Bioenergetics Flashcards
Aconitase defect
(TCA cycle deficiency)
Consequences: mitochondrial iron-sulfur protein deficiency in Friedreich ataxia
alpha-ketoglutarate dehydrogenase defect
(TCA cycle deficiency)
Consequences: Severe encephalopathy, hypotonia, psychotic behavior, pyramidal symptoms
Succinate dehydrogenase defect
(TCA cycle deficiency)
consequences: Leigh-like syndrome, paraganglioma, and pheochromocytoma, early-onset encephalomyopathies
Succinyl CoA synthase defect
(TCA cycle deficiency)
Consequences: encephalomyopathy and mtDNA depletion
Fumarase defect
(TCA cycle deficiency)
early encephalomyopathy, seizures, dystonia, uterine leiomyomas, papillary renal cell cancer
AA that replenish Oxaloacetate
Asparagine –> aspartate
AA that replenish Fumarate
phenylalanine, tyrosine, aspartate
AA that replenish Succinyl CoA
Threonine, Methionine, Isoleucine, Valine –> Propionyl CoA
AA that replenish a-ketoglutarate
Glutamine, Proline, Histidine, Arginine –> Glutamate
Complex 1 (NADH dehydrogenase)
- transmembrane protein, e- transfers facilitated by tightly bound FMN and Fe-S clusters
- Accepts 2e- from NADH and donates them to coenzyme Q
- pumps 4 H+ ions from matrix into intermembrane space
Complex II (succinate dehydrogenase)
(also TCA cycle enzyme)
- protein bound to matrix side of inner mitochondrial membrane, e- transfers facilitated by tightly bound FAD and Fe-S clusters
- transfers 2e- from FADH2 to coenzyme Q
Coenzyme Q (ubiquinone)
structure: lipophilic molecule, aromatic 6-member ring and long hydrophobic side chain. Mobile, moves freely within lipid bilater of inner mt.mem. converted to ubiquinol upon acceptance of 2e-.
* accepts 2e- from either complex 1 or complex 2, transfers them to complex 3
Complex 3 (cytochrome-c reductase)
structure: transmembrane protein, e- transfers facilitated by Fe-S clusters and cytocheomes -b and -c1, which harbor iron containing heme-b and -c molecules.
* accepts 22e- from ubiquinol and donates them to cytochrome-c
* pumps 2H+ from matrix into the intermembrane space
Cytochrome C
structure: small protein bound to intermembrane space side of inner mt.mem. Mobile, held to membrane via electrostatic forces. e- transfers are facilitated by an iron-containing heme c group.
* Accepts e- from complex 3 and donates them to Complex 4
Complex 4 (cytochrome-c oxidase)
structure; transmembrane protein, e- transfers facilitated by Cu centers and cytochromes -a and -a3, harbor iron containing heme-a molecules.
- accepts electrons from cytochrome-c and transfers them to O2 (forming water)
- pumps 4H+ from matrix to intermem.space
Complex 5 (ATP synthase)
structure: multisubunit transmembrane protein, proton movement facilitated by its membrane spanning Fo domain, and ATP synthesis is facilitated by its F1 domain, which protrudes into the matrix
* moves protons from the intermem.space into matrix to obtain energy needed to synthesize ATP from ADP and Pi
Pyruvate dehydrogenase complex (PDC)
3 enzymes (E1, E2, E3) and 5 coenzymes (TPP, CoA, Lipolic Acid, FAD, NAD+)
catalyzes decarboxylation of pyruvate:
pyruvate –> CO2 + Acetyl CoA + NADH
phospho form is inactive, dephos form is active
-pyruvate dehydrogenase phosphatase activates (+ by Ca2+ and Mg2+)
- pyruvate dehydrogenase kinase inactivates (+ by Acetyl CoA, NADH, ATP, - by pyruvate, CoA, NAD+ ADP)
PDC deficiency
PDC is always inactive - neonatal lactic acidosis
glucose converted to lactate instead of acetyl CoA (PDC cannot decarbox pyruvate –> acetyl CoA)
causes lactic acidosis (affecting CNS), ketogenic diet recommended
- gene for E1 is on X chromosome
Arsenite and lipolic acid
lipolic acid subunit modified by arsenite - arsenite links to lipolic acid suflydryl groups irreversibly and limits the available lipolid acid
many enzymes use LA as a coenzyme, these are all limited. slow poison
each turn of TCA produces
1 OAA, 2 CO2, 3NADH, 1 FADH2, 1 GTP
TCA irreversible rxns by
citrate synthase, isocitrate dehydrogenase, alpha ketoglutarate dehydrogenase
TCA step 1 &2
Condensentation and isomerization
Acetyl acid + OAA (enz citrate synthase) –> Citrate –> (enz aconitase) isocitrate
*Citrate synthase catalyzes irreversible rxn
TCA step 3&4
oxidations and decarboxylations –> NADH, CO2, Succinyl CoA
**Rate limiting step is catalyzed by isocitrate dehycrogenase
isocitrate –(oxidized &decarbox by isocitrate dehydrogenase)–> alpha ketoglutarate –> succinyl CoA
*a-ketoglut dehyrd. requires same 5 coenzymes as PDC
TCA step 5
cleavage of succinyl coA to generate succinate and GTP
- catalyzed by succinyl thiokinase (succinyl coA synthetase)
