Mitochondria and the TriCarboxylic Acid Cycle (TCA or Citric acid cycle) are central to energy production in eukaryotic cells! 10/8 and 10/13. Overview of intracellular metabolism What are the 4 Stages of aerobic energy production? How are mitochondrial organized inside?
Mitochondria and the TriCarboxylic Acid Cycle (TCA or Citric acid cycle) are central to energy production in eukaryotic cells! 10/8 and 10/13
1 glucose 38(sometimes36)ATP + 6 CO2
Glycolysis: goal create a net of 2 ATP + 2 pyruvate from glucose during hyper or euglycemia (use LDH only durign short term hypoxia).Gluconeogenesis: Goal reverse reactions if needed with pyruvate carboxylase, PEP kinase, F-1,6-biphosphatase ,and G-6-phosphatase and regenerate glucose for glucose dependent tissues during periods of hypoglycemia.
What do mitochondria look like? Classic View: discrete structures (sausage-like) New View: interconnected structures floating in the cytosol
The DNA found in mitochondria is entirely different from the DNA found in the nucleus and indicates that mitochondria probably evolved from a type of bacteria, amino acid sequence of the ATP synthase is well conserved across eukaryotes and prokaryotes.
Tricarboxylic Acid Cycle (TCA/Krebs Cycle) is the CENTRAL HUB for oxidation and energy production from sugars, fatty acids, and some amino acids!
TCA is called a “cycle” because the last step creates the substrate for the first step!
Acetyl-CoA is main entry molecule!
Some aa turned into Glucose (Acetyl-CoA)
Complete Oxidation of one Acetyl-CoA
@Intermediates back up into glycolysis too!@
All Reactions X2
for the oxidation of one glucose
2pyruvate2 Acetyl-CoA+2 NADH + 2H+ and2 CO2
Remember that a negative Delta G can help drive a reaction with a positive value if there is “No Membrane In Between”. This is why Delta G from the reactions in the mitochondria cannot help to drive the reactions of glycolysis in the cytosol. Although molecules such as pyruvate can “carry” the energy between different compartments.
Glycolysis Compared to Kreb CycleRemove products immediately after they are produced! ∆G= ∆G’o + 2.303 RT log(Keq) Keq= [Products]/[Reactants What intracellular substrate/product concentrations are typically maintained?
Beta-oxidation: is an enzyme pathway that oxidizes fatty acids into acetyl-CoA molecules that feed directly into TCA which produces 3 NADH, 1 FADH2 and 1 ATP for each ACETYL-CoA!
Fatty Acids:9 kcal/g Carbohydrates:4 kcal/g AminoAcids:4 kcal/g
Triglycerides + LipaseGlycerol + 3 fatty acids
C-16 palmitate8 acetyl-CoA(7cuts)Each acetyl-CoATCAX8
72 ATP + 16 ATP + 8 ATP = 96 ATP
PLUS: each time acetyl-CoA cut off the FA chain: 1NADH+1FADH2 created
Additional Energy: (7XNADH)+(7XFADH2)(7X3)+ (7X2)= 35 ATP
Total oxidation of palmitic acid to CO2= 96+35=131 (130)ATP
Compare to the 38 ATP from a single glucose molecule!
Fats create tons of ATP!
Fat utilization REQUIRES mitochondria and oxygen!
Fatty Acid Oxidation
A 16 carbon fatty acid yields
16/2= 8 acetyl-CoA
Remember: each acetyl-CoA (acetate) is sent to TCA and becomes oxidized to carbon dioxide plus 3 NADH, 1 FADH2 and 1 GTP(ATP)…assuming mitochondria are functioning and oxygen is available.
Beta-oxidation creates toxins during a diabetic crisis:
The Trick: the nicotinamide functional group either has a charge (NAD+; oxidized;low energy) or has an extra electron and proton (reduced; high energy; NADH). The Nic-ring structure stabilizes the extra electron so the energy in the electron can be transferred between molecules. NADH electrons mostly used in the mitochondria (not cytosol). Great T.Q. Recognize FADH2 and NADH structures and high/low energy states
Contrast TCA/Citric acid cycle in the mitochondria to what happens in the cytosol.
1 Glucose yields
Summary: What does the electron transport pathway look like? NADH and FADH2 feed e- into system via complex I OR II of the inner mitochondrial membrane depending on how much energy they contain.
What happens to the potential energy of the electrons as they move down the electron transport pathway to water? Where does the energy go relative to the proton pumps?
The ATP-synthase is the protein complex that synthesizes ATP!But Only If ADP, Pi, and proton gradient are in the matrix!This is the ChemiOsmotic Model for ATP Synthesis!
Outer Mitochondrial Membrane: relatively non-specific porins!How do cytosolic metabolites get inside the matrix?Inner Mitochondrial Membrane: specific transport enzymes!