Kreb's Cycle Flashcards
Key CENTRAL metabolic pathway that connects carbohydrate, fat and protein metabolism
TCA cycle
Kreb’s cycle is used to generate
NADH
FADH
Molecules that can go in ETC and generate energy
Krebs cycle release stored energy or fats, carbs and proteins through
Oxidation
Originates even before life started
Origin of life from nonliving things
Abiogenesis
2 C acetate that enters the Krebs release these 2 molecules through
CO2
oxidation
In eukaryotic cells, citric acid cycle occurs in the
matrix of mitochondria
In prokaryotic cells, the citric acid is performed in the
Cytosol
Acetyl CoA comes from
Breakdown of 6C glucose to 3C compound pyruvate with transfer of 2 C from pyruvate to acetyl coA
additional carbon lost and 1 molecule of NADH produced
Converts pyruvate dehydrogenase to acetyl coA
Pyruvate dehydrogenase
Pyruvate dehydrogenase that converts pyruvate to acetyl coa needs the coenzyme to function effectively
Vitamin B5 Pantothenic Acid
Coenzyme A
Deficiency of pyruvate dehydrogenase
Decreased levels of Cytochromes a and aa3
Spasticity
Myoclonia
Demenita with hepatic cirrhosis
Alpers disease
Progressive Sclerosing Poliodystrophy
First step in TCA
by the enzyme
2 C acetyl CoA + 4 C oxaloacetate -> 6 C citrate
citrate synthase
Second step:
Citrate is converted into
by the enzyme
Isocitrate
Aconitase
Inhibitor of aconitase
Causes citrate accumulation -> block citric acid cycle
Fluorocitrate
Contained in rat poisons, flouroacetate is converted to this chemical by citrate synthase
Fluorocitrate
Step 3: Isocitrate is converted into
by the enzyme
with production of
Alpha ketoglutarate
Isocitrate dehydrogenase
NADH
*removes hydrogen aka oxidation
NAD -> NADH
H must be passed on to another molecule hence reduced
First oxidation reduction reaction of Krebs
6C Iso-citrate -> 5C Alpha ketoglutarate by isocitrate dehydrogenase
NAD -> NADH
Carbon atom removed from isocitrate in the form of CO2
“oxidative decarboxylation”
Step4: Alpha ketoglutarate becomes
by the enzyme
and yields
3 C Succinyl CoA
Alpha ketoglutarate dehydrogenase
NADH
Again, “oxidative decarboxylation”
Uses coenzyme A
NAD - NADH + CO2
Step 5: Succinyl CoA becomes
by the enzyme
4 C Succinate
Succinyl CoA SYNTHETASE
GDP -> GTP
Coenzyme A gets released, succinyl CoA loses its high free energy
The substrate level phosphorylation reaction in TCA
Succinyl CoA -> Succinate by Succinyl Coa synthetase
GDP -> GTP
Step 6: Succinate becomes
by the enzyme
produces
Fumarate
Removes H from succinate and accepted by FAD becoming FADH
FAD used because it requires lesser energy since 4C compound na lang sila
This enzyme uses Fe-S complex as in ETC
Succinate dehydrogenase
Complex II
Step 7: Fumarate becomes
by the enzyme
Malate
Fumarase
Water is added to fumarate
Step 8: Malate becomes
by the enzyme
Oxaloacetate
Malate dehydrogenase
“Oxidation”
NAD -> NADH for ETC
Because oxaloacetate is rapidly utilized for ETC and to generate citrate
Standard free energy for this cycle is significantly POSITIVE
+G of the TCA
Malate -> Oxaloacetate by malate dehydrogenase
NAD -> NADH
3 molecules of NADH generated from the TCA come from these enzymes
Isocitrate dehydrogenase
Alpha ketoglutarate dehydrogenase
Malate dehydrogenase
1 molecule of FADH is generated from this enzyme
Succinate dehydrogenase
Acetyl CoA + 3 NAD + FAD + GDP + P04 + 2H20 ->
2 CO2 + 3 NADH + FADH2 + GTP + CoA
1 molecule of GTP is formed by the enzyme
Succinyl CoA synthase
Also releases CoA
Succinyl CoA -> Succinate
2 molecules of water is formed by the enzyme
Citrate synthase (oxaloacetate + acetyl coa) Fumarase (fumarate -> malate)
How many ATPs in TCA
3 NADH (2.5 x 3) 1 FADH (1.5 x 1) 1 GTP ———————— 10 ATPs = 1 acetyl CoA in one turn
10 x 2 acetyl CoAs entered = 20 ATPs
High energy compound regenerated in TCA
Oxaloacetate
Synthesis and degradation
Pathway for oxidation of 2-C units
Provides substrates for AA synthesis by transamination
Provides substrates for gluconeogenesis and FA synthesis
Amphibolic pathway
TCA
Citrate synthase is inhibited by
ATP
Key cytoplasmic enzyme that facilitates the net transfer out of the Kreb’s cycle into the main pathway or GLUCONEOGENESIS
Phosphoenolpyruvate carboxykinase
PEPCK
Catalyzes the decarboxylation of oxaloacetate to phosphoenolpyruvate
Phosphoenolpyruvate carboxykinase
PEPCK
Phosphoenolpyruvate carboxykinase is induced by
Glucagon
Cortisol
End product (with energy) of TCA
3 NADH
1 FADH2
Rate limiting step of Krebs
Isocitrate -> alpha ketoglutarate by enzyme isocitrate dehydrogenase
TCA is stimulated by inc
ADP
TCA is inhibited by inc
ATP
NADH
FADH2
Amino acids that can enter TCA
Alanine (Pyruvate, Acetyl Coa)
Aspartate (Oxaloacetate)
Glutamate (a-ketoglutarate)
Discovered by Hans Krebs
Central pathway for recovering energy
Final common pathway for metabolism of CHO, lipids, proteins
1 cycle: 2 molecules CO2, 3 NADH, 1 FAD and 1 high energy compound (oxaloacetate)
Kreb’s cycle
