Hardman - Oxidation of Fatty Acids Flashcards

1
Q

Cystic Fibrosis

A

Pancreatic dysfunction

Growth failure, ADEK deficiency, bone disease

Not digesting fats

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2
Q

Need for Lipids

A
  • Building blocsk for phospholipids and glycolipids
  • Modification of proteins
  • Fuel
  • Hormones and intracellular messaging
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3
Q

3 Sources of Fatty Acids

A
  1. Diet
  2. Storage lipid droplets
  3. Fats synthesized in liver
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4
Q

Dietary Fats

A

90% TAGs

Multiple enzymes needed to digest each type

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5
Q

Stomach Fat Digestion Enzymes

A

Acid resistance lingual lipases

Gastric lipases

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6
Q

Enzyme which removes first two FA’s from TAGs?

Which does it remove?

A

Pancreatic Lipase removes FA at carbons 1 and 3

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7
Q

Colipase

How is it activated?

A

Anchors lipase at the lipase-aqueous interface

Cleavage by trypsin

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8
Q

Enzyme for digestion of cholesterol esters

A

Cholesterol esterase from pancreas

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9
Q

Enzymes for phospholipid (ex. phosphatidylcholine) digestion

Which carbons do these remove?

A
  1. Phospholipase A2 (#2 Carbon)
  2. Lysophospholipase (#1 Carbon)
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10
Q

How is lipid digestion hormonally controlled?

A

Cholecystokinin (CCK) - from jejunum and duodenum

(+) Gall Bladder - bile release

(+) Pancrease - enzyme release from exocrine cells

Secretin - produced in response to low pH of chyme (rich in bicarb)

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11
Q

What happens to fatty acids following intestinal lipase processing?

A

The TAGs which have been degraded to FAs / Glycerol are taken up by intestinal mucosa, and converted back into TAGs, and packaged on chylomicrons

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12
Q

What apolipoproteins label chylomicrons?

A

B-48

C-III

C-II

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13
Q

Chylomicron components

How do these components reach tissues?

A

TAGs incorporated with cholesterol, apolipoproteins (ApoC-II)

Move through lymphatic system and bloodstream to tissues

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14
Q

What enzyme converts chylomicrons to their components?

How is it activated?

A

Lipoprotein Lipase

Activated by apoC-II in capillary

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15
Q

What are fatty acids associated with when transported to other cells?

A

Albumin

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16
Q

Glycerol use during fat synthesis

A

Used by liver to produce glycerol-3-phosphate for:

glycolysis

gluconeogenesis

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17
Q

How are fatty acids transported into the cellular cytoplasm?

A
  1. Travel blood as TAGs (chylomicrons)
  2. Membrane bound lipases break down for transit
  3. Reform as TAGs in cytoplasm
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18
Q

MCAD

Medium Chain Acyl-CoA Dehydrogenase Deficiency

A

Symptoms: Lethargy, vomiting, appetite supression

Tests: Hypoketotic, hypoglycemia

19
Q

3 Stages for Mobilization of fatty acids as fuel

A
  1. Mobilization
  2. Activation and Transport to mitochondria
  3. Breaking down FA to acetyl-CoA
20
Q

What regulates mobilization of storage fatty acids?

Think: Under what conditions would you start to tap into your stored fatty acids?

A

Hormonally controlled lipase–activated by glucagon / epinephrine

Your glucose stores are low, and you need to produce energy if you’re burning your fat stores

21
Q

What is the fate of glycerol when all the FAs are cleaved off?

A

Enters glucose pathway, need to add phosphate first

Converted to Glycerol 3-Phosphate

22
Q

What is required for transport of FAs into mitochondria?

A

Activation w/ Acetyl-CoA (ATP dependent)

23
Q

What two major organ systems do not use Fatty Acids for fuel?

A

RBCs (no mitochondria)

Brain (blood brain barrier)

24
Q

What carriers activated fatty acids into mitochondria?

Hint: Hardman reaaaally emphasized this

A

Carnitine

25
Q

Do all fatty acids require carnitine?

A

No, short/medium (< 12 Carbons) can cross without carnitine

26
Q

What are sources for carnitine?

A
  1. Meat
  2. Synthesized from lysine and methionine by liver or kidney–not skeletal or heart muscle
27
Q

What is the membrane enzyme that is responsible for transfering acyl group from long chain fatty acid to carnitine?

What inhibits this?

Why?

A

Carnitine Acyltransferase I

aka Carnitine Palmitoyltransferase

aka CPT - I

(all same thing)

INHIBITED BY MALONYL CoA

Malonyl CoA is the first commited step of Fatty Acid Synthesis–can’t have breakdown/synthesis going on at the same time!

28
Q

Carnitine Deficiency (or CPT-1)

Source?

Results?

A

Source:

Liver Disease

Vegetarian Diet

Burns, Pregnancy

Hemodialysis (kidney disease)

Gentics

Results:

  1. Inability to synthesize glucose during a fast–low blood sugar, coma, death

2. Sustain exercise

29
Q

Steps for Fatty Acid B-Oxidation

A

Oxidation

Hydration

Oxidation

Thiolysis

  • Shortened by 2-carbons each cycle
30
Q

What are the electron acceptors in B-Oxidation?

A

FADH2, NADH

31
Q

What type of enzyme drive an oxidation rxn?

A

Dehydrogenase

32
Q

What are net products each OHOT round of B-Oxidation?

A

1 FADH2

1 NADH

1 Acetyl CoA

33
Q

How many cycles would a n-(even)-carbon require for complete oxidation?

A

(n/2) - 1

-1 because the last step cuts four carbons into two Acetyl CoA, so in reality the true “net” would be 2 Acetyl CoA for the last step

34
Q

Total ATP from complete B-Oxidation of Palmitate?

A

106 ATP

35
Q

If B-Oxidation handles even carbon fatty acids, what about Odd?

A

Final step (5-carbon) yields:

3-carbon Propionyl CoA and

2-carbon Acetyl CoA

  • Propionyl CoA converted to Succinyl CoA (5-carbon) to enter Citric Acid Cycle
36
Q

What coenzymes or vitamins are required for conversion of propionyl coa to succinyl coa?

A

Biotin (B7, Vitamin H)

B12

37
Q

What additional steps are required for unsaturated fatty acid processing in B-Oxidation?

A

Odd # Double Bonds: Isomerase

Even # Double Bonds: Reductase

iso** - **odd

r_e_d - _e_ven

38
Q

Refsum Disease

A

Genetic defect in peroxisomal enzyme responsible for initial step in oxidation of phytanic acid

Symptoms: Retinitis pigmetosa, progressive peripheral neuropathy, skeletal malformations, severe motor weakness

39
Q

a-Oxidation

(alpha-ox)

A

Takes place in peroxisomes

branched chain fatty acids

very long chain fatty acids

hydrogen peroxide byproduct

40
Q

Ketosis

3 major ketone bodies

A

Ketone bodies formed from acetyl CoA when fat degradation predominates

Ketone Bodies:

  1. Acetoacetate
  2. 3-hydroxybutyrate
  3. Acetone
41
Q

Conversion of 3-Hydroxybutyrate or Acetone from Acetoacetate depends on what?

A

NADH/NAD+ ratio,

High NADH = 3-hydroxy butyrate

High NAD+ = Acetone

42
Q

What will excess acetyl CoA eventually lead to?

A

High ketone production

43
Q

Diabetic Ketosis

A

Absence of insulin:

  1. Liver cannot provide ocaloacetate
  2. Insulin normally decreases fatty acid metabolism

– Liver will produce large amount of ketone bodies, lowering pH

44
Q
A