Pyruvate

Dehydrogenase
Complex
Deficiency (PDCD)
Kylie Leeper
Andreina Martin
Matthew Melley

What is PDCD?
Pyruvate Dehydrogenase Complex Deficiency is
a disorder that affects the breakdown of
carbohydrates during energy metabolism in
the mitochondria.

PDC
Pyruvate + NAD+ + CoA ---> AcetylCoA +NADH + H+ + CO2

Pyruvate Dehydrogenase Complex

Contains 3 enzymes E1, E2, E3
E1: Pyruvate dehydrogenase
E2: Dihydrolipoyl transacetylase
E3: Dihydrolipoyl dehydrogenase
regenerate coenzymes and changes pyruvate
onto acetyl CoA

Pyruvate Dehydrogenase Complex

5 Key Coenzymes and Cofactors of PDC
Thiamine pyrophosphate (TPP)
Lipoate
Coenzyme A
FAD
NAD+

Pyruvate Dehydrogenase Complex

Cause of PDCD
Mutation in one of the 3 enzymes in the PDC
Commonly a mutation in the short arm of the
X-linked chromosome E1-alpha subunit
pyruvate dehydrogenase gene (PDHA1)

Inheritance Patterns
X-linked recessive mutation affecting PDHA1
gene (80%)
Females can be carriers
It can also occur spontaneously in the gene
(75%)

Signs & Symptoms:

Lactic acidosis
nausea
vomiting
severe/rapid breathing
problems
abnormal heartbeat

poor feeding habits

lethargy

Neurologic Problems:
intellectual disability
weak muscle tone (hypotonia)
seizures
poor coordination (ataxia)
abnormal eye movement
poor visual tracking
brain malformations
Other:
abnormal brain structures
atrophy of cerebral cortex

Diagnosis
Blood Test
Abnormal levels of PDC enzymes or function in
leukocytes or fibroblasts
High levels of lactic acid

Tissue biopsy

Prevalence
Most common neurodegenerative disorder
associated with abnormal mitochondrial
metabolism.
Males: severe disease and early death.
Females: progressive symptoms.
Mild/moderate because of variable Xchromosome activity.

Nutritional Implications
Restrictive diet
Energy obtained from
ketones, rather than
glucose.

Nutrition
Ketogenic diet: low carb, low protein, high fat.
fat fatty acids & ketone
bodies for energy
To reduce blood lactic acid
levels
helps with epilepsy
not always successful

Treatment & Therapy

Carnitine, Lipoic acid and Thiamine
Oral citrate and Sodium bicarbonate
Anti-seizure medications
*Neurological damage

Lipid Metabolism (Beta Oxidation)

Consists of 5 steps:
1. Activation- Formation of CoA thioester of a fatty acid.
2. Oxidation- Dehydrogenation at -and carbons formation of a
C=C bond.

3. Hydration-

Addition of water creates secondary alcohol on

carbon.

4. Oxidation- Oxidation of hydroxyl group to a ketone group.

5. Cleavage- Reaction with CoA to produce acetyl-CoA for use in
TCA Cycle.

Activity!
How many of each is produced or occurs during oxidation of a 16 carbon fatty acid? How much ATP is
yielded from each and total?
Acetyl-CoA=
Amount of -oxidations=
NADH=
FADH2=

Answer!
Acetyl-CoA = 8 Acetyl x 12 ATP =
Amount of -oxidations = 7
NADH = 7 x 3 ATP =
FADH2 = 7 x 2 ATP =

96 ATP

TOTAL

131 ATP - 2 ATP for activation

129 ATP

21 ATP
14 ATP

Activity!
5 volunteers please!

Case Study: Alex Salem

https://www.youtube.com/watch?v=UxQ_3z6
SK9M

References:
Brown, G.Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1016663/pdf/jmedgene00001-0059.pdf
Frye, R. (2014, April 11). Pyruvate Dehydrogenase Complex Deficiency: Background, Pathophysiology, Epidemiology. Retrieved from
http://emedicine.medscape.com/article/948360-overview
Mystery Diagnosis - Lethal Diet - Pyruvate Dehydrogenase Complex Deficiency (PDCD) - Part Two. (2012, January 7). Retrieved from
https://www.youtube.com/watch?v=UxQ_3z6SK9M
Patel, K. (2012). Retrieved from http://endocrinology.medicine.ufl.edu/files/2012/04/MGM-Stacpoole-Patel1.pdf
PDCD-The United Mitochondrial Disease Foundation. (n.d.). Retrieved from http://www.umdf.org/site/c.8qKOJ0MvF7LUG/b.8852461/k.B677/PDCD.htm
Pyruvate - Biology-Online Dictionary. (2008, July 29). Retrieved from http://www.biology-online.org/dictionary/Pyruvate
Pyruvate Dehydrogenase Complex Deficiency - NORD (National Organization for Rare Disorders). (n.d.). Retrieved from https://rarediseases.org/rarediseases/pyruvate-dehydrogenase-complex-deficiency/
Pyruvate dehydrogenase deficiency - Genetics Home Reference. (2012, July). Retrieved from http://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenasedeficiency