Fatty Acids Flashcards
(44 cards)
where does the acetyl CoA for fatty acid synthesis come from?
primarily from catabolism of carbohydrates
the three inputs into the acetyl CoA pool
- carbohydrates
- fatty acids
- amino acids
essential features of fatty acid
methyl terminus (omega end)
linear unbranched alkyl chain
even # of Cs
carboxylic acid group (#1)
saturated - MUFA (one double bond),PUFA (2)
of carbons in small, med, lrg, FA
Small 2-4
Medium 6-12
Long 14-20 Carbons
Very long
18:2delta9,12
18 carbons
2 double bonds at positions 9 and 12
9,12-octadecadienoic acid
families of fatty acids
(n-reference = omega-reference)
n = # of carbons
n-6;
18-6 = first double bond is 12 C in from the carboxylic end or methyl terminus
double bonds are generally ___ C apart
3 carbons apart
fatty acids used for;
- triglyceride synthesis
- cholesterol esters
- phospholipids, glycosolipids
- eicosanoid hormones
synthesis of FA is located in….
degradation of FA is located in…
synthesis of FA = cytosol
degradation of FA = mitochondria
(of certain tissues)
tissues of fatty acid synthesis
primary ; liver cytosol adipose CNS lactating mammary gland (all cytosol)
reactants and product of FA synthesis
8 acetyl-CoA
7 ATP
14 NDAPH
endergonic, reductive reactions
primary product; palmate
where do all the C for palmitate come from?
acetyl CoA;
from glucose (via glycolysis)
from pyruvate -> acetyle CoA (PDH)
source of NADPH for FA synth
phentose phosphate pathway, primarily
how does acetyl CoA get into the cytosol
can’t cross inner mito mem (to leave mito)
so brought out as Citrate - citrate lyase cleaves it and regenerates acetyl CoA
malic enzyme
generates NADPH in cytosol
Malate -> Pyruvate
when can you afford to send citrate out of mito
good times!
acetyl CoA carboxylase
1
acetyl CoA +CO2 +ATP -> malonyl CoA (3Cs)
biotin is essential coenzyme (caroboxylases req it)
committed, rate-lim, regulated:
1. allosteric;
+citrate
-endprod-palmitic acid
- covalent: active deP (true of glycogen synthase too!), inactive if P; AMPK
- transcriptional reg, up-reg w high carb diet; via ChREBP at ChoRE
insulin also upregs
AMPK
AMP-activated protein kinase
rise in AMP:ATP ratio
major distress signal; hypoxia, exercise
AMP - most sensitive indicator of cell’s e state
P’lates acetyl CoA carboxylates = inhibits it
fatty acid synthase (FAS)
homodimeric, multifunctional (7 catalytic domain + aceyl carrier protein domain - the swinging arm)
Adds 2Cs from malonyl CoA to carboxylate end of an Acyl acceptor
How; rep seq of condense, reduce, dehydrate, reduce
NADPH used from PPP + malic enzyme
Primary Product; Palmite (16:0)
*shorter FA are possible - mothers milk
methylmalonyl CoA -> branched FA (plants)
can we make all the unsaturated fatty acids we need?
no. unable to insert a double bond after C10
can’t make n-6, or n-3
essential fatty acids; linoleic linolenic
FA; elongation paired with desaturation
palmitic acid - elongated to-> stearic acid - desaturated -> oleic acid
the essential fatty acids
linoleic
linolenic
used to make substrates for eicosanoid hormone synthesis
can’t insert C=C between C10 and omega C
fatty acid activation
fatty acyl-CoA synthetases
req ATP
focus; long chain FA
LCFA activation and transfer
activation in cytosol crosses the outer membrane Carmitine palmitoyl transferase 1 (CPT 1) removes the CoA -> Fatty acylcarnitine crosses the inner membrane Carnitine removed
Regulated, Rate limiting step
Malonyl CoA inhibits CAT-1 (synthesis of FA prevents FA oxidation)
SCFA MCFA are activated w/in the matrix