Respiratory Metabolism and Mitochondrial Disorders

Flashcards for reviewing respiratory metabolism, ATP synthesis, and related genetic disorders.

Krebs/Citric acid/TCA cycle

The main mechanism used to capture energy from carbohydrates, amino acids, or fats in cellular metabolism.

Glycolysis

Splits the 6 carbon glucose into two three carbon compounds, ultimately pyruvate.

Krebs Cycle Key points

3 x NADH, 1xFADH2 and 1xGTP are produced per Acetyl CoA. Occurs in the mitochondrial matrix.

Mitochondrial outer membrane

Has pores that make it permeable to small molecules and ions, but not to proteins.

Mitochondrial inner membrane

Convolutions (cristae) provide a very large surface area.

Chemiosmotic Model for ATP Synthesis

Electron transport sets up a proton-motive force, which drives the synthesis of ATP.

LHON

Leber hereditary optic neuropathy.

MERRF

Myoclonic Epilepsy & Ragged-Red Fibre Disease.

Kidney epithelial cell staining

Mitochondria - gold, Actin filaments - red, Nuclei - green

Mitochondrial segregation

Unequal separation of mitochondria during cell division produces heterogeneity amongst daughter cells.

Maternally inherited

Diseases associated with the mitochondrial genome are inherited from this parent.

ETC genetic origin

All ETC complexes, except Complex II, have a double genetic origin.

MELAS

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.

MERRF

Myoclonic epilepsy with ragged red fibres.

Kearns-Sayre syndrome (KSS)

Results from large heteroplasmic mtDNA deletions frequently detected in skeletal muscle.

Pearson syndrome

Results from large heteroplasmic mtDNA deletions in all tissues.

adPEO (Autosomal-dominant external ophthalmoplegia)

Multiple mtDNA deletions in muscle tissue, caused by autosomal mutations in mtDNA polymerases and Twinkle Helicase

Mitochondrial DNA depletion syndrome (MDS)

Neurological symptoms & liver failure.

PUS1 (pseudouridine synthase)

Myopathy and sideroblastic anaemia

Dichloroacetate (DCA)

Dichloroacetate lowers blood lactate in individuals with congenital lactic acidosis associated with mitochondrial dysfunction.

L-arginine

Vasodilation; reduces chance of stroke-like episodes.

Co-enzyme Q and Idebenone

Used to treat RC disorders where electron flux through the respiratory chain is inadequate; good anti-oxidants and can serve as protective scavengers for reactive oxygen species

Riboflavin

Vitamin B2; precursor for the prosthetic groups of complex I (NADH dehydrogenase) - FMN and complex II (succinate dehydrogenase) - FAD

Retroviruses

Integrate their DNA onto chromosome

Adenoviruses

Introduce their DNA into the nucleus but do not integrate into host DNA

Mitochondrial replacement therapy (MRT)

A new form of IVF where mutant mitochondrial DNA (mt-DNA) is replaced with donor DNA.