BCEM 393 Lecture Notes - Lecture 12: Dihydrolipoamide Dehydrogenase, Acetyl-Coa, Lipoamide
14 Jun 2018
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Bridge Reactions and Krebs Cycle
SUMMARY — GLYCOLYSIS
- 6 carbons enter the pathway as one glucose, 6 carbons exit the pathway as 2 pyruvates
- Pathway can be divided into prep and payoff phases
- Carbon is split from the one 6C unit into two 3C units
- At steady state, flux in stage 2 is 2X greater than flux in stage 1
- 2 ATP are used to prime the pathway, 4 ATP are produced; net = 2 ATP/glucose
- 2 NAD+ are converted to NADH
DOES OUR BODY STOP AT GLYCOLYSIS TO GENERATE ATP?
- No
- Glycolysis is inefficient, capturing only a fraction of the energy inherent in a glucose molecule
as ATP
- More energy can be accessed if pyruvate is completely oxidized into carbon dioxide and
water
- Cellular respiration requires oxygen
KREBS CYCLE
- Also known as the citric acid cycle or tricarboxylic acid cycle (TCA)
- The citric acid cycle is the central metabolic hub of the cell
- It is the gateway to the aerobic metabolism of all fuel molecules
- The cycle is also crucial for anabolism, serving as an important source of precursors for the
building blocks
- Glycolysis occurs in the cytoplasm, then private enters mitochondrion
PYRUVATE DEHYDROGENASE FORMS ACETYL COA FROM PYRUVATE
- PDH complex: 3 enzymes and 5 coenzymes
- Each enzyme has its own active site
- Coenzyme A and NAD+ serve as stoichioetric coenzymes, meaning that they function as
substrates and are changed and regenerated in a reaction
- Catalytic coenzymes are not permanently altered in the reaction and are not used up
- Examples: TPP, lipoamide, FAD
PYRUVATE IS OXIDATIVELY DECARBOXYLATED TO FORM ACETYL COA
- Reaction: pyruvate + CoA + NAD+ —> acetyl CoA + CO2 + NADH + H+
- Above reaction is irreversible, and acts as a point of regulation
- Commits the carbon atoms of carbohydrates to oxudation by the Krebs cycle or to the
synthesis of lipids
PDH COMPLEX
- Decarboxylation of pyruvate
- E3 regenerates lipoamide using FADH2 and NAD
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- Steps:
- 1. Decarboxylation — pyruvate combines with TPP, releases CO2 and yields hydroxyethyl-
TPP
- 2. Oxidation — The hydroxyethyl group attached to TPP is oxidized to form an acetyl group
while being simultaneously transferred to lipoamide
- 3. Transfer — The acetyl group is transferred from acetyllipoamide to CoA to form acetyl
CoA
- 4. Replenish catalytic coenzymes — Dihydrolipoamide is oxidized to lipoamide; two
electrons are transferred to FAD prosthetic group of the enzyme and then to NAD+
REGULATION OF PDH
- The formation of acetyl CoA from pyruvate is an irreversible step
- Regulated through allosteric interactions:
- Acetyl CoA inhibits the transacetylase component (E2) by directly binding to it
- NADH inhibits the dihydrolipoyl dehydrogenase (E3)
- Regulated through covalent modifications
- Phosphorylation of E1
- During high energy charge: don't need Krebs cycle running, therefore, acetyl CoA and NADH
negatively regulate production of PDH
- During low energy charge: need Krebs cycle running, therefore positively regulated by ADP
and precursor of pryruvate
WHEN ENERGY IS NEEDED AND O2 IS PRESENT…
- 2 carbons enter the pathway as one Acetyl CoA
- Carbon is recycled via a continuous series of reactions
- Enables most of the energy in glucose to be captured via redox reactions
- Functions to harvest high-energy electrons that will be used to power the synthesis of ATP
NET OUTCOME OF THE KREBS CYCLE
- 2 cabrons enter the pathway as one Acetyl CoA, 2 carbons exit the pathway as 2 CO2
- 1 GTP is produced via substrate-level phosphorylation
- 3 NAD+ are converted to 3 NADH
- 1 FADH2 is produced
- Oxaloacetate is regenerated allowing continued functioning of the cycle
- Need continuous supply of acetyl CoA for Krebs cycle to keep running
STEP 1: CITRATE SYNTHASE
- Acetyl CoA (C2) condenses with oxaloacetate (C4) to yield citrate (C6)
- Condensation reaction, irreversible
- ∆G°’ = -32.2 kJ/mol
- Reaction: Oxaloacetate + Acetyl CoA —> Citryl CoA + H2O —> Citrate + CoA
STEP 2: CITRATE IS ISOMERIZE TO ISOCITRATE
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
6 carbons enter the pathway as one glucose, 6 carbons exit the pathway as 2 pyruvates. Pathway can be divided into prep and payoff phases. Carbon is split from the one 6c unit into two 3c units. At steady state, flux in stage 2 is 2x greater than flux in stage 1. 2 atp are used to prime the pathway, 4 atp are produced; net = 2 atp/glucose. Glycolysis is inefficient, capturing only a fraction of the energy inherent in a glucose molecule as atp. More energy can be accessed if pyruvate is completely oxidized into carbon dioxide and water. Also known as the citric acid cycle or tricarboxylic acid cycle (tca) The citric acid cycle is the central metabolic hub of the cell. It is the gateway to the aerobic metabolism of all fuel molecules. The cycle is also crucial for anabolism, serving as an important source of precursors for the building blocks.
