Fatty Acid Metabolism Flashcards
where does synthesis of fatty acids occur?
liver, adipose tissues and mammary glands are the main sites
Can all fatty acids be synthesized?
All except C18:2 and C18:3
what is the substrate for synthesis of fatty acids?
acetyl CoA
What is acetyl CoA carboxylated to? what is this catalyzed by?
Malonyl CoA, catalyzed by acetyl CoA carboxylase
the step wise addition of 2- carbon molecules to a growing chain is catalyzed by what?
multifunctional enzyme “fatty acid synthase”
what are the steps in synthesis of fatty acids?
- glucose enters liver cells and is converted to pyruvate (glycolysis)
- pyruvate enters the mitochondria and is converted to acetyl- CoA by pyruvate dehydrogenase and to oxaloacetate by pyruvate carboxylase
- acetyl-CoA and oxaloacetate condense to form citrate which leaves the mitochondria
- in cytosol, citrate is cleaved to oxaloacetate and acetyl-CoA by citrate lyase (requires ATP + induced by insulin)
- acetyl CoA is converted by acetyl CoA carboxylase to malonyl CoA
- growing fatty acyl chain on the fatty acid synthase complex is elongated, 2-carbons at a time by the addition of the 3-carbon compound malonyl CoA which is decarboxylated
- palmitate is converted to other fatty acyl CoAs by elongation and desaturation
- the fatty acyl-CoA combines with glycerol-3-p to form triacylglycerols by a pathway in which phosphatidic acid serves as an intermediate
- triacylglycerols packaged in VLDL are secreted into blood
which enzyme cleaves citrate to oxaloacetate and acetyl CoA? what does it require?
Citrate lyase it uses ATP
which enzyme converts pyruvate to acetyl-CoA?
Pyruvate Dehydrogenase
which enzyme converts pyruvate to oxaloacetate?
Pyruvate Carboxylase
which enzyme converts Acetyl-CoA to malonyl CoA?
Acetyl CoA carboxylase
fatty acid synthase requires _______ to reduce the growing chain
NADPH
where does the NADPH come from?
from the pentose phosphate pathway
what is the product released by fatty acid synthase complex?
Palmitate
fatty acyl CoA combines with what to form triacylglycerols?
Glycerol-3-Phosphate
how do triacylglycerols get into the blood?
they are packaged in VLDL
what inhibits Fatty acid synthase?
Epinephrine, glucagon inhibit PP2A (protein phosphatase 2A)
what reactivates acetyl-CoA carboxylase?
Insulin through stimulation of PP2A which reactivates acetyl-CoA carboxylase and citrate stimulates acetyl-CoA carboxylase
What inhibits Acetyl CoA carboxylase?
Palmitoyl-CoA
what are the sources of fatty acids?
- de novo synthesis
- hydrolysis of cellular triglycerides
- fatty acids from circulation
What pathways synthesizes triglycerides: Fatty acid + ATP –> Fatty acyl CoA + AMP
mainly Glycerol-3-phosphate pathway
what mediates fat mobilization?
hormone sensitive lipase (HSL)
what process regulates HSL ?
phosphorylation-dephosphorylation process
In what state is HSL dephosphorylated by insulin (inactivation)?
the fed state
What happens to HSL in the fasting state?
HSL is phosphorylated by epinephrine and norepinephrine
HSL changes triacylglycerol to what?
triacylglycerol–> glycerol + 3 fatty acids
What is another word for catabolism of fatty acids?
ß-oxidation
where does B-oxidation occur?
in the mitochondria to generate energy
why do fats generate more energy?
because they exist in more reduced form of CHO
when is oxidation of fatty acids high? why?
During the starvation state due to increased concentrations of fatty acids in blood
what is the first step in B-oxidation?
synthesis of fatty acyl CoA in the cytosol by fatty acyl CoA synthetase
what mediates the transport of fatty acyl CoA into the mitochondria?
Carnitine
which fatty acids produces more energy? unsaturated fatty acids or saturated fatty acids?
Saturated fatty acids produce more energy
during what state is acetyl-CoA from B-oxidation, oxidized to CO2 and water in TCA cycle?
the well **fed **state
what does the liver convert during the starvation state?
the liver converts acetyl CoA to ketones (acetoacetate & B-hydroxybutyrate)
what are ketone bodies used for?
used for fuel source (energy) by extrahepatic tissues (not the liver)
which produces more energy: fatty acids or ketone bodies?
ketone bodies produce less energy than fatty acids
when might a person have high blood concentrations of ketone bodies?
diabetes, starvation or very low CHO diet
what inhibites carnitine acyl transferase?
Malonyl CoA
Hypoglycemia (low blood sugar= glucose) _________ lipolysis in some cases ketone body formation
STIMULATES
HSL is inactivated by what hormone?
INSULIN
_____ glucose level and ______ insulin level favors lipolysis.
**LOW, ** LOW
HSL is activated by which hormones?
epinephrine and norepinephrine
what stimulates synthesis of acetyl CoA?
Citrate
What is atherosclerosis?
it is a degenerative disease of vascular endothelium
what happens in atherosclerosis?
- accumulation of cholesterol and cholesterol esters blocks capillaries causing them to tear up,
- recruitment of immune cells: cytokines, macrophages, monocytes and T lymphocytes accumulate.
- LDL is uptaken by phagocytic cells and an increased deposition of lipids in blood vessels (fatty plaque)
what is associated with a high amount of LDL ?
high fat diet + high cholesterol+ cholesterol esters
what are the main lipid risk factors for Cardiovascular disease?
- Cholesterol
- Saturated and Unsaturated fatty acids
- Trans fatty acids
how can risk of CVD be reduced?
by maintaining a low LDL : HDL ratio
Apo A: Apo B can be a measure of what?
Cardiovascular disease risk ApoB= LDL ApoA=HDL
What type of fatty acids are HYPOcholesterolemic (low lvls)?
Unsaturated fatty acids (double bonds)
what type of fatty acids are HYPERcholesterolemic (high lvls)?
Saturated fatty acids
which fatty acid is neutral?
C18:0
Plant PUFA are ____ effective than marine PUFA
LESS
why can saturated fatty acids be associated with a high risk of cardiovascular disease?
- they suppress bile acid excretion
- increase synthesis of choleserol + LDL
- reduce uptake of LDL
trans fatty acids come from partial hydrolysis of what?
Polyunsaturated fatty acids (PUFA)
what is the most abundant trans fatty acid?
Elaidic acid (C18:1 FA) and isomers
trans fatty acids are ______ cholesterolemic
HYPER = high levels of cholesterol
which one is more detrimental, saturated fatty acids or trans fatty acids?
Trans fatty acids
Trans is _______ than Cis
WORSE
as LDL + total cholesterol increases, HDL ________.
decreases
