Lecture 5 Production of Acetyl-CoA Flashcards
What is cellular respiration?
Catabolism of substrates which are oxidized to CO2 and H2O, in the presence of oxygen.
- A set of metabolic reactions and processes that take place in the cellular mitochondria to convert chemical energy from oxygen molecules or nutrients into adenosine triphosphate, and then release waste products.
Range of carbon oxidation states
Carbon can exhibit oxidation states ranging from
-4 (methane: CH4) to 0 (glucose: (CH2O)6) to +4 (carbon dioxide: CO2)
What oxidation happens to carbon and oxygen during cellular respiration?
- carbon atoms are oxidized to CO2 (oxidation state = +4)
- molecular oxygen (oxidation state = 0) is reduced to H2O (oxidation state of oxygen = -2).
Stages of cellular respiration
Stage 1: Formation of acetyl-CoA from glucose, fatty acids and some amino acids.
Stage2: Oxidation of acetyl-CoA by the citric acid cycle and generation of NADH and FADH2.
Stage 3: Oxidation of the NADH and FADH2 by the electron transfer chain coupled to ATP synthesis.
Where does pyruvate form into AcetylCo-A?
Occurs in the mitochondrial matrix
Anatomy of the mitochondria
What are the 4 compartments of the mitochondrial matrix and role in cellular respiration?
- Outer membrane → Has transmembrane channels called porins which are permeable to molecules <5 kDa
- Inner membrane → essentially impermeable so selective and requires transporters; ETC enzymes found here
- Intermembrane space → between outer and inner membrane; contains cytochrome c
- The matrix → inside inner membrane; contains many oxidative enzymes systems such as the PDH complex and citric acid cycle enzymes
How does pyruvate move from the cytosol into the mitochondrial matrix?
- diffuses through the outer membrane via porin
- Transported through the inner membrane with a proton via pyruvate translocase
- Once in the matrix, the pyruvate dehydrogenase complex oxidizes pyruvate to acetyl-Coenzyme A
Reaction of pyruvate → acetyl-CoA
Oxidative decarboxylation via pyruvate dehydrogenase
- practically irreversible
- exergonic → ∆G’o= -33.4 kJ mol-1
Structure of AcetylCo-A
Acetyl-CoA is an acetyl group in thioester bond with coenzyme A.
- Coenzyme A contains pantothenic acid (vitamin B5) and mercaptoethylamine whose sulfhydride is in thioester bond with acetate.
- Also contain an ADP
What part of AcetylCo-A makes it high energy?
The thioester linkage is a “high energy” bond, which is particularly reactive.
- Hydrolysis of this thioester bond is exergonic.
What does Coenzyme A function in?
Acyl group transfer reactions.
What is the PDH complex composed of?
Pyruvate dehydrogenase
3 enzymes (E1, E2, E3) and requires 5 cofactors.
What are the 3 enzymes of PDH?
- E1: pyruvate dehydrogenase
- E2: dihydrolipoyl transacetylase
- E3: dihydrolipoyl dehydrogenase
What are the cofactors of PDH and their location and function?
- thiamine pyrophosphate (TPP)
- lipoic acid
- coenzyme A(CoA)
- flavin adenine dinucleotide (FAD)
- nicotinamide adenine dinucleotide (NAD+)