Lecture 02, 3

• What is the source of cytoplasmic pyruvate?

  Glycolysis
• How does cytoplasmic pyruvate enter the mitochondria?

  Utilises the ΔpH gradient
• What metabolic pathways does pyruvate link?

  Glycolysis and the TCA cycle
• What is the relevance of reprofiling alpha keto acids?

  Synthesising non-essential alpha amino acids
• Why is it important to regulate metabolic interconnections?

  To maintain metabolic balance and efficiency
• How are metabolic interconnections involved in diseases?

  They can contribute to conditions like diabetes
• What is the role of the Pyr/H+ transport protein?

  Transport pyruvate into mitochondria
• What happens when the Pyr/H+ transport protein is dysfunctional?

  It can initiate cardiovascular disease
• What is the primary function of the TCA cycle?

  Oxidise acetate to CO2
• What does the TCA cycle facilitate in terms of electron movement?

  Electrons move from acetate to oxygen
• What are ketone bodies produced from in the TCA cycle?

  Oxaloacetate
• How does the TCA cycle relate to non-glucose metabolism?

  It aids in synthesising non-essential amino acids
• What are the two types of metabolism that the TCA cycle is an entry point for?

  TCA cycle and oxidative phosphorylation
• How do cells generate energy indirectly through the TCA cycle?

  By producing ATP and XH2
• What does X represent in the context of the TCA cycle?

  NAD+ / NADH, H+, FAD+ / FADH2
• What is the source of acetyl CoA for the TCA cycle?

  Beta oxidation of saturated fats
• What can cause pyruvate to occur due to muscle tissue breakdown?

  Extreme exercise or oncogenic disease
• What is the process of decarboxylation of pyruvate?

  Conversion to acetic acid and CO2
• What enzyme decarboxylates pyruvate to acetate?

  Pyruvate dehydrogenase
• What type of amino acids yield pyruvate?

  Glucogenic and pyruvagenic amino acids
• How does the TCA cycle relate to amino acid metabolism?

  It is linked to amino acid metabolism in mitochondria
• What is the result of the breakdown of saturated fatty acids?

  Production of acetate/acetyl CoA
• What happens to mitochondria when exercise stops?

  Extra mitochondria are lost in three weeks
• How long does it take for performance athletes to switch to fatty acid metabolism?

  About ten minutes of exercise
• How does obesity affect the switch from carbohydrate to fatty metabolism?

  It takes longer to switch
• What is the relationship between stress and the TCA cycle?

  Stress can induce molecules affecting the cycle
• What is 4HNE?

  A breakdown product from unsaturated fatty acids
• How is 4HNE produced?

  Through non-enzymatic oxidation of fatty acids
• Why are α, β unsaturated aldehydes particularly toxic?

  They react across electrophilic double bonds
• What is the effect of elevated plasma levels of 4HNE?

  Precedes obesity and insulin resistance
• How does 4HNE affect fatty acid synthesis?

  It increases fatty acid synthesis and triglycerides
• What processes are affected by high levels of NADH in the TCA cycle?

  They slow down enzyme activity
• How does high zinc affect citrate metabolism in prostate cells?

  It inhibits the enzyme cis-aconitase
• What happens to citrate in prostate cancer?

  It is excreted in seminal fluid
• What is the relationship between zinc deficiency and prostate cancer?

  There is a deficiency in cellular zinc