Transition Stage of Cellular Respiration Quiz

Transition Stage of Cellular Respiration

• Pyruvate, a 3-carbon molecule, is the end product of glycolysis.
• Two pyruvate molecules are generated from one glucose molecule.
• Pyruvate enters the mitochondria and is converted to acetyl-CoA in the presence of oxygen.
• NADH from glycolysis carries electrons to the electron transport chain in the presence of oxygen.
• In the absence of oxygen, NADH reduces pyruvate to lactic acid.

Pyruvate Dehydrogenase Complex

• Pyruvate dehydrogenase complex (PDH complex) consists of 3 enzymes:
  • Enzyme 1 (Pyruvate dehydrogenase): contains thiamine pyrophosphate (TPP) as a cofactor.
  • Enzyme 2 (Dihydrolipoamide acetyltransferase): contains lipoic acid with disulfide bonds.
  • Enzyme 3 (Dihydrolipoamide dehydrogenase): contains FAD and NAD+.

Regulation of the Pyruvate Dehydrogenase Complex

• PDH complex activity is tightly regulated via phosphorylation and dephosphorylation.
• Pyruvate dehydrogenase kinase (PDK) phosphorylates enzyme 1, inhibiting PDH complex activity.
• Pyruvate dehydrogenase phosphatase (PDP) dephosphorylates enzyme 1, activating the PDH complex.

Factors that Regulate PDH Complex Activity

• High energy levels: ATP, acetyl-CoA, NADH stimulate PDK, inhibiting the PDH complex.
• Low energy levels: ADP, pyruvate, calcium inhibit PDK, activating the PDH complex.
• Hormonal Regulation: Insulin activates PDP, promoting dephosphorylation and activation of the PDH complex.

Clinical Relevance

• Thiamine Deficiency: A deficiency in thiamine causes Beriberi, a neurological disorder characterized by pain, paralysis, and edema.
• Alcoholism: Alcohol consumption contributes to thiamine deficiency due to its lack of nutritional value, causing beriberi.
• White Rice Diet: A diet solely based on white rice lacks sufficient thiamine, also causing beriberi.
• Wernicke-Korsakoff syndrome: A disorder associated with thiamine deficiency and alcohol abuse, characterized by neurological abnormalities including memory impairment, confusion, and eye movement disorders. Confabulation is a feature of Wernicke-Korsakoff syndrome.

Steps in Pyruvate Dehydrogenase Complex Reaction

• Step 1: Pyruvate reacts with TPP in enzyme 1, releasing CO2 and forming a two-carbon acetyl group bound to TPP.
• Step 2: The acetyl group is transferred from TPP to lipoic acid in enzyme 2, breaking the disulfide bond, forming acetyl-lipoate.
• Step 3: Coenzyme A reacts with the acetyl group on lipoate, forming acetyl-CoA.
• Step 4: The reduced lipoate releases hydrides, which are picked up by FAD, forming FADH2.
• Step 5: NAD+ accepts the hydrides from FADH2, generating NADH.

Summary of Pyruvate Dehydrogenase Complex Reaction

• Inputs: Pyruvate, TPP, lipoic acid, coenzyme A, FAD, NAD+
• Outputs: Acetyl-CoA, CO2, FADH2, NADH

Pyruvate Dehydrogenase Complex (PDC)

• Function: Converts pyruvate to acetyl-CoA, producing CO2 and NADH.
• Regulation:
  • Inhibition: High ATP, high NADH, high acetyl-CoA, and low ADP
  • Stimulation: Low ATP, high ADP, high pyruvate, calcium and insulin (activates PDP)
• Enzymes:
  • Pyruvate Dehydrogenase (E1): Uses TPP to remove CO2.
  • Dihydrolipoamide Acetyltransferase (E2): Contains lipoic acid, disulfides, and thiols.
  • Dihydrolipoamide Dehydrogenase (E3): Contains FAD and NAD.
• Deficiencies:
  • Thiamine Deficiency: Leads to Wernicke-Korsakoff Syndrome (psychological issues like confabulation) and Beriberi (neurological issues like pain, paralysis, and swelling).
  • Beriberi Causes: Genetic predisposition, alcohol abuse, high white rice consumption.

Confabulation

• Definition: Fabricating information to fill in memory gaps.
• Wernicke-Korsakoff Syndrome: Characterized by confabulation rather than memory recall.

Test your knowledge on the transition stage of cellular respiration, focusing on the conversion of pyruvate to acetyl-CoA and the role of the Pyruvate Dehydrogenase Complex. Explore the enzymes involved, their regulation, and the importance of oxygen in this crucial metabolic process.