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28 Cards in this Set

  • Front
  • Back
major source of carbon for fatty acid synthesis
dietary carbohydrates
Fatty acid synthesis
occurs primarily in the liver

also occurs in brain, kidneys, adipose tissue

components are located in cytoplasm:
enzymes, acyl carrier proteins, co-factors, reducing power, energy-ATP
citrate
supplies the carbons for fatty acid synthesis
Levels of mitochondrial acetyl CoA regulate its own synthesis
inhibits pyruvate dehydrogenase if there is too much acetyl CoA

stimulates pyruvate carboxylase if need to make more Acetyl CoA bc that makes oxaloacetate into citrate, and citrate provides carbons for FA synthesis
Regulation by INSULIN
stimulates pyruvate dehydrogenase activity to upregulate synthesis of cytosolic acetyl CoA

up regulates synthesis of malic enzyme and citrate lyase
conversion of acetyl CoA to malonyl CoA
rate limiting step of fatty acid synthesis
rate limiting step of fatty acid synthesis
catalyzed by acetyl CoA carboxylase (ACC)

converts acetyl CoA into malonyl CoA by carboxylation

ACC adds a CO2 to acetyl CoA
Acetyl CoA carboxylase
ACC
enzymatic and carrier protein functions

biotin-dependent

synthesized as an inactive protomer

subunits serve as biotin carboxylase, a transcarboxylase, and a biotin carboxyl carrier protein
Allosteric regulation of ACC
citrate and palmitoyl CoA
Phosphorylation/Dephosphorylation regulation of ACC

(hormonal regulation)
insulin
glucagon
epinephrine
Induction/repression of ACC
up-regulated by high carb/low fat diet

down regulated by low carb/high fat diet
Fatty acid elongation
occurs at fatty acid synthase complex

2 carbons of malonyl CoA sequentially added to growing fatty acyl chain to form Palmitate (16:0)

After each addition, 2 reduction rxns occur that require NADPH and an intermediate dehydration
Fatty acid synthase
large, multi-enzyme complex

composed of 2 identical dimers, each has 7 catalytic activities and an acyl carrier protein (ACP)

ACP segment has phosphopantetheine residue (PP)

two dimers arranged in head to tail conformation
PP of one is aligned with cysteinyl sulfhydryl group of another
Further fatty acid elongation
if you need chain longer than Palmitate (16C)

must "prime" or activate chain
Palmitate activated by condensing w/ CoA to form Palmitoyl CoA

elongation of chain occurs by addition of 2 Carbon fragments from Malonyl CoA

occurs on ER membrane and catalyzed by Fatty acid elongase

makes long chain fatty acids in brain
Desaturation of fatty acids
occurs in ER
requires oxygen, NADPH, and cytochrome b5

intro of double bonds to form PUFAs

fatty acyl-CoA desaturases (non-heme iron containing enzymes)

most common location of double bond is between C9 and C10
(also can be at C4, C5, C6)
Essential fatty acids
cannot be synthesized by human body

need to get them from diet
plants synthesize these

omega 3 fatty acids and omega 6 fatty acids
Examples of essential fatty acids
Linoleic acid : (18:2, double bonds at 9,12)

Linolenic acid (18:3, double bonds at 9,12,15)
Linoleic acid and linolenic acid
precursors for eicosanoids: thromboxanes, prostaglandins, leukotrienes

deficiency leads to:
poor growth, poor wound healing, and dermatitis in persons on fat free diets
Essential fatty acids required for:
synthesis of arachidonic acid (C20, in brain)

constituents of epidermal cell sphingolipds that function as skins water permeability barrier

precursor of neuronal fatty acids
EPA
eicosapentaneoic acid
DHA
docosahexaenoic acid (fish oil)

leads to optimal neuronal development in infants
Storage and Transport of Fatty Acids
FA synthesized de novo or taken in diet-->converted to triacylglycerols (TAG)
TAG

triacylglycerols
major storage form of fuel
Synthesis of VLDL
TAG packaged with apoproteins to form VLDL

secreted in blood by liver via exocytosis
VLDL
made of TAG, cholesterol, apoproteins
Regulatory factors released by adipose tissue
Leptin and adiponectin

(adipose tissue is hormonally active)
Leptin
released when TAG levels are high
released into blood, travels to brain and mainly hypothalamus

binds to receptors, releases neuropeptides, tells body that you are full
Adiponectin
abundantly secreted hormone by adipocytes

binds receptors AdipoR1 and AdipoR2

stimulates AMPK and PPARalpha

AMPK activation leads to uptake of fatty acids and glucose
PPAR leads to enhanced fatty acid uptake

However, secretion is reduced as adipocytes get larger