Heme synthesis - note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
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Erythropoietic protoporphyria

The porphyrias are inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway (also called porphyrin pathway). They are broadly classified as hepatic porphyrias or erythropoietic porphyrias, based on the site of the overproduction and mainly accumulation of the porphyrins (or their chemical precursors). more...

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Overview

In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, and cytochrome.

Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. This is, however, not the main problem; most enzymes—even when less functional—have enough residual activity to assist in heme biosynthesis. The largest problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine in which tissue they accumulate, whether they are photosensitive, and how the compound is excreted (in the urine or feces).

Subtypes

There are eight enzymes in the heme biosynthetic pathway: the first and the last three are in the mitochondria, while the other four are in the cytosol.

  1. δ-aminolevulinate (ALA) synthase
  2. δ-aminolevulinate (ALA) dehydratase
  3. hydroxymethylbilane (HMB) synthase
  4. uroporphyrinogen (URO) synthase
  5. uroporphyrinogen (URO) decarboxylase
  6. coproporphyrinogen (COPRO) oxidase
  7. protoporphyrinogen (PROTO) oxidase
  8. ferrochelastase

Hepatic porphyrias

The hepatic porphyrias include:

  • ALA dehydratase deficiency
  • acute intermittent porphyria (AIP): a deficiency in HMB synthase
  • hereditary coproporphyria (HCP): a deficiency in COPRO oxidase
  • variegate porphyria (VP): a deficiency in PROTO oxidase
  • porphyria cutanea tarda (PCT): a deficiency in URO decarboxylase

Erythropoietic porphyria

The erythropoietic porphyrias include:

  • X-linked sideroblastic anemia (XLSA): a deficiency in ALA synthase
  • congenital erythropoietic porphyria (CEP): a deficiency in URO synthase
  • erythropoietic protoporphyria (EPP): a deficiency in ferrochelatase

Porphyria variegata

Variegate porphyria (also porphyria variegata or mixed porphyria) results from a partial deficiency in PROTO oxidase, manifesting itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. It may first occur in the second decade of life; there is a cohort of sufferers living in South Africa descended from a single person from the Netherlands, Berrit Janisz, who emigrated in the 17th century.

Signs and symptoms

The hepatic porphyrias primarily affect the nervous system, resulting in abdominal pain, vomiting, acute neuropathy, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia. Cardiac arrhythmias and tachycardia (fast heart rate) may develop as the autonomic nervous system is affected. Pain can be severe and can, in some cases, be both acute and chronic in nature. Constipation is frequently present, as the nervous system of the gut is affected.

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The FAVORABLE Fats
From Prepared Foods, 6/1/00 by Elizabeth Mannie

Given fat's negative publicity, it may be difficult for many consumers to think of lipids as nutritional. This, however, is changing. Several speakers at Texas A&M University's short course discussed lipids that help fight disease and protect organs.

Nutritionists often recommend increasing intakes of fish and other sources of long-chain polyunsaturated fatty acids (PUFA) to improve health. The FDA is currently being supplied with data that supports a health claim linking omega-3 fatty acids with reduced risk of coronary heart disease (CHD). Long-chain omega-3 PUFA are important in fetal brain development, so much so that the EU recommends their inclusion in infant formulas.

"The mother's pool of PUFA is drained during pregnancy as she nourishes the fetus. In many cases she never completely recovers and is in a deficient state. This is believed to be a cause of postpartum depression [1]," stated Ian Newton, director of business development and regulatory affairs, Roche Vitamins Inc., in his presentation "Nutraceuticals from Marine Sources."

Other conditions with possible omega-3 PUFA involvement include arthritis, cancer, allergic asthma and depression. Most research, however, has focused on benefits to the brain and heart.

"Currently a nutritional gap of one gram per day exists between amounts of long-chain omega-3 PUFA recommended (l.25g/day) and amounts generally consumed in North America ([less than]0.25g/day), which is critical for infants, mothers and in the prevention of CHD," added Newton.

Oilseed By-products

Oilseeds contain medicinal compounds that affect many organs of the human body. Oil refining removes 32% to over 95% of these nutritional lipids that end up as by-products of the process. These byproducts include phosphatidylcholine, phosphatidylserine, phosphatidylinositol, [beta]-carotene, [beta]-sitosterol, [gamma]-oryzanol, [alpha]-tocopherol and [gamma]-tocotrienol, which are active ingredients in prescription and over-the-counter drugs as well as dietary supplements and functional foods.

Individual by-products play various roles in the human body such as providing necessary nutrients, lowering blood lipids and cholesterol, preventing liver damage, and decreasing cancer risks.

In the case of benign prostatic hyperplasia, [beta]-sitosterol improves symptoms and urinary flow parameters. Erythropoietic protoporphyria (EP), a genetic disorder, results in high concentrations of protoporphyrin in blood plasma. Symptoms include severe photosensitivity, which [beta]-carotene can reduce. Menopausal disorders and irritable bowel syndrome are improved by [gamma]-oryzanol.

Phosphatidylcholine, or lecithin, provides dietary choline (a B vitamin) for which the National Academy of Sciences has recently established a Dietary Reference Intake (DRI) of 550 mg/day for men and 425 mg/day for women [1]. The Food and Nutrition Board will be reviewing recommended dietary intakes for certain lipids during 2000, and researchers expect that RDAs for long-chain PUFA may be forthcoming.

Establishing recommended intakes for any single nutrient can be complex, as illustrated by vitamin E. Vitamin E ([alpha]-tocopherol) may decrease the rate of functional decline in Alzheimer's disease [2], reduce the risk of cardiovascular disease, and prevent/reverse hemolytic anemia in neonates.

"However, the optimum level of dietary vitamin E to support wellness is complicated because [alpha]-tocopherol is not the whole story," said Andreas Papas, Ph.D., Health and Nutrition at Eastman Chemical Company, Kingsport, Tennessee, during his presentation, "Tocopherols and Tocotrienols in Nutrition and Health." The other tocopherols and tocotrienols that comprise the vitamin E family of compounds support [alpha]-tocopherol's antioxidant activity and also have other unique functions for nutrition and health. Although their actions are not clearly understood yet, strong evidence points to their role in the prevention of some chronic diseases such as heart disease and some cancers, he added.

"Demand for oil refining by-products is on the rise. They are increasingly used in nutraceuticals and functional foods. However, they are generated at the expense of the nutritional quality of the oil," said R. D. (Bob) Reichert, Ph.D., Industrial Research Assistance Program, National Research Council of Canada, Ottawa, Ontario, in his presentation, "Vegetable Oil Processing, Medicine and Functional Foods?" "Whereas frying oils need rigorous refining to remove volatiles that create unpleasant working conditions in fast-food kitchens, salad oils probably do not need such rigorous refining," Reichert said.

References:

(1.) Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B 12, Pantothenic Acid, Biotin, and Choline, NAS, Washington USA (IN PRESS).

(2.) 1997. Practice guidelines for the treatment of patients with Alzheimers disease and other dementias of late life. Am. Psychictric Assoc. Practice Guidelines, 39p supplement Am. J. Psychiatry 154, 5.

Now In a Store Near You

Within the past 12 months, Nestl[acute{e}] rolled out an Omega Plus cream cheese, yogurt and milk in Brazil. In Malaysia, it promoted its canned powdered milk as a "high calcium reduced-fat milk powder with omega 3 and 6 'heart healthy' fatty acids."

"We are increasing our efforts to gather information on ingredient statements and nutritional content of new products," says Lynn Domblaser, editor, New Product News, Mintel International. A database search for specific fatty acids using the words "linoleic," "CLA," "linolenic," and "omega" produced a list of 96 individual newly introduced products or product lines from around the world in the last year. Some 23 food and supplement products or lines contained linoleic and/or linolenic in their ingredient and/or nutritional statements. As an essential fatty acid, linoleic is needed for basic nutritional purposes and can be added as an ingredient. However, these compounds are also intrinsically present in plant materials and most often incorporated that way. For example, Finland's Camelia introduced a cold-pressed sativa oil high in these components. Health From The Sun (USA) boasts its vegetarian oil capsule line of flax, borage, pumpkin seed or wheat germ oil as sources of EFAs.

The presence of omega-3 fatty acid was promoted in 68 products or product lines around the world. This higher incidence partially reflects the greater likelihood for Mintel to pick up terms promoted on front labels, says Domblaser. "Omega" is more front label worthy than "linolenic." Dietary supplements and health bars, dairy and egg products, cereals and bakery products all extolled their omega content. In Norway. Moller dietary supplements claimed endorsement by LHL, Norway's national society for those with heart and lung diseases. Spain's Carnicas Serrano introduced omega-fortified turkey-based products and ham. And, last summer in the U.S., Pilgrim's Pride went into test market with omega-3 and -6 fortified chicken breast.

Claudia O'Donnell

COPYRIGHT 2000 Cahners Publishing Company
COPYRIGHT 2000 Gale Group

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