BB451 exam 2 - Fatty Acid Metabolism Flashcards
fats stored in
adipocytes
fatty acids travel in blood stream by…
serum albumin
degradation (summary)
in mitochondria and peroxisome
oxidation, hydration, oxidation, cleavage
synthesis (summary)
in cytoplasm and ER and mitochondrion
reduction, dehydration, reduction, condensation
lipases
break down fats to fatty acids and glycerol
glycerol
only part of fat that can be made into glucose (via gluconeogenesis)
across intestine wall…
monoacylglycerol + fatty acids –> across wall
then reassembled and go to chylomicrons
triacylglycerol lipase
hormone sensitive
only regulated enzyme of fat or fatty acid breakdown
in adipocytes
cute first one off?
oxidation in mitochondrial matrix
in cells: fatty acids attached to CoA (acyl-CoA)
at mitochondria: CoA replaced by carnitine
in matrix: carnitine replaced by CoA again
steps in beta oxidation mirror…
oxidation of succinate to oxaloacetate in CAS
step 1 beta oxidation
dehydrogenation
enzyme: acyl-CoA dehydrogenases
- -> FADH2 and intermediate w/ double bond in trans
step 2 beta oxidation
hydration: add water across double bond
- -> hydroxyl group on 3rd C from CoA in L form
step 3 beta oxidation
oxidation –> NADH and ketone
step 4 beta oxidation
thiolytic cleavage
catalyzed by thiolase : cleave off acetyl CoA –> fatty acyl-CoA with 2 fewer Cs
thiolase
catalyzes thiolytic cleavage (step 4 in beta oxidation)
acyl-CoA dehydrogenase
catalyzes dehydrogenation (step 1 in beta oxidation) specialized form for long, medium, and short chain fatty acids pulls out protons and e's between C2-3
short and medium chain acyl-CoA dehydrogenases ….
in mitochondria
short : 8-10 or smaller
medium - some instances of sudden infant death syndrome if deficient
long chain acyl-CoA dehydrogenases
in peroxisomes (>16C) e to oxygen --> hydrogen peroxide instead of FADH2 (less efficient)
most common fatty acid
palmitic acid / palmitoyl - CoA
16 carbons
cycle 7 times –> 8 acetyl CoAs
enoyl -CoA - isomerase
converts cis (or trans) bonds between 3-4 to trans between 2-3
beta oxidation normally has ___ bonded intermediates between __
trans bonds intermediates between 2-3
2,4 - dienoyl - CoA reductase
acts on intermediates that have double bonds between 2-3 and 4-5.
uses NADPH to reduce 2 double bonds to 1 in cis between 3-4
the enoyl-CoA isomerase can act
oxidation of fatty acids with odd number of carbons
propionyl - CoA (3 carbons) (not acetyl-CoA)
propionyl CoA –> succinyl CoA requires enzyme that uses coenzyme B12
steps in oxidation of fatty acids with odd number of carbons
addition of carboxyl to middle carbon, 2 unusual isomerizations and movement of methyl group that uses cobalt atom of B12
ketone bodies
produced when glucose precursors are not available to make glucose
ex: acetoacetate and hydroxybutyrate
sign of diabetic..
acetone on breath
acetoacetate unstable –> acetone, very volatile
thiolase
thiolase reaction in ketone body formation is reversal of same reaction in fatty acid metabolism (between oxidation and synthesis)
synthesis up to palmitate occurs in…
cytoplasm
fatty acids built using
acyl carrier proteins (ACP)
___ used to donate e’s in synthesis
NADPH
malonyl-ACP…
3 carbons
donated 2 Cs to growing fatty acid chain
CO2 lost in process
synthesis of fatty acids longer than ____ occur in___
longer than 16C occur in ER or mitochondria
in synthesis, a ___ intermediate is formed at ___
a D-hydroxyl intermediate is formed at C3
beta oxidation occurs in
mitochondrial matrix
beta oxidation uses ___
CoA
___ used to accept e’s in oxidation
NAD and FAD
beta oxidation yield
2 carbon acetyl - CoA units
oxidation of fatty acids longer than ___ occurs on ___
longer than 16 in peroxisome
in oxidation and __ intermediates is formed at ___
L-hydroxyl intermediate at C3
acetyl - CoA carboxylase
addition of carboxyl group to acetyl CoA –> malonyl coA (3C)
regulation of acetyl-CoA carboxylase
alloserically - inhibited by palmitoyl-CoA (first end product, feedback inhibition), activated by citrate
covalent modification - phosphorylation inhibits
CoA from malonyl-CoA swapped for …
swapped for ACP to start synthesis –> malonyl-ACP
acetyl-CoA gets into cytoplasm from mitochondria by….
citrate shuttle
acetyl-CoA linked to oxaloacetate in mitochondria –> citrate –>transported out –> citrate cleaved –> acetyl CoA + oxaloacetate in cytoplasm
only enzyme regulated in synthesis
acetyl CoA carboxylase
malonyl ACP is…
adding block for synthesis
acetyl ACP is …
starting block
decarboxylation of malonyl ACP –>
2 carbon addition to growing chain (onto carboxyl end)
1st reaction in saturated fatty acid synthesis
malonyl ACP + acetyl ACP
condensation - CO2 lost (CO2 on then off…)
saturated fatty acid synthesis ….
malonyl ACP + acetyl ACP
reduce - use NADPH –> alcohol
dehydration –> trans double bond
reduction - use NADPH –> 4C fatty acid (combine with new malonyl - ACP)
continues until 16 carbons (palmitoyl - CoA)
fatty acid synthase
multi enzyme complex
catalyzes all reaction up to 16 carbons
rotates through reactions like clock
desaturases
produce unsaturated fatty acids
in ER
use unusual e transferring initiated by donation of e from NADH to oxygen
essential fatty acids
must be in diet, cant make
in animals: linoleic and linolenic acids
cant make double bond past delta - 9
fatty acids longer than 16 produced by…
elongases - 2 carbons at a time
in ER and mitochondria
trans fatty acids produced by
partial hydrogenation of vegetable oil
prostaglandins
hormone like compounds made from arachidonic acid by prostaglandin synthase
prostaglandin synthase
many in body
reactions are forming cyclic oxygen containing compounds –> cyclooxygenases (COX)
prostaglandin effects
vasoconstriction/dilation uterine contractions aggregation/stickiness of platelets inflammation/pain maintenance of stomach lining
linoleic acid released from ___ by ___
released from glycerophospholipids by PLA2
PLA2 inhibited by
corticosteroids
treat sever inflammation/pain
linoleic acid—>
arachidonic acid
leukotrienes
from arachidonic acid via linear pathway
mucus production and bronchial constriction
cause asthma attacks and allergies
cyclic pathway from arachidonic acid
prostaglandins –> thromboxanes
thromboxanes
help make platelets sticky favoring aggregation
asprin and blood clotting
reduce synthesis of prostaglandins –> reduce thromboxanes –> reduce stickiness of platelets
prostaglandins get out of cell by
multi drug resistance protein
prostaglandins are a ___ hormone
local - only effects in location synthesized
