Fatty Acids Flashcards

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
Q

fatty acid oxidation

A

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
Q

other things that get oxidized by CoQ (ubiquinone)

A

reducing equivalents from
fatty acid oxidation
glycerol 3 phosphate shuttle
dihydroorotate to OA (pyrimidine synthesis)

27
Q

fatty acid beta oxidation, location, process

A

liver, muscle

28
Q

beta-oxidation deals with FA that are…

A

even number of C
saturated
long chain
unbranched

29
Q

dealing w odd # fatty acids

A

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
Q

two B12 requiring rxns in the body

A
  1. methlymalonyl CoA -> succinyl CoA
    methlmalonyl CoA mutase
    to deal w odd numbered FA ox
  2. remethylation of homocystinene -> homothionine
31
Q

dealing w unsaturated FA

A

need to use additional enzymes bc the process generates an intermediate that cannot be used by the hydratase

32
Q

VLCFA

A

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
Q

dealing with branched chain fatty acid

A

derived from cholorophyll -> milk and meat

phytanic acid -> pristanic acid (not branched)

Defect= Refsum disease (phytanic acid storage disease) very rare

34
Q

Zellweger syndrome

A

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
Q

ketogenesis

A

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
Q

ketolysis

A

mitochondria of non-hepatic tissues

beta-hydroxybutyrate DH
acetoacetate: succinyl-CoA CoA transferase
thioase

37
Q

why doesn’t ketolysis occur in the liver?

A

liver lacks transferase, so liver can make but not use KB

moves CoA onto acetoacetate

38
Q

Fatty acids summary

A
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
Q

of Carbons;
MCFA
LCFA
VLACFA

A

MCFA - 6-12
LCFA - 14-20
VLACFA - >22

40
Q

malate dehydrogenase rxn

A

OAA + NADH -> NAD+ + Malate

41
Q

Biotin is a coenzyme for what enzyme in fatty acid synthesis? what vitamin is it from??

A

Acetyl CoA Carboxylase (ACC)
-among other carboxylases

B7

42
Q

source of 2C units in fatty acid synethesis

A

malonyl CoA

43
Q

primary FA produced

A

palmitic acid (16:0)

44
Q

elongation of FA

A

occurs in ER (and mito)
more than one enzyme req - are ER memb proteins
CoA esters used
start w malonyl CoA