Biochemistry lecture 22

Citric acid cycle

why must metabolic pathways be controlled?

To link supply with demand (storage and release)​

2) To allow cells/organisms to respond to environmental changes, eg. temperature, diet, microenvironment​

3) To maintain a constant internal environment (homeostasis)​

4) To enable different tissues to interact (eg. liver, adipose,muscle)​

Control of glycolysis mechanisms

Controlling the amount of an enzyme is very slow so often changing the activity is more important for control - achieved by allosteric control (still takes a bit more time) or phosphrylation (instantaneous, by kinases and dep by phosphatases

Control of glycolysis in process

Important enzymes:

Hexokinase - activated and deactivated by negative feedback

Phosphofructokinase - AMP activates this enzyme, fructose 2,6 bisphosphate (only in liver but biggest positive modulator of F6P to F16BP. 

Pyruvate kinase

F16BP accumulation activates action of pyruvate kinase 

Inhibition:

High ATP levels inhibit PFK and pyruvate kinase 

Also low pH 

Citrate accumulation inhibits PFK

Fates of pyruvate 

P enters into mitochondria

Once in, major pathway (oxidative decarboxylation) of pyruvate to acetyl coA losing a molecule of CO2 by enzyme pyruvate dehydrogenase 

Pyruvate dehydrogenase

(132 subunit multienzyme complex)​

(E1) Pyruvate dehydrogenase​

(E2) Dihydrolipoyl transacetylase​

(E3) Dihydrolipoyl dehydrogenase

Vitamins required for pyruvate entry into citric acid cycle

• B1 as thiamine pyrophosphate​

• Riboflavin as FADH2​

• Niacin as NAD

vitamin B1 deficiency

• Thiamine is found in grain husks and meat​

• Polished rice = deficiency​

• Beri-beri “extreme weakness”:​

• loss of appetite​

• lassitude​

• numbness of limbs and extremities​

• atropy

• Wernicke-Korsakoff encephalopathy​ - links to this issue in brain ​

Pyruvate conversion

To fatty acids and amino acids and lactate

When ATP levels are high acetyl CoA diverted to a more efficient storage molecule

During anabolic growth pyruvate isaminated to non-essential amino acids​

Under anaerobic conditions regenerate NAD+​ - lactate ​

​

Pyruvate to lactate 

Chemical drawings of pyruvate to lactate

Lactate dehydrogenase?

Pyruvate converted to ethanol​

Under anaerobic conditions regenerate NAD+​

Yeast and some bacteria​

Two step process to regenerate NAD+​

Citric acid cycle​

• Krebs cycle​

• TCA cycle

Purpose is to harvest high-energy electrons from carbon fuels​

What molecules are generated in CAC?

CAC stages 

What is generated at each stage of CAC?

Mnemonic for CAC

CAC

Is both catabolic and anabolic

Control of the CAC

Catabolism so far