Fatty Acids Flashcards

(44 cards)

1
Q

where does the acetyl CoA for fatty acid synthesis come from?

A

primarily from catabolism of carbohydrates

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2
Q

the three inputs into the acetyl CoA pool

A
  1. carbohydrates
  2. fatty acids
  3. amino acids
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3
Q

essential features of fatty acid

A

methyl terminus (omega end)
linear unbranched alkyl chain
even # of Cs
carboxylic acid group (#1)

saturated - MUFA (one double bond),PUFA (2)

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4
Q

of carbons in small, med, lrg, FA

A

Small 2-4
Medium 6-12
Long 14-20 Carbons
Very long

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5
Q

18:2delta9,12

A

18 carbons
2 double bonds at positions 9 and 12

9,12-octadecadienoic acid

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6
Q

families of fatty acids

A

(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

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7
Q

double bonds are generally ___ C apart

A

3 carbons apart

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8
Q

fatty acids used for;

A
  1. triglyceride synthesis
  2. cholesterol esters
  3. phospholipids, glycosolipids
  4. eicosanoid hormones
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9
Q

synthesis of FA is located in….

degradation of FA is located in…

A

synthesis of FA = cytosol
degradation of FA = mitochondria
(of certain tissues)

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10
Q

tissues of fatty acid synthesis

A
primary ; liver cytosol
adipose
CNS
lactating mammary gland
(all cytosol)
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11
Q

reactants and product of FA synthesis

A

8 acetyl-CoA
7 ATP
14 NDAPH

endergonic, reductive reactions

primary product; palmate

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12
Q

where do all the C for palmitate come from?

A

acetyl CoA;
from glucose (via glycolysis)
from pyruvate -> acetyle CoA (PDH)

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13
Q

source of NADPH for FA synth

A

phentose phosphate pathway, primarily

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14
Q

how does acetyl CoA get into the cytosol

A

can’t cross inner mito mem (to leave mito)

so brought out as Citrate - citrate lyase cleaves it and regenerates acetyl CoA

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15
Q

malic enzyme

A

generates NADPH in cytosol

Malate -> Pyruvate

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16
Q

when can you afford to send citrate out of mito

A

good times!

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17
Q

acetyl CoA carboxylase

A

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

  1. covalent: active deP (true of glycogen synthase too!), inactive if P; AMPK
  2. transcriptional reg, up-reg w high carb diet; via ChREBP at ChoRE
    insulin also upregs
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18
Q

AMPK

A

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

19
Q

fatty acid synthase (FAS)

A

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)

20
Q

can we make all the unsaturated fatty acids we need?

A

no. unable to insert a double bond after C10
can’t make n-6, or n-3
essential fatty acids; linoleic linolenic

21
Q

FA; elongation paired with desaturation

A

palmitic acid - elongated to-> stearic acid - desaturated -> oleic acid

22
Q

the essential fatty acids

A

linoleic
linolenic

used to make substrates for eicosanoid hormone synthesis

can’t insert C=C between C10 and omega C

23
Q

fatty acid activation

A

fatty acyl-CoA synthetases
req ATP

focus; long chain FA

24
Q

LCFA activation and transfer

A
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

25
fatty acid oxidation
palmitine -> Acetyl CoA +7FADH2 +7NADH Rep 4-step process: 1. FAD-linked dehydrogenation 2. hydration 3. NAD-linked dehydrogenation 4. thiolytic cleavage by CoA Products: reducing equivalents & acetyl CoA ETC -> ATP -> powers gluconeogenesis to feed the tissues that dont do FA ox
26
other things that get oxidized by CoQ (ubiquinone)
reducing equivalents from fatty acid oxidation glycerol 3 phosphate shuttle dihydroorotate to OA (pyrimidine synthesis)
27
fatty acid beta oxidation, location, process
liver, muscle
28
beta-oxidation deals with FA that are...
even number of C saturated long chain unbranched
29
dealing w odd # fatty acids
remove 2C at a time -> proprionyl CoA proprionyl CoA carboxylase (biotin) -> methylmalonyl CoA methlmalonyl CoA mutase (B12) ->succinyl CoA -> TCA -> glucose in liver ONLY FA rxn that will synthesize Glucose
30
two B12 requiring rxns in the body
1. methlymalonyl CoA -> succinyl CoA methlmalonyl CoA mutase to deal w odd numbered FA ox 2. remethylation of homocystinene -> homothionine
31
dealing w unsaturated FA
need to use additional enzymes bc the process generates an intermediate that cannot be used by the hydratase
32
VLCFA
in peroxisomes via ABC transporter (no carnitine) have the synthetase to activated the VLCFA -> MCFA & acetyl CoA link with carnitine and sent to mitochondria Pathology; ABC transporter - childhood cerebral form X-ALD most severe phenotype, progresseive neurologic loss to veg state
33
dealing with branched chain fatty acid
derived from cholorophyll -> milk and meat phytanic acid -> pristanic acid (not branched) Defect= Refsum disease (phytanic acid storage disease) very rare
34
Zellweger syndrome
peroxisome biogenesis disorder defect in proteins that recognize PTS all functions of peroxisomal matrix proteins negatively affected ZS most sever of a continuum, fatal by age 1 yr
35
ketogenesis
made in liver mitochondria alternate fuel for brain - 2C CoA +2C CoA = 4C CoA - 4C CoA + 2C CoA = 6C CoA (HMG CoA) - 6C CoA - 2C CoA = 4C (acetoacetate) by lyase - 4C decarboxylated to 3C (acetone) + CO2 - 4C reduced to 4C (beta-hydroxybutyrate) KB are actually 4C, water sol, organic acids
36
ketolysis
mitochondria of non-hepatic tissues beta-hydroxybutyrate DH acetoacetate: succinyl-CoA CoA transferase thioase
37
why doesn't ketolysis occur in the liver?
liver lacks transferase, so liver can make but not use KB | moves CoA onto acetoacetate
38
Fatty acids summary
``` structural components; triglycerides percursors; eiconsinoide hormones cytosolic synthesis; ACC,FAS mito beta-oxidation; CAT-1, e-rich citrate & carnitine to solve transport issues (in synthesis and oxidation) FA elongation & desaturation in ER limits to desturation; not past C10 => EssentialFA Peroxisomal oxidation of VLCFA ```
39
of Carbons; MCFA LCFA VLACFA
MCFA - 6-12 LCFA - 14-20 VLACFA - >22
40
malate dehydrogenase rxn
OAA + NADH -> NAD+ + Malate
41
Biotin is a coenzyme for what enzyme in fatty acid synthesis? what vitamin is it from??
Acetyl CoA Carboxylase (ACC) -among other carboxylases B7
42
source of 2C units in fatty acid synethesis
malonyl CoA
43
primary FA produced
palmitic acid (16:0)
44
elongation of FA
occurs in ER (and mito) more than one enzyme req - are ER memb proteins CoA esters used start w malonyl CoA