Biochem Weight Loss Fa Metabolism 2

Front 1

FA storage

Back 1

Triglycerides
de novo synthesis in liver from glucose

Front 2

FA degradation (TG's)

Back 2

3FA's and one glycerol,

FA's go to liver ATP/NADH gluconeogenesis

to muscle spares glucose for glucose dependent tissues

Front 3

Describe degradation TG to FA in adipose and transport to appropriate tissues

Back 3

glucagon/epi activates HSL (hormone sensitive lipase, it's P'd)

TG-->3FA and glycerol(liver)

FA goes out of adipocyte to blood and is bound to albumin

goes to target tissue dissociates and binds to FABP

Front 4

What tissue can FA not go to?

Back 4

brain

Front 5

FA transport into mitochondria once it hits target tissues

Back 5

has to be activated by tagging an acetyl on it, and has to be transported via citrate (except SCFA and MCFA)

Front 6

where do SCFA and MCFA's get activated?

Back 6

in the mitochondrial matrix

Front 7

what activates FA's?

Back 7

Fatty acyl-CoA synthetase, uses two high E bonds, driven by pyrophosphatase,

families of synthetases are based on chain length

Front 8

Where does activation of LCFA and VLCFA's occur?

Back 8

mitochondrial intermembrane space (cytosol?)

Front 9

describe biochemically, the transport of activated FA into mito

Back 9

FA-SCOA --> FA-Carnitine

via CAT I

Front 10

what is CAT I inhibited by?

Back 10

malonyl-Coa

lots of malonyl-CoA means synthesis is happening in the cytosol, so dont want to transport newly made FA into mito for degradation

Front 11

CAT I

Back 11

rate limiting and regulated

Front 12

Deficiencies

Back 12

rare: CAT I II and translocase

CARNITINE DEFICIENCY
decreased syn (in premies)
defective membrane transporter in muscle heart kidneys

treatment: aviodance of fasting, low LCFA intake, supplement with MCTG and carnitine

Front 13

Beta oxidation of palmitic acid

Back 13

palmitic acid(16:0) + 7 FAD + 7 NAD --> 8 acetyl coa + 7 FADH2 + 7 NADH

Front 14

beta oxidation of stearic acid

Back 14

stearic(18:0) --> get 8 fadh2 8 nadh 9 acetylCoA

Front 15

steps of beta-oxidation

Back 15

FAD-deH (trans dbl bond between alpha and beta)

enoyl CoA Hydratase ( add water, get OH on beta C)

beta-hydroxyacyl CoA DeH-NAD
(double bond carboxy on beta C)

Beta-ketoacyl CoA thiolase ( cleave at beta C, add CoASH)

Front 16

which beta oxidation enzyme is chain-length specific

which transport enzyme is chain length specific

Back 16

acyl CoA DeH-FAD

fatty-acyl CoA synthetase (makes FA-SCoA)

Front 17

for LCFA beta-oxidation what enzymes are in a membrane bound complex?`

Back 17

enoyl CoA hydratase
beta-hydroxyacyl CoA DeH-NAD
Beta-ketoacyl CoA thiolase

(the last 3)

Front 18

what regulates beta oxidation (3)

Back 18

substrate concentration

malonyl Coa(inhibits CAT I)

AcetylCoA/ free CoA ratio (thiolase uses free CoA in the last step, so decreased free CoA means decreased beta ox)

Front 19

what does a high I/G ration do for FA synthesis? for beta-oxidation?

Back 19

high I/G increases synthesis and decreases oxidation
how??

Front 20

key regulated enzyme(s) of FA synthesis? or oxidation?

Back 20

synthesis: acetyl CoA carboxylase (makes malonyl coA, uses biotin PG)


oxidation: CAT I

Front 21

how many ATP per C do you get for beta oxidation of FA? how many from glucose?

Back 21

8atp/C for FA

6 atp/C for glucose

Front 22

Beta oxidation of odd-numbered FA's

Back 22

problem - 3C product eventually, left with propionyl CoA

add a C: CO2 ATP / Proprionyl CoA carboxylase biotin

change from D to L: methylmalonyl CoA racemase

change L-methylmalonyl CoA to succinyl CoA: methylmalonyl mutase Coenz B12

Front 23

what is the only glucogenic precursor from FA's?

Back 23

proprionate getting changed to succinyl CoA for the TCA cycle

Front 24

Beta-oxidation of unsaturated FA's

dbl bond at odd C

Back 24

problem: enoyl hydratase can't work on a cis kinked double bond

cleave normally till hit double bond

use enoyl isomerase to transform cis dbl bond at 3 to trans dbl bond at 2

Front 25

beta ox of unsaturated

dbl bond at even C

Back 25

beta oxidize till hit dbl bond at C4, and start initial deH of cycle 5 by making dbl bond (trans) at alpha-beta C

use nadph and dienoyl CoA reductase to make trans dbl bond at beta-c3

shift trans dbl bond at 3 to C2 using enoyl isomerase

this can then be used by enoyl CoA hydratase to finish cycle

Front 26

what is required for VLCFA oxidation?

Back 26

peroxisome - specific fatty acyl CoA synthetase

ABC transporter (into perox)

oxidase (direct reduction of O2)

Front 27

draw out VLCFA degradation

Back 27

VLCFA --> FA-SCoa (synthetase)

FA-SCoa --> enoyl-SCoa (FAD-oxidase)

Enoyl CoA -->BOH CoA(hydratase)

BOH --> beta Keto (DeH/get NADH)

Thiolase --> acetylCoA and eventually break down to MCFA

MCFA is transported out to mito via peroxisomal CAT (uses carnitine, generates CoA)

Front 28

Peroxisomal alpha oxidation of FA

Back 28

occurs at alpha b/c beta has a branch on it
shortens by 1C (CO2)

phytanic acid (20C) to pristanic acid (19)which can do beta oxidation

Front 29

how else can you ox branched FA?
minor pathway

Back 29

oxidation of methyl terminus (omega -ox)

Front 30

Synthesis of ketone bodies

Back 30

FA-> B-oxidation-> acetyl CoA

2AcetylCoA (2c) --> acetoacyl Coa(4c) + CoA
(thiolase)

acetoacyl Coa --> HMG coa (6c)+ CoA (HMG synthase)

HMG Coa --> acetoacetate + acetyl CoA (HMG lyase)

acetoacetate + NADH <-> BOH butyrate(BOH DeH)

acetone can be produced but its a dead end

Front 31

how many CoA's do you get? from KB synthesis

what do you use

Back 31

2 CoA

3 acetyl CoA's (regenerate 1)
1 NADH (interconversion from acetoacetate to BOH)

Front 32

Regulation of KB synthesis
2

Back 32

CoA supports B-oxidation
NADH from B-oxidation pushes acetoacetate to BOH

Front 33

Utilization of KB (not by liver!)

Back 33

IN MITO

BOH -> acetoacetate+NADH (BOH deH)

acetoacetate + Succinyl CoA --> acetoacyl CoA + Succinate (transferase)

acetoacyl Coa + Coa <-> 2 Acetyl Coa (thiolase)

Front 34

what is resting [KB]?

diabetic ketoacidosis[KB]?

Back 34

3-5 mM

up to 20 mM

Front 35

X-ALD

Back 35

xlinked
adrenoleukodystrophy
defect in ABC transporter for prox

can't get VLCFA's into perox

accumulate (esp in brain)

childhood form: develops normally till school age, then dementia, adrenal insufficiency

Front 36

Zellweger cerebrohepatorenal syndrome

Back 36

AR
VLCFA and phytanic acid accumulation
low survival
PEX Receptor found on the surface of peroxisomes recog's SKL on proteins

Front 37

Refsum disease

Back 37

AR
phytanic acid storage disease (alpha-ox)

defic in alpha-hydroxylase

restrict dietary phytanic acid

Front 38

MCAD

Back 38

medium chain acyl-CoA DeH

most common defect in B-oxidation

usually less than 2, can die

under 12C oxidation is greatly reduced,
Hypoketosis and hypoglycemia (more glucose use cause no KB, and little gluconeogenesis b/c ATP and NADH to drive gluconeo come from beta-ox

diagnosis: peal of carbons at c8

treatment: avoid fasting, carnitine supplementation, newborn screening