Structure and function of heme
In general, haem iron from foods of animal origin meat, poultry and fish is well absorbed, but the non-haem iron in vegetable products, including cereals such as wheat, maize and rice, is poorly absorbed. In many areas where goitre is endemic the majority of people have some evidence of thyroid enlargement. Annals of Internal Medicine. Increasing evidence suggests that iron deficiency as manifested by low body iron stores, even in the absence of overt anaemia, is associated with poorer learning and decreased cognitive development. Monitoring the number of platelets in blood platelet count during cardiac surgery also helps the healthcare practitioners maintain a delicate balance between bleeding and clotting. The prime symptom of emphysema, which is always accompanied by a loss of elasticity of the lung, is shortness of breath, initially on exercise only, and associated with loss of normal ventilatory ability and increased obstruction to expiratory airflow.
Addition of the sulfhydryl groups of cysteine side chains across these vinyl groups can produce covalent bonds between heme and some of its apoproteins. Such covalent attachment occurs for example in cytochrome C oxidase, but it does not happen in hemoglobin. Hereditary deficiencies are known for each of the enzymes in the synthetic pathway. Clinical symptoms are due to both lack of heme and to the accumulation of biosynthetic intermediates.
A lack of heme therefore disinhibits this enzyme and amplifies the accumulation of intermediates upstream of the enzyme defect in question. Backed-up synthetic intermediates often undergo spontaneous conversion to aberrant products. Inhibition of heme synthesis can also result from causes other than enzyme defects. The most common cause is iron depletion; another one is deficiency of vitamin B 6 , which can result from malnutrition or, in inflammatory intestinal diseases, from malabsorption.
Vitamin B 6 pyridoxin is the precursor of pyridoxal phosphate, the coenzyme in aminolevulinate synthase. Lead intoxication causes inhibition of porphobilinogen synthase see slide Regardless of the underlying cause, the inhibition of heme synthesis will result in red blood cells that are smaller and contain less hemoglobin than normal ones.
This condition is named microcytic, hypochromic anemia. The accumulation of porphyrin precursors in various enzyme defects in porphyrin synthesis can cause photosensitization of the skin. The clinical picture can vary a bit, depending on the specific intermediate. As an example, we will consider the disease porphyria cutanea tarda translated: Here, the deficient enzyme is uroporphyrinogen III decarboxylase see slide The accumulating uroporphyrinogen distributes throughout the body and becomes oxidized non-enzymatically to the non-physiological product uroporphyrin III.
In the skin, uroporphyrin III can absorb photons and then react with molecular oxygen to produce reactive oxygen species; the latter inflict the skin tissue damage that is illustrated in the slide.
An important aspect of treatment is the protection of skin from direct sunlight. The absorbed wavelength range or absorption spectrum differs between the various porphyrins. Uroporphyrin III has an absorption peak at nm, which is at the blue end of the visible spectrum; this peak is readily detectable in blood serum samples left. The sun light is more intense in the visible range than in the UV range. Sun screen lotion, which is designed to absorb UV light but not visible light, will not prevent photosensitization by uroporphyrin III.
Sporadic PCT is often associated with disturbances of iron homeostasis. In homozygous form, this gene defect causes hemochromatosis , a disease that is characterized by severe iron overload. HFE knockout mice show increased intestinal expression and activity of iron uptake transporters. Iron overload of the liver can also occur in chronic infections and in other chronic inflammatory diseases see section Blood letting—which depletes iron—is reportedly beneficial in PCT, regardless of the cause of the iron overload.
The genetic defect in acute intermittent porphyria concerns the enzyme porphobilinogen deaminase. Porphobilinogen is excreted with the urine and, through spontaneous oxidation, forms a characteristic red pigment. The dysregulation mainly affects heme synthesis in the liver. As the name of the disease suggests, it is not always manifest but only intermittently.
Heme is the prosthetic group of cytochrome P enzymes, which are important in drug metabolism and are induced in the liver by various drugs see slide It appears that ALA synthase is induced along with the cytochrome P enzymes, and AIP attacks are often triggered or aggravated by the application of such drugs. Specific drugs that induce cytochrome P and ALA synthase include barbituric acid derivatives and carbamazepine, which were, and occasionally still are, used in the treatment of psychiatric symptoms.
Fatal outcomes have occurred when AIP patients were misdiagnosed and treated with barbituric acid derivatives. Red blood cells have a regular lifespan of days although it can be considerably shorter in some diseases. At the end of this lifespan, they are captured and ingested by phagocytes in the spleen and the liver.
When the globin protein is proteolytically degraded, heme is released. Heme itself undergoes degradation mostly in the liver. Ring cleavage by heme oxygenase produces biliverdin, which is in turn reduced to bilirubin. Some bilirubin is excreted into the bile as such; however, the greater share is first conjugated with glucuronic acid by UDP-glucuronosyltransferase, form 1A1, and excreted thereafter. The major transport protein responsible for excretion of the diglucuronide is an ABC transporter ABCC2 , the same one that also secretes bile acids see slide In the anaerobic environment that prevails inside the colon, the released bilirubin subsequently undergoes reduction, again by bacterial enzymes, to variously colored pigments that produce the stool color.
Another reduction product, urobilinogen, is taken up and excreted with the urine, causing the yellow color of the latter. Some fairly simple clues can narrow down the cause of jaundice in a given patient. If excretion of bilirubin is blocked, the pigments derived from it will be absent, and the stool will have a grayish color.
Hemolysis consists in the accelerated decay of red blood cells; it may result from biochemical causes such as glucosephosphate dehydrogenase deficiency see section 9. In hemolysis, the serum level of unconjugated bilirubin will be more strongly increased than that of the diglucuronide.
On the other hand, when the flow of the bile is backed up, the conjugated bilirubin will spill back into the serum and will be increased. Liver diseases can affect synthesis, conjugation and biliary secretion of bilirubin in various degrees, and either form of bilirubin can be more strongly increased than the other.
Neonatal jaundice is a normal event that is caused by a transiently low level of UDP-glucuronosyltransferase 1A1. If the serum level of bilirubin gets too high, however, it may accumulate in the brain and cause neurological problems see next slide. To prevent this, newborns can be treated with phototherapy see slide As in many other gene defects, there are variants with total or partial disruption of enzyme activity. When residual enzyme activity is present, it is possible to increase it with drugs such as phenobarbital that transcriptionally induce it.
As in neonatal jaundice, phototherapy is also used in Crigler-Najjar syndrome, but its efficiency decreases with time, since the growth of the body reduces its surface to volume ratio, and therefore a diminishing fraction of the bilirubin in the body can be reached by illumination. The disease is best treated with liver transplants, as the transplanted liver will not be affected by the underlying gene defect and be able to conjugate and excrete bilirubin. This slide shows a brain section from a patient with severe bilirubin encephalopathy.
The yellow color in the deeper structures of the forebrain, the so-called basal ganglia , is due to bilirubin accumulation. Through an unknown biochemical mechanism, bilirubin causes damage to the basal ganglia, which results in motor dysfunction and other neurological symptoms. In phototherapy, bilirubin absorbs photons and subsequently undergoes cis-trans isomerization across the two remaining double bonds between the pyrrole rings of the bilirubin molecule, as well as ring formation [ ].
This slide shows some of the photochemical reaction products. The 4Z,15Z isomer of bilirubin top left is the one that is produced directly by biliverdin reductase, and which is eliminated very slowly in the unconjugated form.
The other isomers are eliminated more rapidly; the fastest rate of elimination is observed with lumirubin cyclobilirubin. While the absorption maximum of bilirubin is in the blue wavelength band, green light reportedly produces lumirubin more efficiently, and it also induces less cytotoxic byproducts in cell culture models [ ]. It seems, however, that blue lamps are still more widely used in practice, and the literature does not make mention of significant side effects of blue light, even in the long-term treatment of Crigler-Najjar patients [ ].
The inhibition of heme oxygenase with Sn-mesoporphyrin has been used successfully in clinical studies to treat neonatal jaundice. The study summarized in this slide examined the effectiveness of Sn-mesoporphyrin in the treatment of newborns with glucosephosphate dehydrogenase deficiency see slide 9.
In this condition, the lifespan of red blood cells is diminished, which increases the rate of heme degradation; newborns therefore are at an increased risk of severe jaundice.
Remarkably, a single injection of the drug was sufficient to reduce the peak levels of bilirubin to a greater extent than the reference treatment phototherapy. Phototherapy currently remains the standard treatment in clinical practice. Figure prepared from original data in [ ]. Nitric oxide is an important signaling molecule.
Conditions such as depression, dementia , schizophrenia , anorexia nervosa , and bulimia can lead to malnutrition. Some people cannot leave the house to buy food or find it physically difficult to prepare meals. Those who live alone and are isolated are more at risk. Some people do not have enough money to spend on food, and others have limited cooking skills. If the body does not absorb nutrients efficiently, even a healthful diet may not prevent malnutrition. People with Crohn's disease or ulcerative colitis may need to have part of the small intestine removed to enable them to absorb nutrients.
Celiac disease is a genetic disorder that involves a gluten intolerance. It may result in damage to the lining of the intestines and poor food absorption. Addiction to alcohol can lead to gastritis or damage to the pancreas. These can make it hard to digest food, absorb certain vitamins, and produce hormones that regulate metabolism. Alcohol contains calories , so the person may not feel hungry. They may not eat enough proper food to supply the body with essential nutrients.
Not breastfeeding, especially in the developing world, can lead to malnutrition in infants and children. In some parts of the world, widespread and long-term malnutrition can result from a lack of food. There are several ways to identify adults who are malnourished or at risk of malnutrition, for example, the Malnutrition Universal Screening Tool MUST tool. MUST has been designed to identify adults, and especially older people, with malnourishment or a high risk of malnutrition.
If the person is at low risk of malnutrition, their overall score will be 0. A score of 1 denotes a medium risk and 2 or more indicates a high risk. MUST is only used to identify malnutrition or the risk of malnutrition in adults.
It will not identify specific nutritional imbalances or deficiences. Recommendations include ongoing screening at the hospital and at home. The person may undergo observation, their dietary intake will be documented for 3 days, and they will receive ongoing screening.
The person will need treatment from a nutritionist and possibly other specialists, and they will undergo ongoing care. The type of treatment will depend on the severity of the malnutrition, and the presence of any underlying conditions or complications. The healthcare provider will prepare a targeted care plan, with specific aims for treatment.
There will normally be a feeding program with a specially planned diet, and possibly some additional nutritional supplements. People with severe malnourishment or absorption problems may need artificial nutritional support, either through a tube or intravenously.
The patient will be closely monitored for progress, and their treatment will be regularly reviewed to ensure their nutritional needs are being met. A dietitian will discuss healthful food choices and dietary patterns with the patient, to encourage them to consume a healthy, nutritious diet with the right number of calories.
Those who are undernourished may need additional calories to start with. Regular monitoring can help ensure an appropriate intake of calories and nutrients. This may be adjusted as the patient's requirements change. Patients receiving artificial nutritional support will start eating normally as soon as they can.
To prevent malnutrition, people need to consume a range of nutrients from a variety of food types. There should be a balanced intake of carbohydrates , fats, protein, vitamins, and minerals, as well as plenty of fluids, and especially water. People with ulcerative colitis, Crohn's disease, celiac disease, alcoholism , and other health issues will receive appropriate treatment for their condition. Article last updated by Yvette Brazier on Mon 4 December All references are available in the References tab.
What you need to know. MNT is the registered trade mark of Healthline Media. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional. Privacy Terms Ad policy Careers. This page was printed from: Get the most out of Medical News Today.
Sign in Log in with your Medical News Today account to create or edit your custom homepage, catch-up on your opinions notifications and set your newsletter preferences.
Register for a free account Sign up for a free Medical News Today account to customize your medical and health news experiences. Register take the tour. Table of contents What is malnutrition? Symptoms Causes Diagnosis Treatment Prevention.