Metabolic functions of pantothenic acid in the human body, health effects

1. Metabolic functions of
pantothenic acid
Domina Petric, MD

2. General functions
Both CoA and ACP/4'-
phosphopantetheine function
metabolically as carriers of
acyl groups and activators of
carbonyl groups in a large
number of vital metabolic
transformations.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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3. Coenzyme A
Coenzyme A serves as an essential
cofactor for some 4% of known
enzymes, including at least 100 in
intermediary metabolism.
In these reactions CoA forms high-
energy thioester bonds with
carboxylic acids, the most
important of which is acetic acid.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. Coenzyme A
As acetyl CoA, the so-called
active acetate group can enter
the TCA cycle and be used for
the synthesis of fatty acids or
isopranoid compounds
(cholesterol, steroid hormones).
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Coenzyme A
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Coenzyme A
Acetyl CoA
is used in
the
oxidation
of amino
acids.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. Coenzyme A
• Acetyl CoA participates in the N-terminal
acetylation in more than half of eukaryotic
proteins.
This includes the processing of certain peptide
hormones from their polyprotein precursors:
• processing of ACTH to α-melanocyte-
stimulating hormone
• processing of ß-lipotropin to ß-endorphin
• tissue-dependent acetylation of those products
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. Coenzyme A
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. Coenzyme A
• Acyl CoAs are used to modify a large number
of proteins: GTP-binding proteins, protein
kinases, membrane receptors,
cytoskeletal proteins, mitochrondial
proteins, through the addition of long-chain
fatty acids.
• These reactions most frequently involve
palmitic acid, which is added post-
translationally in a reversible ester bond, and
myristic acid, which is added co-translationally
in an irreversible amide linkage.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Coenzyme A
Acyl CoAs are used to
activate fatty acids for
incorporation into
triglycerides, membrane
phospholipids and
regulatory sphingolipids.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. Coenzyme A
Acyl CoAs are
transacylated to
carnitine to form
energy-equivalent
acylcarnitines
capable of being
transported into the
mitochondria where
ß-oxidation occurs.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. Coenzyme A
Acyl CoAs are
involved in the
production of
acetoacetate, a
ketone body
derived from fat
metabolism when
glucose is
limiting.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Acyl-Carrier Protein (ACP)
• The acyl-carrier protein is a component of
the multienzyme complex fatty acid
synthase.
• In ACP, the cofactor functions to transfer
covalently bound intermediates between
different active sites with successive
cycles of condensations and reductions.
• 4'-phosphopantetheine is the prosthetic
group for the binding and transfer of the
acyl units during this metabolism.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. Acyl-Carrier Protein (ACP)
• The sulfhydryl group of the cofactor
serves as the point of temporary
covalent attachment of the growing
fatty acid via a thiol linkage each time a
malonic acid moiety is added by transfer
to the cofactor.
• The cofactor appears to function as a
swinging arm, allowing the growing fatty
acid to reach the various catalytic sites
of the enzyme.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14

15. Health effects
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15

16. Reduced serum cholesterol levels
• High doses (500-1200 mg/day) of
pantothine, the dimmer of
pantetheine, has been shown to
reduce serum total and low-density
lipoprotein-associated cholesterol
and triglycerides, and to increase
high-density lipoprotein-associated
cholesterol.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. Rheumatoid arthritis
• A randomized control trial
showed that high doses
(up to 2 g/day) of calcium
pantothenate reduced the
duration of morning stiffness,
the degree of disability and the
severity of pain for rheumatoid
arthritis patients.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17

18. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 17, 2018 18