TCA Flashcards
Aerobic pathways/ respiration
TCA
ETC / Oxidative Phosphorylation
Reactions that take place in TCA
decarboxylation
redox
hydrogenation/dehydrogenation
isomerization
TCA coenzymes
NAD and FAD
vitamin derivative of NAD
niacin or nicotinamide
vitamin derivative of FAD
riboflavin
vitamin derivative of CoA
pantothenic acid
Vitamin B derivatives of NAD, FAD, and CoA are
fat soluble
starting material for citric acid cycle
Acetyl CoA
converts pyruvate to Acetyl-CoA
pyruvate dehydrogenase complex
1 turn of TCA yields:
1 ATP
3 NADH
1 FADH2
Step 1
Acetyle CoA + Oxaloacetate ——> Citrate
Citrate synthase
reactions occuring in step 1
condensation
dehydration synthesis
number of carbons in oxaloacetate and Acetyle CoA
4C - Oxaloacetate
2C - Acetyl CoA
6C molecule product of step 1
Citrate
by product of step 1
CoA-SH
Step 2
Citrate —–> cis - Aconitate ——> Isocitrate
(reversible)
aconitase
tertiary alcohol which is not oxidizable
Citrate
secondary alcohol that can be oxidized
Isocitrate
Reactions in Step 2
Isomerization
dehydration
hydration
Step 3
Isocitrate ——–> Oxalosuccinase ———> a-ketoglutarate
isocitrate dehydrogenase
Reactions occuring in Step 3
Redox
decarboxylation
byproducts of Step 3
NADH
CO2
oxidizing agent in step 3
NAD+
ketone
formed when isocitrate is oxidized leading to reduction of NAD+ and decarboxylated
a-ketoglutarate
Step 4
a-ketoglutarate ———-> succinyl-CoA + CO2
a-ketoglutarate dehydrogenase complex
byproduct of Step 4
NADH
coenzyme added in step 4
CoA
Reactions in Step 4
Oxidation
bond formed by CoA
thioester bond
ketone
succinyl-CoA
Step 5
succinyl-CoA ———> succinate
(reversible)
succinyl-CoA synthetase
byproducts of Step 5
CoA-SH
GTP
Reactions in Step 5
thioester bond cleavage in succinyl-CoA
phosphorylation of GDP
Step 6
succinate ———> Fumarate (reversible)
succinate dehydrogenase
Reactions in step 6
Oxidation
-2H atoms
byproduct of step 6
FADH2
alkane
succinate
alkene
trans double bond
Fumarate
Step 7
Fumarate ———> Carbanion transition state ——> L-malate
fumarase
added to reaction in step 7
OH-
H+
cis double bond; toxic
L-malate
Step 8
L-Malate ———> Oxaloacetate
L-malate dehydrogenase
byproduct of Step 8
NADH
H+
oxidizing agent of Step 8
NAD
Regulation of TCA
Citrate
Citrate synthase
Isocitrate dehydrogenase
regulatory effector of the pathway
citrate
inhibited by ATP, NADH, succinyl CoA
citrate synthase
key regulatory enzyme
Isocitrate dehydrogenase
inhibits citrate synthase
ATP
NADH
succinyl-CoA
inhibits isocitrate dehydrogenase
ATP
NADH
stimulates isocitrate dehydrogenase
Ca2+
ADP
AMP
Fates of Acetyl CoA
TCA
Ketone bodies
Steroids or fatty acids
Redox reactions
3
4
6
8
Decarboxylation reactions
3,4
Dehydration reaction
2
Hydration reactions
2,7
Steps that produce NADH
3,8,4
Step the produces GTP
5
Step that produces FADH
6
Steps that release CoA-SH
1,5
Step that uses CoA-SH
4
Sources of pyruvate
Glucose (via glycolysis)
Lactic Acid (via oxidation)
Alanine (via deamination)
Glucogenic AA (via catabolism)
Fate of pyruvate
gluconeogenesis
conversion to lactate (via reduction)
conversion to OAA (via carboxylation)
conversion to ACoA (via oxidative decarboxylation)
synthesis of alanine (via transamination)
central step for linking glycolysis with TCA
Oxidation of pyruvate to Acetyl CoA
3C unit reaction: compartment: site: nature: enzyme: ATP produced:
pyruvate oxidative decarboxylation mitochondria all cells and tissues catabolic PDH 3 ATP per pyruvate
a cluster of 3 enzymes that requires 5 cofactors
PDH
Enzyme 1
Pyruvate dehydrogenase
Enzyme 2
Dihydro Lipoyl Trans Acetylase
Enzyme 3
Dihydro Lipoyl Dehydrogenase
Coenzymes in PDH complex
TPP - thiamine pyrophosphate CoA FAD NAD Lipoamide
aka thioctic acid
has 2 S atoms and C atoms
can accept or donate H atoms
lipoate/lipoic acid
decarboxylates pyruvate to make the enolic form of AcCoA
E1/ pyruvate dehydrogenase
cofactors in E1
TPP
Vit B1
turns this into regular AcCoA
E2
cofactors of E2
CoA
Lipoic acid
reconstructs lipoic acid
E2
FAD
Vit B2
Oxidizes FADH back to FAD
E3
NAD
Vit B3
nature of Acetyl CoA
amphibolic
rate limiting enzymes of TCA
Citrate synthase
Isocitrate DH
a-KG DH
total number of ATPs formed
38
Common metabolic pathway
3,4
Fuel for TCA
AcCoA
Oxidizing agent for formation of C-O double bond
NAD
Oxidizing agent for C-C double bond
FAD
Two C enter as-
Acetyl group of AcCoA
Two C leave as
CO2
4 Vitamins needed in TCA
Riboflavin
Nicotinamide
Pantothenic A
Thiamine
Catalyst of TCA
Regenerated
Can condense with many AcCoA
OAA
ATP produced in glycolysis
8
ATP produced in Oxidative decarboxylation of pyruvic acid
6
ATP produced in krebs
24
Methyl carbon of acetyl group is joined to carbonyl group (C2) of OAA
1
Hydroxyl group of citrate is exchanged for an H atom on an adjacent carbon
2
Isocitrate is oxidized by hydride transfer to NAD
Decarboxylation is facilitated by electron withrawal by bound Mn2+
3
H atom must be removed from SH Group for CoA to form high energy thioester bond
Identical to PDH reaction
4
Succinyl CoA’s thioester bond is hydrolyzed forming succinate which generates GTP
5
Succinate formed from succinyl CoA is oxidized by FAD to fumarate
6
Fumarate is hydrated to form L-malate
7
Oxidation of L-malate to oxaloacetate
8