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Biochemistry- Unit Two
Generation of Acetyl CoA (T Pierce)
27
Medical
Post-Graduate
04/03/2009

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Cards

Term
Sources of Acetyl CoA
Definition
  • pyruvate via pyruvate dehydrogenase
  • Fatty acids via beta oxidation
  • ethanol
  • ketone bodies
  • ketogenic AA's
Term

How does pyruvate get into mitochondrial matrix?

Definition
pyruvate translocase (antiport with H+)
Term
Sources of pyruvate
Definition
  • glycolysis
  • transamination of Ala
  • deamination of Ser, Cys
Term
What makes up pyruvate DH complex
Definition
  • decarboxylase- eliminates CO2
  • transacetylase- adds CoA onto acetyl
  • dihydrolipoyl dehydrogenase- reduces NAD to NADH
Term
Function of fattyl acyl CoA synthetase
Definition
  • converts FA to FA-CoA via ATP hydrolysis to AMP + PP (specific for short, medium, and long chain FA's)
  • PPi will be made into 2 P via pyrophosphatase (makes rxn irreversible)

 

Term

Location of fatty acyl CoA synthetases

Definition
  • outer mit. membrane
  • ER membrane
  • peroxisome
Term

Describe Dietary need for carnitine

Definition
there is no dietary need; we can make all the carnitine we need
Term
Steps in carnitine transferase
Definition
  1. at outer mitochondrial membrane, fatty acyl-CoA combine with carnitine to create fatty acyl-carnitine and CoA via ATPase
  2. fatty acyl-carnintine move out via translocase antiport with carnitine
  3. in mitochondrial matrix, FA is transfered back to CoA to make fatty acyl-CoA via fatty acyl-CoA carnitine transferase II
Term

Steps in beta oxidation

Definition
  1. fatty acyl-CoA converted to enoyl CoA and creates  FADH2 via fattyl acyl-CoA dehydrogenase
  2. enoyl-CoA and water form beta hydroxylacy-CoA via enoyl-CoA hydratase
  3. beta hydroxyacyl-CoA converted to beta ketoacyl-CoA and NADH via beta hydroxyacyl-CoA dehydrogenase
  4. beta hydroxyacyl-CoA and CoA-SH combine to form acetyl CoA and fatty acyl-CoA (LOST TWO CARBONS) via beta keto thiolase
Term
Overall products of beta oxidation
Definition

1 NADH

1 FADH2

1 acetyl CoA

1 fatty acyl-CoA (two carbons shorter)

Term
Eventually, if we keep going through beta oxidation on one fatty acid, when we get to a four carbon chain, how does this change are products
Definition
instead of a fatty acyl Coa, we would get two acetyl-CoA's
Term
Equation to find out number of acetyl CoA's produced by even numbered FA's as well as the number of sequences
Definition

#C/2 = #acetyl-CoA

#C/2-1 = # sequences

Term
Effect of every double bond present on the end products of beta oxidation
Definition
there is one less flavoprotein (there is already a double bond there, so we can oxidize)
Term
Fate of odd numbered FA's in beta oxidation
Definition
continue breaking down until you form acetyl CoA and propionyl CoA (cant undergo beta oxidation)
Term
Steps of metabolism of propionyl-CoA
Definition
  1. via propionyl-CoA carboxylase hydrolysis of ATP (coenzyme: biotin), add CO2 to propionyl-CoA producing ADP/P and methyl malonyl-CoA
  2. methyl malonyl-CoA converted to succinyl CoA via methyl malonyl-CoA mutase (coenzyme: Adenosyl-B12)
    1. moves carboxyl groop to end of chain
Term
Cause of methyl malonic aciduria?
Definition
  • if you are deficient in adenoyl-B12 (coenzyme for methyl malonyl-CoA mutase), causes a build up in methyl-malonyl-CoA
  • leads to ties up CoA
  • if CoA tied up, it decreases
  • if it decrease, we decrease beta oxidation
  • however, body hydrolyzes off CoA it to methyl malonic acid that is excreted in the urine
Term
Location of enzymes in propionyl CoA path
Definition
mitochondrial matrix
Term
What type of FA's tend to undergo beta oxidation in the peroxisome membrane?
Definition

very long chain FA's (more than 22 C's)

Term

Unique features of peroxisome beta oxidation

Definition
  • instead of using a dehydrogenase to produce enoyl CoA and FADH2, we use the oxidase (produces peroxide from oxygen)
  • beta oxidation stops at C8: octanoyl-CoA
  • the end products: octanoyl-CoA and acetyl-CoA
    • both use transferases to convert to octanoyl-carnitine and acetyl-carnitine
      • produces CoA-SH
    • both can now move into mitochondrial matrix where oxidation is complete
Term
Name major ketone bodies
Definition
  • acetoacetate
  • acetone (breakdown product of removing carboxyl group from acetoacetate)
  • beta hydroxybutyrate
Term

During what body state are ketone bodies made?

Definition
during starvation (36-48 hrs)
Term
Where are ketone bodies made in the body? what is there fate after that?
Definition
  • produced in the liver
  • released into blood
  • taken up by tissues (ex: heart, muscle, brain) and oxidized to CO2 as an energy source
Term
Clinical application- effect of build up of acetone
Definition
  • breath will smell like finger nail polish removal
  • seen in type I diabetes that is not treated (classic ketoacidosis)
Term
Function of beta hydroxybutyrate dehydrogenase
Definition
oxidize beta HOB to acetoacetic acid
Term

Oxidation rxn of ketone bodies starting from Beta HOB

Definition
  1. beta hydroxybutyric acid oxidized to produce acetoacetic acid and NADH via beta hydroxybutyric acid dehydrogenase
  2. acetoacetic acid and succinyl-CoA combine to form succinate and acetoacetyl-CoA via transferase
  3. acetoacetyl-CoA combine with CoA-SH produce two acetyl-CoA's via thiolase
  4. acetyl-CoA go into TCA cycle
Term
location of ketone body oxidation in cell
Definition
mitochondrial matrix
Term
Number of ATP's produced from beta-HOB? acetoacetate?
Definition
  • acetoacetate- 20 ATP's (2 acetyl CoA's)
  • beta hydroxybutyrate- 22.5 ATP's (2 acetyl CoA's and NADH)
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