Acetyl CoA is generated in these 5 oxidation pathways
fatty acids, glucose, amino acids acetate and ketone bodies
THE substrate for the TCA cycle
Acetyl CoA
Oxidation of 2 carbon acetyl group energy is conserved as ____, _____, and ____.
NADH, FAD(2H) and GTP
TCA generates energy via ____ _____.
cellular respiration
Oxidative decarboxylation of alpha-ketoglutarate is catalyzed by this complex
alpha-ketoglutarate dehydrogenase complex
coenzymes of the alpha-ketoglutarate dehydrogenase
TPP, lipoate and FAD
alpha-ketogluturate dehydrogenase complex is anlagous to this complex of glycolysis
pyruvate dehydrogenase complex
This substrate is used and regenerated in each turn of the cycle
Oxaloacetate
When cells use intermediates of TCA or biosythetic rxns, the carbons must be replaced by anaplerotic rxns like this
pyruvate carboxylase reaction
anaplerotic definiton
filling-up
Where TCA cycle occurs
mitochondrion
Flux of RCA is coordinated with the rate of these 2 things
electron-transport chain and oxidative phosphorylation
This reflects demand for ATP in TCA cycle
feedback
Change the rate of ATP utilization
response of enzyme to ADP, NADH/NAD+ ratio, rate of FAD(2H) oxidation [Ca2+]
2 consequences of impaired TCA cycle
- inability to generate ATP from fuel oxidation 2. accumulation of TCA cycle precursors
most common cause of impaired function of the TCA cycle
lack of oxygen to accept electrons in electron-transport chain
this DNA is not bound to histones in a chromatin structure
mitochondrial DNA
within each cell there is multiple ______ and each of these also has multiple copies of this_____.
mitochondria, genome
mitochondria diseases
diminshed capactity to create energy, neuro problems (seizures, MR, epilepsy), progressive diseases
elevated ROS production found in these diseases
cancer and diabetes
2 carbons into TCA yieds
2 CO2
this enzyme links glycolysis to the TCA cycle
PDH
protein transport that transports pyruvate into the mitochondria
mitochondrial pyruvate carrier (MPC)
number of subunits in puruvate dehydrogenase
4
acitivator of PDH kinase
acetyl CoA NADH
inhibitor of PDH kinase
pyruvate ADP
activates PDH phosphatase
Ca 2+
oxaloacet + acetyl CoA –> citrate, enzyme?
citrate synthase (4C + 2C = 6C)
succinate dehydrogenase oxidizes succiate making this and reducing this substrate
double C bond, FAD
tumor supressor enzyme
SDH
net result of TCA
3 NADH + H+, 1 FAD(2H) + 1 GTP = 10 ATP
amine transfer cofactor
PLP
rxn in TCA that have positive delta g
malate –> oxaloacetate, citrate –>isocitrate
irreversible reactions of TCA cycle
those catalyzed by citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase
ratio of citrate to isocitrate
20:01
source of acetyl CoA
beta oxidation of fa, ketone bodies, acetate, glucose, alanine and serine, leucine and isoleucine
major anaplerotic enzymes in cell
pyruvate carboxylase
only enzyme embedded in the inner mitochondrial membrane
succinate dehydrogenase
extreme muscle pain during exertion, lack of ammonia build-up, mutation on the gene coding of muscle specific AMPD1 isoform of AMP deaminase
myoadenylate deaminase deficiency
TCA cylcle product that enters the electron transport chain
NADH
electron flow in the chain Hydrogen to this location
intermembrane space
complex order ETC w/NADH
I, III, IV
complex order Etc w/FAD
II, III, IV
Oxidation of one NADH pumps this many protons
4
major source of ROS
CoQ to molecular oxygen
complex I, # protons
nADH dehydrogenase, 4
complex III, # protons
cytochrome b-c1 complex, 4
complex Iv, # protons
cytochrome c oxidase, 2
product of etc
water
complex II, # protons
succinate dehyrogenase, 0
protons pumped NADH, FAD
10, 6
twelve protons complete one turn of rotos and generate ?
3 ATP
of alpha beta pairs in stalk of ATP synthase
3
excess energy from NADH –> H20
used to make use warm blooded
when electron transport stops
at rest, ATP to ADP is high, no final acceptor of electron (no oxygen)
this proton channel allows fat to be used for heat
UCP1 (thermogenin, uncoupling protein)
chemical uncoupler used to lose weight
DNP (dinitrophenol)
energy for transport across inner mitochondrial membrane comes from
electrochemical and pH gradient
3 basic type of transporters
antiporters, symporters, uniporters
mitochondrial permeability transition pore is brought on by this
hypoxia
block complex I
pesticide, barbituate
block complex III
antimycin A
block complex IV
cyanide, CO, Azide
Block complex V
Oligomycin
Block mitochondrial DNA replication
AZT
PDH subunits
e1-pyruvate decarboxylase(TPP)
E2-transacetylase (lipoate)
E3-dihydrolipoyl dehydrogenase (NAD+,FAD)
X-transacetylase(Co-ASH)
Anaplerotic reaction to make oxaloacetate.
Pyruvate via pyruvate carboxylase. Activated by acetyl coA
disease characterized by inability to control movements, seizures etc
leigh’s disease
cause of leigh’s disease
inherited mutation in the gene encoding E1alpha subunit of PDH