L-Carnitine Flashcards

1
Q

Know Structure!!!

A

L- Carnitine [ZWITTERIONIC QUATERNARY AMINO ACID]

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2
Q

Where is 98% of the bodies L-Carnitine found?

A

Skeletal and heart muscle

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3
Q

What are the most significant dietary sources of L-Carnitine?

A

Red meat and dairy

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4
Q

If a vegetarian eats enough of these two amino acids, theoretically they should maintain a normal carnitine biosynthesis…

A

Lysine and Methionine [micronutrients as well]

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5
Q

Carnitine is absorbed in the intestine using what sodium dependent transport?

A

Organic cation transport number 2 [OCTN2]

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6
Q

Carnitine is absorbed in the intestine using what sodium dependent transport?

A

Organic cation transport number 2 [OCTN2]

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7
Q

What do the absorption rates vary between?

A

20-80%

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8
Q

From what amino acid can humans synthesize L-Carnitine?

A

L-Lysine [this is a dietary amino acid]

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9
Q

Synthesis of L-carnitie begins with the methylation of __________ by __________ to form trimethyllysine…

A
  • L-lysine

- S-adenosylmethionine (SAMe)

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10
Q

For L-Carnitine synthesis, what is an important cofactor that is necessary?

A

Vitamin C

[others - SAMe, Iron, B-6, Niacin]

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11
Q

The L-carnitine that is found in skeletal and heart muscles is transported there from which two organs?

A

Kidney and liver

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12
Q

Which enzyme is responsible for the transfer of L-Carnitine from the liver and kidneys –> skeletal and cardiac mm…..

A

y-butyrobetaine hydroxylase [this is the last enzymatic step in L-carnitine synthesis, only found in liver and kidney cells]

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13
Q

What sodium dependent transporter is L-carnitine transported into the skeletal muscle?

A

OCTN2 [against a considerable conc. gradient]

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14
Q

Elimination of L-carnitine occurs through which organ?

A

Kidney

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15
Q

Much like all AA, 95% of filtered L-Carnitine is reabsorbed by what structure? [hint: related to kidney]

A

Renal tubules

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16
Q

Nonvegetarians excrete 2x as much L-carnitine as compared to vegetarians… Why is this? [think back to which transporter moves Carnitine and also where Carnitine comes from in ppl’s diet…]

A

Vegetarians don’t consume meat, so their intake of L-carnitine directly is very low, they do however synthesize it via Lysine and Methionine, so it is made in their bodies. Nonvegetarians are meat eaters so they will be consuming enough Carnitine so it is not as integral to keep as much in the body because there is always more coming in. OCTN2 works very hard to keep L-carnintine in the body in vegetarians because these individuals need to keep as much of it in their bodies as possible as their diets do not support mass intakes of L-Carnitine! More efficient renal absorption in Vegetarians as well.

17
Q

What are the two biochemical functions of L-carnitine?

A
  1. Mitochondrial long-chain fatty acid transport [transporms free LCFA into Long-chain acylcarnitine for Beta-Ox]
  2. Modulation of Acetyl-Coenzyme A/Coenzyme A ratio [L-carnitine protects cells against toxic amts of Acetyl-CoA compounds, acts as a reservoir for acetyl residues]
18
Q

What are the three Carnitine transporters between the cytosol and the mitochondrial matrix?

A
  1. Carnitine palmitoyltransferase I (CPT I)
  2. Carnitine palmitoyltransferase II (CPT II)
  3. Carnitine acetyltransferase (CAT)
19
Q

Which CPT transporter is the rate-limiting step in transfer of long-chain fatty acids into the mitochondria?

A

CPT I

20
Q

*What is CPT I inhibited by during fatty acid synthesis?

A

Malonyl-CoA

21
Q

Has L-carnitine been successful for weight loss?

A

NO

22
Q

Supplementation of what over a 12 month period of time reduced mortality rates from 15% to 1.5% in patients who previously had a myocardial infarction.

A

L-Carnitine

23
Q

Supplementation of what mineral will decrease L-Carnitine synthesis…

A

Choline

24
Q

What type of medication can decrease L-carnitine plasma concentrations?

A

Anticonvulsant medications

25
Q

Which form of Carnitine is the only one to show biological activity?

A

L-Carnitine

26
Q

What happens when one supplements with D-Carnitine, specifically what will happen to L-Carnitine within the body?

A

D-Carnitine is a competitive inhibitor for L-Carnitine since it is not biologically active it will inhibit L-Carnitine absorption in the intestine.

27
Q

D-Carnitine causes issues, with L-Carnitine absorption, what is it’s effect on skeletal and cardiac mm.?

A

D-Carnitine will lead to a functionally relevant depletion of L-Carnitine in Skeletal and Cardiac muscle, BAD!

28
Q

Know fisher projection for D and L Carnitine…

A
  • L-Carnitine - the OH will be on the LEFT

- D-Carnitine - the OH will be on the RIGHT

29
Q

Supplementation with L-carnitine has shown to do what with heart function?

A
  • Replenish depleted myocardial carnitine levels
  • improve L ventricle function
  • NOTE: [27% reduction in mortality, 65% reduction in ventricular arrythmia]
30
Q

Accumulation of _______ can cause defects in _______ signaling which will then result in ________ resistance…

A
  • Fatty acids
  • Insulin
  • Insulin
31
Q

What facilitates the transport of fatty acids, and into what part of the cell for oxidation?

A
  • L-Carnitine

- MITOCHONDRIA

32
Q

By reducing lipid overload via the transport of fatty acids into the mitochondria for oxidation with L-Carnitine, what two things could this do overall for the body?

A
  • Reduce lipid overload

- Improve insulin sensitivity