidosis only occur when a person is ill, under stress, or eats a high amount of carbohydrates.