TCA or KREB’s CYCLE

- TCA happens in mitochondria

- TCA means TRICARBOXYLIC ACID CYCLE part of glucose and carbohydrate
metabolism

- TCA is the final pathway of oxidative catabolism of the fatty acids, proteins, and
carbohydrates
- Function of TCA: oxidation of acetyl CoA + (2) carbon dioxide, formation of ATP, GTP,
and Synthetic reactions (can be a source of glucose/gluconeogenesis)
- TCA it has close proximity to the electron transport system that is why it very important in
the production of ATP that snake it easier to reduce NADH and FADH
- TCA happens only in aerobic conditions
- Anaplerotique is the pilling up of the intermediates as a result of the TCA

ACETYL COA
- Acetyl CoA came from the oxidative decarboxylation of pyruvate with the enzyme named
pyruvate dehydrogenase complex but it is not part of TCA cycle because the
formation of Acetyl CoA happens outside the kreb’s cycle
- Pyruvate is the end product of the in aerobic glycolysis which will place in the cytosol
after but it must enter in mitochondrial membrane
- Pyruvate dehydrogenase complex is the enzyme used for the conversion of pyruvate to
acetyl CoA and it is composed of protein aggregate of multiple of three enzymes: e1 or
pyruvate decarboxylase, e2 or dihydrolipoyl transacetylase, & e3 or dihydrolipoyl
dehydrogenase
 - The composition of the PDHC has two regulatory enzymes: pyruvate dehydrogenase
kinase and pyruvate dehydrogenase phosphatase
- Coenzymes that are needed in PDHC enzymes:
- e1 needs thiamine pyrophosphate
- e2 needs lipoic acid & coenzyme A (CoA)
- e3 needs FAD and NAD
- Coenzymes can act as the carrier or oxidants of the intermediates
- pyruvate dehydrogenase kinase is responsible for the inactivation or inhibition of the
PDHC
- pyruvate dehydrogenase phosphatase responsible for the activation of the PDHC
- Where kinase is activated with the presence of the high ATP, NADPH and Acetyl CoA
- Phosphatase is activated when the there is low ATP and high ADP
- Increased in pyruvate dehydrogenase kinase there will be stable PDHC
- Increased in pyruvate dehydrogenase phosphatase, the PDHC works or reacts
- Pyruvate is the potent inhibitor of PDH kinase
- Calcium is a strong activator of PDh phosphatase
CITRATE
- Is the result of condensation of oxaloacetate and acetyl CoA from the enzyme of citrate
synthase
- If the citrate inhibit the citrate synthase, it will activates the acetyl CoA carboxylase and
PKF1
ISOCITRATE
- Is the result when the citrate was isomerase
- It is catalyzed by the Aconitase where there is a hydroxyl group migration
ALPHA KETOGLUTARATE
- Is the result of oxidative decarboxylation of isocitrate which the enzyme used is isocitrate
dehydrogenase
- Taking away or releasing of CO2 (dehydrogenase)
- Produce NADH
- (synthetic reaction) Is also from amino acid
SUCCINYL CoA
- Second release of CO2
- Is the result of decarboxylation of alpha ketoglutarate in the enzyme of Alpha
Ketoglutarate dehydrogenase
- Second production of NADH
- Is also from amino acid
SUCCINATE
- After the formation of the succinyl CoA cleavage that is catalyzed by the enzyme called
succinate thiokinase which it cleaves off the high-energy thioester band of succinyl CoA
- There is a phosphorylation of GDP to GTP
FUMARATE
- Is the result of Succinate oxidation that is catalyzed by the enzyme called succinate
dehydrogenase (only enzyme imbedded in the mitochondrial membrane)
- FAD becomes FADH
MALATE
- Is the result of fumarate hydration in the enzyme called Fumarase
- Is also from the amino acid
OXALOACETATE (OAA)
- Is formed by the enzyme malate dehydrogenase
- Final production of NADH
- Is also from amino acid

Result of Krebs cycle:

3NADH to 3NAD = 9
2 FADH to FAD = 2
1 GTP to ATP = 1
= 12 ATPs or acetyl CoA oxidize

REGULATION OF TCA
- 2 reactions: direct reaction and Indirect reaction
- Indirect reaction has two types: high energy state and low energy state
- High energy = high ATP, low ADP will lead to decrease oxidative phosphorylation and
this will lead to decrease oxidation of NADH leads to increase NADH/NAD ratio leads to
no need of TCA
- Low energy = opposite of high energy