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Synthesis
of Backbone of^ TAGs +^ Phospholipids
Most glycerol 3-phosphate comes from siphoning off dihydroxyacetone phosphate (DHAP) from^ glycolysis
va glycerol 3-phosphate dehydrogenase Glucose
some glycerol 3 phosphate is made from glycerol
glycolysis,
Vla glycerol kinase
H2COM HeCOM
minor (^) pathway in liver + kidney (^6) =0 o^ I
MCON
II I
fatty acy/group is^ activated^ by formation^ of^ the^ fatty^ acyl-CoA^ M2-0-p-o- HzCOM
then transferred to ester linkage with L-glycerol 3.phosphate, Dihydroxyacetoned-
Glycerol
Phosphatidic acid^ (2) a+^ c-2^ of^ the^ glycerol molecule.^ Intermediate^ phosphate
productwith^ only one^ esterified^ fatty^ acyl group is^ lysophosphatidic
m +
acid. To conserve space in subsequentfigures,both fatty acyl groups of
glycerols-pnosprate), )
Meet (^).
glycerophospholipids, i
I all three acyl groups of triacylglycerols are dehydrogenase
shown projecting to^ the^ right. NADI
Synthesis of^ Phosphophatidic^
Acid
I
4,c-0-1 - 0 - Occurs before^ TAGS^
i
Phosphatidic acid^ ->^ precursor to^ TAGs^ + phospholipids
-Glycerol 3-phosphate
fatty acids^ attached^ by acyltransferases H2COH
releases CoA notto
L-Glycerol 3-phosphate
Advantage of^ making phosphatidic^ acid:^ R^ - c00-
Itcan then be made into triacylglycerol OR phospholipid
Phosphatidic Acid^ can^ be^ modified^ to
I
)*areene
form (^) phospholipids or TAGS
4 - R Phosphatidic acid phosphatase (lipin) removes
attachment of the (^) 3-phosphate from the (^) phosphatidic acid a (^) cyl transferase
roro
are
intrcm? re
Phosphatein
3rd carbon is then acylated with a^ 3rd^ fatty acid^ acyltransferase^ I
yields 1,2-diacylglycerol (^12) anden^ yields (^) triacylglycerol COA-SH
icanincinaraareainconosphatidis
acid is the (^) precursor of both (^) triacylglycerine 2 - oh
- r_-k^ Glycerophospholipids,^ glycerophospholipids.^ Mechanisms^ for^ head^ group isnote
re
attachment in phospholipid synthesis (^) 0- Phosphatidic add
Regulation
of Triacylglycerol Synthesis by Insulin
Insulin results in stimulation of^ triacylglycerol Synthesis Dietary Pletary
carbohydrates proteins
Lack of^ insulin^ results^ In: Increased ↓^ ↓
lipolysis
Increased Glucose^ Amino^ acids
fatty acid^ oxidation
sometimes to ketones if citric acid cycle intermediates
coxaloacetate) thatreactwith acetyl CoA are depleted
insulin--->()
failure to synthesize fatty acids
! Acetyl-CoA^ ---> increased^ -> Retonebodies
Insulin stimulates conversion ofdietary carbohydrates + proteins to^ fat. ... - - (acetoacetate,
In diabetes p-B-hydroxybutyrate,
Individuals with diabetes mellitus either lack^ insulin^ or are acetone)
fatty acids
sensitive to it. This results in diminished (^) fatty acid (^) synthesis + ↓
acetyl-CoA arsing from^ catabolism^ of^ carbohydrates + proteins
Triacylglycerols
is shunted Instead to ketone body production. People In
severe ketosis smell of^ acetone,so^ the^ condition^ is^ Triacylglycerol Breakdown+Resynthesis sometimes mistaken for^ drunkenness^ create a^ futile^ cycle Triacylglycerol Cycle^ 75%^ of^3 fatty acids^ (ffAs)^ released^ by lipolysis are^ re-esterified Adipose tissue Blood Liver to form TAGs,rather than be used for fuel Lipoprotein
Glycerol"pase
Elycerol Some^ recycling occurs^ in^ adipose^ tissue
A M Some^ FFAs^ from^ adipose^ cells^ are^ transported^ to^ the^ liver,
Triacylglycerol Fatty Triacylglycerol remade into TAG, and redeposited in adipose cells.
- I (^) Although distribution^ between^ the^2 paths (^) may vary overall, Glycerol Fuel for Glycerol
3-phosphate + ISSUES 3-phosphate the^ percentage of^ FFAs being esterified^ remains^ at75%
Pyruvate
Mammals ->triacylglycerol molecules broken down tresynthesized ↓ pyruvate carboxylase Glyceroneogenesis
oxaloacetate (^) Lipolysis -> stimulated (^) by glucagon or (^) epinephrine
during starvation.^ Some^ fatty pods^ released^ by^ lipolysis^ of
↓^ Pep^ carboxykinase^ Iglycolysis^ Is^ Inhibited)
triacylglycerol in^ adipose^ tissue^ pass^ Into^ bloodstream.^ Remainder^ is^ Phosphoenolpyruvate^ DHAP^ is^ not readily available^ to^ make^ glycerol
used for resynthesis of triacylglycerol.Some fatty acids released ↓^ multistep^3 phosphate
Dihydroxyacetone phosphate (^) Adipose cells don'thave (^) glycerol kinase into the blood are used for (^) energy (In (^) muscle) + some are taken ↓^ glycerol^
- phosphate to make (^) glycerol 3 phosphate on site
up by the^ liver^ +^ used^ in^ triacylglycerol synthesis. The^ triacylglycerol H2C-OH^ dehydrogenase^ contains^ similar^ steps^ of^ gluconeogenesis
formed (^) in the liver is transported in the blood back to adipose (^) tissue, ric-on^9 Converts^ pyruvate^ -> (^) DHAP an abbreviated version of (^) gluconeogenesis where the (^) fatty acid is^ released^ by extracellular^ lipoprotein lipase (^) mac no rate In^ the^ liver^ +^ adipose^ tissue
taken up by adipocytes + reesterified into triacylglycerol
Triacylglycerol (^) synthesis
