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BC21D: Bioenergetics & Metabolism. The formation of Acetyl Coenzyme A: Pyruvate dehydrogenase  -oxidation Amino acid catabolism. [email protected] The formation of Acetyl Coenzyme A. BC21D: Bioenergetics & Metabolism.

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Bc21d bioenergetics metabolism
BC21D: Bioenergetics & Metabolism

The formation of Acetyl Coenzyme A:

  • Pyruvate dehydrogenase

  • -oxidation

  • Amino acid catabolism

[email protected]


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Pyruvate and acetyl CoA are important metabolites at the intersection of many carbon-metabolising pathways.


Metabolic relationship between

carbohydrate and fat catabolism

Pyruvate

Carboxylase

Pyruvate

Dehydrogenase

Complex


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Let us look at pyruvate first.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Pyruvate is the normal 3-carbon product of carbohydrate catabolism


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

1. Glycolysis by either the EMP pathway, or variants such as PPP/HMP.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

1. Glycolysis by either the EMP pathway, or variants such as PPP/HMP.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

These fermentative pathways have PK as the last enzyme.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Recall that PK is an important regulatory enzyme in some cells.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Apart from being the normal product of carbohydrate fermentative catabolism, pyruvate is often produced by two other metabolic circumstances……..


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

2. Aerobic oxidation of lactate, e.g. by heart or liver isoenzymes of Lactate dh.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

2. Aerobic oxidation of lactate, e.g. by heart or liver isoenzymes of Lactate dh.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

3. Oxidative deamination of alanine, e.g. by liver after release from skeletal muscle during fasting.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

3. Oxidative deamination of alanine, e.g. by liver after release from skeletal muscle during fasting.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Lets us now look at pyruvate dehydrogenase


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

pdh reaction mechanism


BC21D: Bioenergetics & Metabolism

The formation of Acetyl Coenzyme A

pdh reaction mechanism



The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Pdh is regulated by

reversible, inhibitory phosphorylation of E1.


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Pdh is regulated by 4 reversible, inhibitory kinases of E1. The kinases have differing tissue specificities.

The kinases are activated

by increasing the ratios

of: [NADH]/[NAD];

[acetyl CoA]/[CoA];

[ATP]/[ADP]

The kinases are inhibited by pyruvate.

Insulin stimulates dephosphorylyation.


Regulation of the Pyruvate Dehydrogenase Complex

Pyruvate dehydrogenase phosphatase

“Pyruvate dehydrogenase kinase”, actually….

Pyruvate dehydrogenase complex

Pyruvate dehydrogenase kinases 1 – 4, with different tissue specificities

Phosphorylation sites on

Pdh subunit E1


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Apart from carbohydrates, carbons from other molecules can form acetyl CoA.

CHO


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Parts of

leucine

isoleucine

tryptophan

are degraded to acetyl CoA


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Lets us now look at fatty acid degradation


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism


Figure 3 Modulation of CPT I activity by carbohydrates

The pathway shown in red is the established pathway for the inhibition of hepatic CPT activity by carbohydrates. The other pathways shown are alternative routes that may be operative in heart

Abbreviations : CPT, carnitine palmitoyl transferase ; CAT, carnitine acetyl transferase.

The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism


The formation of Acetyl Coenzyme A

BC21D: Bioenergetics & Metabolism

Just to remind you where

we are going with this!


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