Download FA + GLYCEROL

FA + GLYCEROL
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GLYCEROL
o
Gluconeogenesis
o
FA synthesis
CARNITINE ACYLTRANSFERASE II – located in the
INNER MITOCHONDRIAL MEMBRANE
BETA OXIDATION
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FA -> Acetyl CoA
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4 steps:
FA
o
o
Oxidation
o
Storage
o
Free w/ albumin
OXIDATION (1ST)

Oxidation of FA by Acyl CoA
Dehydrogenase

Forms a double bond between
C2 & C3

Produces FADH2 from FAD
LIPOPROTEIN LIPASE – enzyme
FREE FATTY ACIDS – virtually all cells can use Fatty
Energy except Brain, RBC & Medulla
BETA OXIDATION
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Major pathway for catabolism of FA
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2 carbon fragments are cleaved producing
Acetyl CoA (enters Kreb’s Cycle)
o
HYDRATION

o
OXIDATION (2ND)
STEPS:

Hydroxyacyl CoA oxidized by
NAD+

Became 3-Ketoacyl CoA

Forms NADH
1. TRANSPORT OF FA INTO MITOCHONDRIA
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After FA are taken up by a cell, it is
converted to a CoA derivative (fatty
acylCoA)
o
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Fatty aclyCoA synthetase/thiokinase
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Transport to mitochondria
THIOLYTIC CLEAVAGE (THIOLYSIS)
*Mitochondrial membrane is impermeable

Cleavage of 3-Ketoacyl CoA by
thiol group of another CoA

Produces shorter Acyl CoA and
Acetyl CoA
CARNITINE SHUTTLE
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Acyl group must first be transferred Cytosolic
CoA to Carnitine
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Catalyzed by Carnitine Acyltransferase I
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Forming Fatty Acyl Carnitine I & II
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Inhibited by: MALONYL CoA
CARNITINE ACYLTRANSFERASE I – located in the
OUTER MITOCHONDRIAL MEMBRANE
Add H2O
ENERGY YIELD FROM BETA OXIDATION
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Each time an acetyl group (2 carbons) is
cleaved from acyl chain, it produces:
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1 NADH
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1 Acetyl CoA
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1 FADH2
Therefore:
*Carnitine is not needed inside the mitochondria
because it is only a shuttle
o
PALMITATE (16:0)
16/2 = 8 – 1 = 7cycles
* Fats yield high energy
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O.H.O.T. FORMULA = (n/2) – 1
PALMITATE – 7 CYCLES
o
7 NADH
x3ATP
= 21
7 FADH2
x2ATP
= 14
RELEASE OF FA FROM TAG
8Acetyl CoA x 12ATP = 96
131
Energy investment FAcyl CoA synthase _-2
Total ATP
129
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Mobilization of STORED FAT
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HORMONE – SENSITIVE LIPASE
o
Breaks stored fat
o
Present in ADIPOSE TISSUES
18 carbon = 8cycles
o
8 NADH
x3ATP
=
24
8 FADH2
x2ATP
=
16
TAG  FA + GLYCEROL
9 Acetyl CoA x12ATP = 108
HORMONE – SENSITIVE LIPASE
148 – 2 = 146
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OXIDATION OF ODD NUMBERED FA
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Same process until last 3 is reached
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PROPIONYL CoA instead of Acetyl CoA
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Propionyl CoA -> Methyl Malonyl CoA by
enzyme Propionyl CoA Carboxylase
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Methylmalonyl CoA -> Succinyl CoA by
enzyme Methylmalonyl CoA Mutase
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Activators:
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Epinephrine
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Low level glucose
Reactivators:
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Insulin
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High level glucose
FATE OF GLYCEROL
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Succinyl CoA – can enter Kreb’s Cycle
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Glycerol cannot be metabolized by adipocytes
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COMPUTATION:
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Lacks GLYCEROL KINASE transport to liver
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Phosphorylated or converted to DHAP
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Can participate in glycolysis/gluconeogenesis
o
17 carbons – 3= 14/2= 7-1 =
6cycles
6 NADH
x3ATP
= 18
6 FADH2
x2ATP
=
7 Acetyl CoA
x12ATP = 84
12
114
FA SYNTHESIS – can be created from Carbohydrates
& proteins
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Location: primarily in the LIVER; kidney,
lactating mammary glands, adipose tissues
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Required energy:
-2
112
Kreb’s Cycle (Succinyl CoA)
118
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o
+6
6 from Kreb’s cycle is constant for
ODD
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NADPH, Acetyl CoA, ATP
MAJOR SOURCES OF NADPH
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HMP shunt
o
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NADP dependent MALATE
HYDROGENASE

Byproduct: NADPH

Convert Malate to Pyruvate
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Occurs in cytosol: FA synthesis
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Acetyl CoA inside mitochondria
o
CITRATE SHUTTLE

OAA + Acetyl CoA to produce
CITRATE

Enzyme: ATP CITRATE LYASE –
removes citrate
2. CARBOXYLATION OF ACETYL CoA
TO MALONYL CoA
o
Outside the cytosol
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Acetyl CoA Carboxylase
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Requires ATP
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Coenzyme = BIOTIN
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Regulated step / IRREVERSIBLE
2 WAYS OF REGULATION OF ENZYME
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REDUCTION

DEHYDRATION
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REDUCTION
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Fatty acid synthase enzyme (7 activity)
2 domains
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TOTAL RESULT OF 7 STEPS –
production of 4 Carbon compound
STEPS:
1. PRODUCTION OF CYSTOLIC ACETYL
CoA

FURTHER ELONGATION AND DESATURATION OF
FA CHAINS
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Palmitate can be further elongated or
desaturated
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In humans, up to 9C double bonds
ESSENTIAL FA – have double bonds beyond C9
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LINOLEIC ACID 18:2 (9,12)
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LINOLENIC ACID 18:3 (9,12,15)
RELATIONSHIP OF GLUCOSE METABOLISM &
PAMITATE SYNTHESIS:
FA = Acetyl CoA + ATP + NADPH
1. Glycolysis produce pyruvate
2. OAA is produced by gluconeogenesis
SHORT TERM
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Undergoes activation by Citrate
3. Acetyl CoA – mitochondria
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Inactivated by Malonyl CoA
4. Citrate
5. Carbons of Cytosolic Acetyl CoA
LONG TERM
o
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Prolonged consumption of high carb or
fat free diets increases enzyme synth
(PRO)
High fat diet/fasting reduces FA synth
(ANTI)
3. FA SYNTHASE
Opposite of oxidation
o

CONDENSATION
STORAGE:
TAG= 3FA + GLYCEROL
FA  FATTY ACYL CoA
TAG (Storage Fat) = glycerol phosphate +
3Fattyacyl CoA
INSULIN – storage/anabolic
GLUCAGON – degradation/catabolic
- Rosette Go 100208 