CHAPTER 41: NIACIN (B3) AND PANTOTHENIC ACID (B5)

OBJECTIVES

  1. Contrast the different types of dehydrogenase reactions using NAD+ as a coenzyme, to those using NADP+ as a coenzyme.

Dehydrogenase reactions using NAD+ as a coenzyme are typically involved in catabolic pathways, while those using NADP+ as a coenzyme are typically involved in anabolic pathways

  1. Trace biochemical steps in the conversion of dietary nicotinamide and/or nicotinate to NAD+ .

Dietary nicotinamide and/or nicotinate are converted to NAD+ by the Preiss-Handler pathway through a series of biochemical reactions that involve the enzymes nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthase.

  1. Explain how dietary pyridoxine (B6), Leu and/or Trp can affect physiologic supplies of NMN, and thus NAD+ .

Dietary pyridoxine (B6), Leu and/or Trp can affect physiologic supplies of NMN, and thus NAD+, by altering the activity of enzymes involved in the Preiss-Handler pathway

  1. Recognize what is meant by a "niacin equivalent."

A niacin equivalent is a measure of the amount of niacin in food that can be converted to niacin in the body.

  1. Explain the causes and symptoms of Hartnup syndrome and pellagra.

Hartnup syndrome is a hereditary metabolic disorder that makes it difficult for your body to absorb certain amino acids from your intestine and reabsorb them from your kidneys and excessive amounts of amino acids in their urine. Skin rash and a lack of coordination of voluntary muscle movements, known as ataxia. These are the signs and symptoms characteristic of Hartnup disease, which typically affects the skin and brain. Symptoms normally start to appear in infancy or the first few years of life.

Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). It can also be caused by not getting enough tryptophan in your diet. Tryptophan is an amino acid that helps your body make niacin. Pellagra can cause dermatitis, diarrhea, and dementia. A skin rash called “pellagra” is a common symptom. It usually results from exposure to sunlight. It’s an intermittent red and scaly rash that typically appears over your face, neck, hands, and legs. It’s initially red, but over time it can progress to an eczematous-like rash. With prolonged sun exposure, the changes in your skin pigmentation can become permanent.

  1. Identify the coenzyme forms of pantothenate.

The coenzyme forms of pantothenate are CoA and acyl carrier protein.

  1. Describe reactions in the TCA cycle that are dependent upon a coenzyme form of pantothenate.

The TCA cycle is dependent upon CoA for the formation of acetyl-CoA from pyruvate and for the formation of succinyl-CoA from α-ketoglutarate.

  1. Show how vitamin B5 participates in both fatty acid β-oxidation and fatty acid biosynthesis (see Chapters 55 & 56).

Vitamin B5 participates in fatty acid β-oxidation by forming acyl-CoA from fatty acids. Vitamin B5 also participates in fatty acid biosynthesis by forming malonyl-CoA from acetyl-CoA.

  1. Indicate how CoA.SH assists in the incorporation of a volatile fatty acid (propionate) into hepatic gluconeogenesis (see Chapter 37).

CoA.SH (Coenzyme A) is a molecule that plays a crucial role in the metabolism of fatty acids. It is involved in the process of beta-oxidation of fatty acids, which occurs in the mitochondria of cells. During beta-oxidation, fatty acids are broken down into acetyl-CoA molecules, which can be used for energy production.

Propionate is a volatile fatty acid that can be incorporated into hepatic gluconeogenesis via succinyl-CoA. Succinyl-CoA is converted to oxaloacetate by the enzyme succinyl-CoA:3-ketoacid CoA transferase (SCOT). OAA can then be used in the gluconeogenic pathway.

  1. Identify vitamin B5-dependent reactions catalyzed by -ALA synthase, HMG-CoA reductase and HMG-CoA lyase (see Chapters 32, 61 & 71).

 ALA synthase is an enzyme that catalyzes the first step in the biosynthesis of heme. It is a vitamin B6-dependent enzyme.

HMG-CoA reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, which is the rate-limiting step in cholesterol biosynthesis. It is a vitamin B5-dependent enzyme.

HMG-CoA lyase is an enzyme that catalyzes the cleavage of HMG-CoA into acetyl-CoA and acetoacetate. It is a vitamin B5-dependent enzyme.

  1. Identify two decarboxylation reactions of the TCA cycle that require lipoic acid.

Two decarboxylation reactions of the TCA cycle that require lipoic acid are the conversion of pyruvate to acetyl-CoA and the conversion of alpha-ketoglutarate to succinyl-CoA. Lipoic acid is a cofactor for 2 enzymes in the TCA cycle: pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.