Transition step and TCA cycle

Transition step

Conversion of pyruvate to acetyl-CoA occurs in the mitochondria linking glycolysis and the TCA cycle. Catalysed by the PDH. The cofactors are Mg2+, Thiamine pyrophosphate, FAD, Lipoic acid, CoASH, NAD+.

1. Carboxyl group gets removed forming CO2

2. NAD+ gets reduced to NADH

3. Coenzyme A gets attached to acetate, forming acetyl CoA

PDH

Pyruvate Dehydrogenase Complex. Regulated by phosphorylation (active) dephosphorylation (inactive).

1. Pyruvate dehydrogenase: inhibited by high ATP and GTP, activated by high AMP, Ca2+ and pyruvate

2. Dihidrolipoyl transacetylase: inhibited by high acetyl coa, activated by high CoA-SH

3. Dihydrolipoyl dehydrogenase: inhibited by high NADH, activated by high NAD+

Mitochondrial pyruvate carrier

Located in the inner mitochondrial membrane and aids in transporting pyruvate from the cytosol into mitochondrial matrix, where it can be further processed for energy production.

Acetyl CoA cannot directly cross the mitochondrial inner membrane into the matrix.

Arsenic poisoning

PDH has lipoamide sulphydryl group to which arsenic and organic arsenicals can bind and thus these compounds can inhibit PDH. The enzyme alpha ketoglutarate dehydrogenase can also be inhibited since it resembles PDH.

Important about TCA

1. The energy for the synthesis of citrate in reaction 1 comes from the hydrolysis of the thick ester.

2. In reaction 2, a symmetrical compound is converted into an asymmetrical compound.

3. GTP is equivalent to ATP since it can phosphorylate ADP to yield ATP and GDP in a reaction catalysed by nucleotide diphosphate kinase

4. By reaction 4, all six carbons from glucose have been converted to CO2

Products of TCA

4 CO2

6 NADH

2FADH2

2 GTP

Amphibolic because it involves catabolic (end with TCA cycle intermediates) and anabolic reactions (start from the cycle’s intermediates)

Regulation of TCA

1. Isocitrate dehydrogenase: inhibited by high NADH. Activated by high Ca2+ and ADP

2. Alpha ketoglutarate: inhibited by high NADH and succinyl CoA. Activated by high Ca2+