11TCA

TCA Biochemistry II

李卫芳

Email ：liwf@https://www.360docs.net/doc/718580130.html,

Phone: 3606284

TCA

Referred books:

Lehninger, Principles of Biochemistry (4 ed)

David L. Nelson, Michael M.Cox

https://www.360docs.net/doc/718580130.html,/pob4e_sample_content/生物化学（3ed），王镜岩

https://www.360docs.net/doc/718580130.html,/lehninger

TCA Chapter 11 Citric Acid Cycle Tricarboxylic acid cycle

(TCA cycle)

Krebs cycle

2007/03/20

TCA SIR HANS ADOLF KREBS

1953 Nobel Laureate in Medicine

for his discovery of the citric acid cycle

Background

1900-1981

Place of Birth: Hildesheim, Germany

Residence: Great Britain

Affiliation: Sheffield University

11.1 Production of Acetyl-CoA

11.2 Reactions of the Citric Acid Cycle 11.3 Regulation of the Citric Acid Cycle

11.4 The Glyoxylate Cycle

TCA TCA－－

Taken place－－

Eukaryotes: mitochondria

Prokaryotes: cytosol

TCA

cellular respiration --Rather than being reduced to lactate,ethanol, or some other fermentation product, the pyruvate produced by glycolysis is further oxidized to H2O and CO2.

TCA

1. Production of Acetyl-CoA-----Pyruvate Oxidation

A Major Entry Route for Carbon into the Citric Acid Cycle Pyruvate Dehydrogenase Complex

Pyruvate Dehydrogenase Complex

TCA three enzymes

1. Pyruvate Dehydrogenase(E1)

2. Dihydrolipoyl transacetylase(E2)二氢硫辛酰转乙酰基酶

3. Dihydrolipoyl dehydrogenase(E3)二氢硫辛酰脱氢酶

and five coenzymes

1. Thiamine Pyrophosphate焦磷酸硫胺素, 辅羧酶(TPP)

2. Lipoic Acid-lipoamide硫辛酰胺

3. FAD

4. NAD+

5. CoASH

The reactive carbon atom

TCA

TPP is the coenzyme form of vitamin B1

(thiamine)

In the reaction catalyzed by pyruvate decarboxylase, two of the three carbons of pyruvate are carried transiently on TPP in the form of a hydroxyethyl羟乙基or “active acetaldehyde乙醛”group which is subsequently released as acetaldehyde

羟乙基TPP

①The TPP carbanion负碳离子acts as a

nucleophile, attacking the carbonyl group of pyruvate.

②Decarboxylation produces a carbanion

that is stabilized by the thiazolium ring.

③Protonation to form hydroxyethyl TPP

④release of acetaldehyde.

⑤ A proton dissociates to regenerate the

carbanion.

TCA 3`5`-ADP

TCA

硫辛酸

TCA Cryoelectron 冷冻电子显微镜术micrograph of

PDH complexes isolated from bovine kidney.

Three dimensional image of PDH complex

The core (green) consists of 60 molecules of E2, arranged in 20 trimers

The lipoyl domain of E2 (blue) reaches outward to touch the active sites of E1 molecules (yellow)

A number of E3 subunits (red) are also bound to the core, where the swinging arm on E2 can reach their active sites.

TCA

1. E1 accepts a two carbon aldehyde from the decarboxylation of pyruvate.

2. The aldehyde group is transferred to the first lipoamide arm of E2.

3. The acetyl group is linked to CoASH, forming acetyl-CoA.

4. E3 oxidizes the reduced lipoamide arm by transferring two hydrogens to FAD, forming FADH

is oxidized by NAD+, forming FAD and NADH + H+.

5. FADH

TCA In Substrate Channeling

Intermediates Never Leave the Enzyme Surface

All these enzymes and coenzymes are clustered

allowing the intermediates to react quickly without diffusing away from the surface of the enzyme complex.

TCA 16.2 Reactions of citric acid cycle

central metabolic pathway中心代谢途径

1.generates NADH and FADH2for use in electron transport

2.produces GTP via substrate-level phosphorylation

3.Many metabolic processes use intermediates of the citric

acid cycle in their pathways.

TCA

TCA The Citric Acid Cycle Has Eight Steps Steps1,3,and 4 are

essentially irreversible in

the cell

Step5 may be either ATP or GTP

Four steps in this

process are oxidations,

energy of oxidation ----

NADH and FADH2.