Fatty Acid Synthesis
Fatty Acid Synthesis
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FA + GLYCEROL o HYDRATION
Add H2O
GLYCEROL o OXIDATION (2ND)
o Gluconeogenesis Hydroxyacyl CoA oxidized by NAD+
o FA synthesis Became 3-Ketoacyl CoA
FA Forms NADH
o Oxidation o THIOLYTIC CLEAVAGE (THIOLYSIS)
o Storage Cleavage of 3-Ketoacyl CoA by thiol
o Free w/ albumin group of another CoA
Produces shorter Acyl CoA and Acetyl
LIPOPROTEIN LIPASE – enzyme
CoA
FREE FATTY ACIDS – virtually all cells can use Fatty Energy
ENERGY YIELD FROM BETA OXIDATION
except Brain, RBC & Medulla
BETA OXIDATION Each time an acetyl group (2 carbons) is cleaved from acyl
chain, it produces:
Major pathway for catabolism of FA o 1 NADH
2 carbon fragments are cleaved producing Acetyl CoA o 1 Acetyl CoA
(enters Kreb’s Cycle) o 1 FADH2
Therefore:
STEPS: o PALMITATE (16:0)
16/2 = 8 – 1 = 7cycles
1. TRANSPORT OF FA INTO MITOCHONDRIA
O.H.O.T. FORMULA = (n/2) – 1
After FA are taken up by a cell, it is converted to o PALMITATE – 7 CYCLES
a CoA derivative (fatty acylCoA)
7 NADH x3ATP = 21
Fatty aclyCoA synthetase/thiokinase
7 FADH2 x2ATP = 14
Transport to mitochondria 8Acetyl CoA x 12ATP = 96
131
*Mitochondrial membrane is impermeable
Energy investment FAcyl CoA synthase _-2
Total ATP 129
CARNITINE SHUTTLE
o 18 carbon = 8cycles
Acyl group must first be transferred Cytosolic CoA to 8 NADH x3ATP = 24
Carnitine 8 FADH2 x2ATP = 16
Catalyzed by Carnitine Acyltransferase I 9 Acetyl CoA x12ATP = 108
Forming Fatty Acyl Carnitine I & II 148 – 2 = 146
Inhibited by: MALONYL CoA
OXIDATION OF ODD NUMBERED FA
CARNITINE ACYLTRANSFERASE I – located in the OUTER Same process until last 3 is reached
MITOCHONDRIAL MEMBRANE PROPIONYL CoA instead of Acetyl CoA
Propionyl CoA -> Methyl Malonyl CoA by enzyme
*Carnitine is not needed inside the mitochondria because it is only a Propionyl CoA Carboxylase
shuttle Methylmalonyl CoA -> Succinyl CoA by enzyme
Methylmalonyl CoA Mutase
* Fats yield high energy Succinyl CoA – can enter Kreb’s Cycle
COMPUTATION:
CARNITINE ACYLTRANSFERASE II – located in the INNER
o 17 carbons – 3= 14/2= 7-1 = 6cycles
MITOCHONDRIAL MEMBRANE
6 NADH x3ATP = 18
BETA OXIDATION 6 FADH2 x2ATP = 12
7 Acetyl CoA x12ATP = 84
FA -> Acetyl CoA 114
4 steps: -2
o OXIDATION (1ST) 112
Oxidation of FA by Acyl CoA Kreb’s Cycle (Succinyl CoA) +6
Dehydrogenase 118
Forms a double bond between C2 & C3 6 from Kreb’s cycle is constant for ODD
Produces FADH2 from FAD
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RELEASE OF FA FROM TAG o High fat diet/fasting reduces FA synth (ANTI)
Mobilization of STORED FAT
HORMONE – SENSITIVE LIPASE 3. FA SYNTHASE
o Breaks stored fat o Opposite of oxidation
o Present in ADIPOSE TISSUES CONDENSATION
REDUCTION
TAG FA + GLYCEROL DEHYDRATION
REDUCTION
HORMONE – SENSITIVE LIPASE o Fatty acid synthase enzyme (7 activity) 2
Activators: domains
o Epinephrine o TOTAL RESULT OF 7 STEPS – production of 4
o Low level glucose Carbon compound
FURTHER ELONGATION AND DESATURATION OF FA
Reactivators:
CHAINS
o Insulin
Palmitate can be further elongated or desaturated
o High level glucose
In humans, up to 9C double bonds
FATE OF GLYCEROL
ESSENTIAL FA – have double bonds beyond C9
Glycerol cannot be metabolized by adipocytes
LINOLEIC ACID 18:2 (9,12)
Lacks GLYCEROL KINASE transport to liver
LINOLENIC ACID 18:3 (9,12,15)
Phosphorylated or converted to DHAP
Can participate in glycolysis/gluconeogenesis RELATIONSHIP OF GLUCOSE METABOLISM &
PAMITATE SYNTHESIS:
FA SYNTHESIS – can be created from Carbohydrates & proteins
Location: primarily in the LIVER; kidney, lactating
FA = Acetyl CoA + ATP + NADPH
mammary glands, adipose tissues
Required energy:
1. Glycolysis produce pyruvate
o NADPH, Acetyl CoA, ATP
2. OAA is produced by gluconeogenesis
MAJOR SOURCES OF NADPH 3. Acetyl CoA – mitochondria
o HMP shunt 4. Citrate
o NADP dependent MALATE HYDROGENASE 5. Carbons of Cytosolic Acetyl CoA
Byproduct: NADPH
Convert Malate to Pyruvate STORAGE:
STEPS:
1. PRODUCTION OF CYSTOLIC ACETYL CoA TAG= 3FA + GLYCEROL
o Occurs in cytosol: FA synthesis
o Acetyl CoA inside mitochondria
FA FATTY ACYL CoA
o CITRATE SHUTTLE
TAG (Storage Fat) = glycerol phosphate + 3Fattyacyl CoA
OAA + Acetyl CoA to produce CITRATE
Enzyme: ATP CITRATE LYASE –
INSULIN – storage/anabolic
removes citrate
GLUCAGON – degradation/catabolic
2. CARBOXYLATION OF ACETYL CoA TO
MALONYL CoA
o Outside the cytosol
o Acetyl CoA Carboxylase
o Requires ATP
o Coenzyme = BIOTIN
o Regulated step / IRREVERSIBLE