Fat Mobilization and Degradation

Question 1

Concepts of FA Mobilization

Answer 1

After a meal, dietary lipid absorbed, transported, and stored at high efficiency but weak neg control (leads to obesity)

Even FA’s make acetyl CoA

Question 2

Main players

Answer 2

Liver for synth of FA and Carbs

Adipose for storage of FA

Users of FA = Muscle, heart, liver

Question 3

Transport of FA

Answer 3

FA’s carried in plasma by albumin (FFA is toxic, albumin is very soluble)

At tissue, FFA’s leave albumin and move transmemb via FABPs to cytosol

Question 4

Lipid mobilization from Adipose Cells

Answer 4

Glucagon and Epi activate adenyl cyclase (ATP to CAMP to PKA act)

PKA phosphorylates HSL and Perilipin. HSL clips FAs from TAG releasing 3 FAs and glycerol (goes to liver)

Question 5

FA Activation

Answer 5

In cytosol
FA act to Fatty Acyl CoA and AMP and 2 Pi’s

Intermediate = FA adenylated w/ AMP and CoASH

2 steps via FA-CoA synthetase (ATP)
1 step via pyrophosphatase (cleaves 2 Pi’s)

Energy rqr’d = 2 ATP

Question 6

FA Cytosol to Mito

Answer 6

FAcyl CoA and Carnitine to acyl carnitine and CoASH (OM; via CPT1)

FAcyl Carnitine to FAcyl-CoA (IM to matrix; via CPT2)

Question 7

Carnitine

Answer 7

Vit Bt
Inhib by Malonyl CoA

Synth in liver and muscle from Lysine and Methionine

Requires O2 and VitC

Question 8

SPCD

Answer 8

Systemic primary Carnitine Deficiency: AR, impaired FA ox … fasting state lethal

Question 9

Beta Ox of Even chain FA’s

Answer 9

Via Thiolytic cleavage at beta carbon to release Acetyl CoA

1. Oxidation releasing FADH2 and transenoyl
2. Hydration
3. Oxidation releasing NADH
4. Thiolytic cleavage making Acetyl CoA

Question 10

Energy yield of beta ox

Answer 10

For every FAD = 1.5 ATP; NADH = 2.5 ATP; Acetyl CoA = 10 ATP

Question 11

Beta ox of unsat FA’s

Answer 11

Needs isomerization to trans DBs
Odd = missing FAD
Even = missing NADH

Question 12

Odd Chain FA Beta Ox

Answer 12

Repeated beta ox to 3C (propionyl CoA)
Prop is enlarged to 4C via carboxylation (Via prop CoA carboxylase; ATP HCO3 and Biotin [vit A])

Converted to Succinyl CoA via B12 to gluconeogenesis (converted to malonyl CoA)

Question 13

Regulation of Beta Ox

Answer 13

No Direct Allosteric control
Inhib of CPT1 via malonyl CoA
Enhanced by lack of energy = blocks malonyl CoA synth and Acetyl CoA carboxylase is turned off (FA synth)

Question 14

VLCFAs

Answer 14

Peroxisomal Beta Ox, 1st step altered to H Peroxide (Not FADH2), rest is reg beta ox. Yields Acetyl CoA and NADH

Question 15

LC Branched FA

Answer 15

Alpha oxidation = alpha carbon hydroxylated and CO2 released yielding 3 Prop CoAs (to Succ CoA) and 3 Acetyl CoA

Question 16

omega Oxidation

Answer 16

Omega (term methyl group) carbon oxidized via ER located dehydrogenase (no feedback reg) via CYT p450, O2, and NADPH

Forms 2nd COOH - normal beta ox until it hits 6-10C which are H2O soluble. Goes to blood as MCFAs and excreted in urine as dicarboxylates

Function is to remove xenobiotics and toxic FA compounds

Question 17

Carnitine Def

Answer 17

Muscle - weakness, musc cramps, myoglobinuria

Hep - non ketotic hypoglycemia (prevents gluconeo)

Question 18

MCFA dehydrogenase Def

Answer 18

Most Common

1st oxidation is def leading to hypoglycemia and SIDS

Question 19

Refsum’s Disease

Answer 19

1st alpha ox w/ phytanate can’t occur leading to neurologic dysfx

Defect in phytenoyl CoA hydroxylase
Avoid greens and ruminant meats

Question 20

Methyl Malonic Acidemia

Answer 20

Vit B12 def/ MM-CoA mutase def

leads to metabolic acidosis = dev retard

Question 21

VLCFA oxidation def

Answer 21

Defect in peroxisome = Zellweger’s syndrome

Pt presents with increased plasma VLCFA affecting liver and brain