Fatty Acids Flashcards

Question

Cholesteryl ester

Answer 1

Cholesterol -OH group esterified to the carboxyl group of an fFA

Answer 2

1. Chylomicron is released into the lymphatic system, then bloodstream to reach tissues 2. In the capillaries, **ApoC-II** (a chylomicron apolipoprotein) activates lipoprotein lipase 3. **Lipoprotein lipase** converts chylomicron TGs to free FAs and glycerol 4. **Free FAs** enter peripheral cells and are converted back to TGs for 1. storage in adipocytes or 2. oxidized for fuel in muscle cells.

Answer 3

Increase of lipids (esp vitamins & essential FAs) in the feces Caused by disturbance of lipid digestion and/or absorption --\> deficiencies _{Tx: Increase short- and medium FAs in the diet because they don't require incorporation into micelles to be taken up by intestinal mucosa}

Answer 4

in the intestine, the liver, and adipose cells.

Answer 5

1. **Glycerol 3-phosphate** produced from 1. DHAP reduction (in liver and adipose) or 2. Glycerol phosphorylation (in liver) 2. **FA chain is activated by CoA** 3. **Acyl transferase** attaches FA to carbon-1 of glycerol-3-phosphate, then again to carbon-2 --\> **phosphatidic acid** 1. ****This can also be a substrate for phospholipid synthesis. 4. **Phosphatidic acid phosphatase** removes the phosphate at carbon-3 --\> **1,2-Diacylglycerol (DAG)** 5. **Acyl transferase** attaches FA to carbon-3 of DAG --\> TG

Answer 6

* It has both * **G3P dehydrogenase** to turn DHAP (well-fed) to G3P * **Glycerol kinase** to turn Glycerol (fasting) into G3P In contrast, adipose cells only have G3P dehydrogenase

Answer 7

**Glycerol goes to the liver for phosphorylation** **Free FAs** leave to be used by other cell types. _{This set up prevents the reverse reaction (fFAs turning back into TGs) from happening in the adipocyte.}

Answer 8

1. **Glucagon/epinephrine** signal through GPCRs to elicit a cAMP-dependent 2nd msger cascade to PKA 2. **PKA** phosphorylates and activates **hormone-sensitive lipase** and **perilipin** 1. ****Perilipin coats fat droplets; unphosphorylated, it prevents lipase from penetrating 3. Lipase penetrates and **hydrolyzes TGs** into glycerol and free FAs 4. **Free FAs** enter the blood and ride on serum **albumin** to enter other cell types 5. In **muscle cells**, they are oxidized as fuel

Answer 9

* **Free FAs**: * Half used by peripheral tissue for E * Half go to the liver to be repackaged into new TGs that are * **exported to the peripheral cells (fasting)** * **stored back in adipocytes (well-fed)** * **Glycerol**: Go to the liver may be used for * **gluconeogenesis** (**fasting**) * **turned into G3P for TG synthesis (well-fed)**

Answer 10

Insulin (well-fed) * stimulates synthesis and secretion of **lipoprotein lipase** by adipocytes to **hydrolyze TGs in circulating apolipoprotein complexes** * The liver uses the fFAs to make new TGs, which are exported for other peripheral cells. * The adipocytes use the fFAs to make new TGs in fat droplets * Inhibits hydrolysis of TGs

Answer 11

**Well-fed:** Muscle cells want to use glucose - not TGs- so they **don't express lipoprotein lipase.** **Fasting:** glucose needs to be reserved for the brain, so muscle cells **express** **lipoprotein lipase** as a mechanism to **gain an alternate fuel source - fFAs.** **Cardiac muscle** *always* secretes lipoprotein lipase bc they get most of their E from FA metabolism.

Answer 12

Mitochondrial matrix 1 **NADH**, 1 **FADH₂**, and 1 **Acetyl CoA** (can be oxidized or turned to ketobone bodies)

Answer 13

1. Mobilized **FAs** from adipocytes enter the **cytosol** 2. **Fatty acyl CoA synthetase** activates it w/ CoA 3. Transport into the **mitochondria** for **B-oxidation**

Answer 14

**Carnitine acyl transferase I (CAT I)** in the OMM **Carnitine acyl tranferase II (CAT II)** on the IMM Move **CoA** from cytosol into the mitochondrial matrix CAT I turns FA-CoA to FA-Carnitine, which passes thru the OMM AND IMM into the matrix. CAT II in the matrix turns it back to FA-CoA, releasing free carnitine to shuttle back out to the cytosol.

Answer 15

* **Primary carnitine deficiency**: * Autosomal recessive * CAT I or CAT II malfunctions or Improper renal absorption of carnitine/carnitine trasnport * --\> **Liver** can't utilize LCFAs for fuel * **Encephalopathy, hypoglycemia, coma, death in infancy/childhood** * **Secondary carnitine deficiency** caused by * **liver disease** (inadequate carnitine) * **malnutrition** * **increased carnitine requirements** (pregnancy, burns, trauma) * **hemodialysis**

Answer 16

high carb, low LCFA diets Carnitine & MCFA supplements Monitor glucose to avoid hypoketotic hypoglycemic encephalopathies

Answer 17

1. Oxidation by **acyl-CoA dehydrogenase** --\> FADH2 2. Hydration by **enoyl-CoA hydratase** 3. Oxidation by **B-hydroxyacyl CoA dehydrogenase** --\> NADH 4. **Cleavage** by **acyl-CoA acetyltransferase** Shortens the chain by 2 carbons All rxns occur between a- and B-carbons.

Answer 18

* AR * Deficiency in the **acyl-CoA dehydrogenase** for medium-length acyl chain _{(6-10 carbons)} * --\> Accumulation of **octanoic acid** **in blood**; hypoglycemia; muscle weakness; sleepiness; vomiting; coma * High **6-10C mono- and dicarboxylic acids in urine** * Sudden infant death syndrome (**SIDS**) * Tx (children can live healthy lives): * Low fat, high carb diet * Avoid fasting

Answer 19

For **MCFA oxidation** Occurs in the **ER of liver and kidney cells** Carboxylic acid is produced at the w-end, making the FA a **dicarboxylic acid** that can undergo B-oxidation in the mitochondria

Answer 20

MCADD prevents normal B-oxidation --\> w-FA oxidation is upregulated, producing dicarboxylic acdis

Answer 21

Produces **proprionyl CoA**, which can be converted to **succinyl CoA** (a CAC intermediate)

Answer 22

**Biotin** adds CO₂ to produce methylmalonyl-CoA **Vitamin B₁₂** is required for a mutase to convert L-methylmalonyl-CoA to succinyl-CoA

Answer 23

problem with the mutase that turns L-methylmalonyl-CoA to succinyl-CoA --\> can't oxidize odd-chain length FAs, branched amino acid chains, or replenish key CAC intermediates.

Answer 24

* Occurs in the **peroxisome** * Transport into peroxisome **doesn't require carnitine** * In the initial oxidation reaction to produce the delta² trans-enoyl-CoA and FADH₂, the **FADH₂ is oxidized back to FAD** and **O₂ is reduced to H₂O₂** * _{Eventually VLCFAs are oxidized to MCFAs and SCFAs --> they leave peroxisome with acetylCoA as carnitine derivatives and enter the mtiochondria}

Answer 25

* **Zellweger syndrome**: inability to target peroxisomal matrix proteins to the peroxisome * **X-linked adrenoleukodystrophy**: inability to transport VLCFAs across peroxisomal membrane

Answer 26

* Occurs in the peroxisome * ***a-*****hydroxylase** introduces an -OH on *a*-carbon and removes the carboxyl group * The old *a*-carbon is now the new carboxyl-carbonn --\> normal B-oxidation yields 3C **propionyl-CoA,** instead of acetylCoA

Answer 27

* Genetic defect in **Phytanoyl-CoA hydroxylase** (the a-hydroxylase involved in the a-oxidation of Phytanic acid) * --\> high levels of **Phytanic acid** in blood & tissues * Severe **neurological problems**: chronic polyneuropathy, cerebellar dysfunction, blindness, deafness * Tx: **don't eat foods w/ phytanic acid**

Answer 28

Synthesis: **condensation \> reduction \> dehydration \> reduction**

Answer 29

**malonyl CoA**, a 3 carbon molecule. During condensation, CO2 is removed and the remaining acetyl group is donated.

Answer 30

**Acetyl-CoA carboxylase** * **Biotin carrier protein** swings between two domains * In the biotin _carboxylase domain,_ **biotin becomes carboxylated & activated with CO2** --\> swivel to.. * In the _transcarboxylase domain_, the **CO2 is donated to acetyl-CoA** to form **malonyl CoA**

Answer 31

* *Wellfed*: **A****cetyl-CoA carboxylase (ACC)**is**unphosphorylated & active** * ****Acetyl-CoA --\> malonyl CoA for FA synthesis * Also inhibits CAT I to prevent B oxidation * *Fasting:* **ACC is phosphorylated & inactive**, malonyl CoA is low --\> B oxidation prevails

Answer 32

* Insulin activates a phosphatase that maintains ACC in unphosphorylated & active state * Glucose \> pyruvate \> acetyl CoA \> \*malonyl CoA\* * --\> malonyl CoA inhibits CAT1 and is used for FA synthesis

Answer 33

insulin & citrate _{remember how citrate part of how mitochondrial AcetylCoA is transported into the cytosol}

Answer 34

* Glucagon stimulates **PKA to phosphorylate ACC** into its inactive form * --\> stimulates B oxidation since CAT I are free * LCFA also inhibits ACC --\> B oxidation of LCFAs

Answer 35

During fasting, **free FA can be broken down in the liver into acetyl-CoA** and ultimately to **ketone bodies** that enter the bloodstream and can be **used by other tissues (muscle)** for energy, thus saving the glucose for the brain (though it can also use KBs)

Answer 36

acetoacetate & B-hydroxybutyrate Converted back to acetyl CoA in muscle tissue and oxidized for energy.

Answer 37

In a T1D, circulating glucose isn't taken up by cells --\> fFAs are oxidized and KBs are produced. **Acetoacetate can spontaneously decarboxylate into acetone** --\> acetone breath, ketonemia, keonuria, and diabetic ketoacidosis

Answer 38

**FA**: long hydrocarbon tail w/ terminal carboxylic acid at one end **TGs**: glycerol back bone with 3 esterified FA chains **Sphingolipids & glycolipids**: sphingosine backbone with an amide-linked FA + phosphate + polar group (glycolipid doesn' thave the phosphate **Cholesterol**: 4-ring steroid structure, with a hydrophilic OH group and an acyl tail at the other

Answer 39

_{TG synthesis: 2 FAs are activated by acyl-CoA synthetase, and then esterified by acyl transferase at C1 & C2 to glycerol-3-phosphate --> phosphatidic acid. The phosphate group is removed and a third FA is activate dand esterified at C3.} ## Footnote **Phospholipids: Instead of removing the phosphate group of phosphatidic acid, a polar head group is added**

Fatty Acids Flashcards

(64 cards)