Lecture 8 - Fatty acid oxidation Flashcards
State the length classification for FAs.
- Very long > 20
- Long 12 - 20
- Medium 6 - 12
- Short
Explain the general movement of FA oxidation overnight.
1) Adipose cells release long chain FAs
2) Circulate in blood associated with albumin
3) In cells are converted to Fatty acyl-CoA by acyl-CoA synthetase
4) Activated acyl-CoA transported into matrix bound to carnitine
5) Fatty acyl-CoA regenerated in beta ox
6) Oxidizing produces FADH2, NADH, and Acetyl-CoA (all require oxidative phosphorylation to produce ATP)
Where are water-soluble, medium chain FAs oxidized?
Do not require carnitine and occurs only in liver
What rxn occurs to excess FAs? What are the products and where do the products of this rxn end up?
Gamma-oxidation, dicarboxylic acid products end up in urine
Where are very long FA chains processed prior to entering the mitochondria?
Peroxisomes
What are acetoacetate and beta-hydroxybutyrate and where are they generated?
Ketone bodies, liver
What is the role of Malonyl-CoA?
Inhibits formation of fatty acyl carnitine derivatives
Stearic acid
C18 (18 carbons including the carbon of the carboxylic acid)
Oleic acid
C18:1 (18 carbons including the carbon of the carboxylic acid + one double bond)
Linolenic acid
C18:3
Arachidonic acid
C20:4
Role of acyl CoA synthetase
Activates FA using ATP. Forms a transient covalent bond with a phosphate in order to allow CoASH to perform nucleophilic attack.
Where are the acyl-CoA isozymes required to activate short chain FAs located?
Cytosol or on mitochondrial membrane
Where are the acyl-CoA isozymes required to activate medium chain FAs located?
Matrix of mitochondria
Where are the acyl-CoA isozymes required to activate long chain FAs located?
Endoplasmic reticulum, outer mitochondrial membrane, or peroxisomal membranes
Where are the acyl-CoA isozymes required to activate very long chain FAs located?
In peroxisomes
Where is carnitine located? What is its role at this location?
External and internal surfaces of the inner mitochondrial membrane, Shuttles fatty acyl CoA into the matrix.
List the enzymes in the beta oxidation spiral in order.
1) Acyl CoA dehydrogenase, enoyl CoA dehydrogenase, beta hydroxy acyl CoA DH, beta-keto thiolase
(ACDH, ECDH, BHACDH, BKT)
Palmitic acid
C16
List the substrates of the FA oxidation spiral.
1) Fatty acyl CoA
2) Trans ^2 fatty enoyl CoA
3) L-beta-hydroxy acyl CoA
4) Beta-keto acyl CoA
What is the role of enoyl CoA isomerase?
Turns a cis unsat bond to a trans (moves it towards the acyl coA end)
What is the enzyme that solves the problem of a conjugated trans and cis double bond?
2,4-dienoyl-CoA reductase (step oxidizes NADPH to NADP+ and creates trans fat between sites of original double bonds). NOTE: this creates an beta trans bond which cannot be handled by 3-L-hydoxyacyl DH
What enzyme corrects the problem created by 3,2-dienyoyl-CoA isomerase (a beta trans bond)?
3,2-dienoyl-CoA reductase
What type of oxidation is required for branched FAs
Alpha oxidation
Where does omega oxidation occur?
ER
What does omega oxidation of FAs produce?
Dicarboxylic acids (observed in urine if defects in beta ox)
What is the effect of low insulin/high glucagon on beta ox?
Activates hormone sensitive lipase > increased FAs
Where are ketone bodies synthesized?
Liver mitochondrion
What enzyme required for conversion of ketones back to acetyl-CoA is absent in the liver? What does this enzyme do?
Succinyl CoA: acetoacetyl CoA transferase - transfers a CoASH to acetoacetate
State the enzymes in order that convert beta-hydroxybutyrate to 2 acetyl-CoA.
1) Beta-hydroxybutrate DH
2) Succinyl CoA:acetoacetyl CoA transferase (thiophorase)
3) Thiolase
How many ATP do acetoacetate and beta-hydroxybutyrate produce?
acetoacetate: 19 beta-hydroxybutyrate: 21.5
What tissues can only use glucose?
RBC, Renal medulla
