Рũßłїѕђёď åŗțїćłё #2

 Mattar et al. 2012. ‘Lactose intolerance: diagnosis, genetic and clinical factors.’ Accessed March 28, 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401057/

Lactose intolerance: diagnosis, genetic and clinical factors:

Lactose is a carbohydrate found in milk. This disaccharide is made up of glucose and galactose subunits. Seventy five percent of the world’s population loses their ability to breakdown the disaccharide into monosaccharide units that are easily digested. Lactase is the enzyme that breaks down lactose products. In infants breakdown is at its max from birth till 2 years. An aging person can fall into a group of lactase non-persistence (hypolactasia) or lactase-persistence activities. Reduction in lactose renders persons lactose intolerant that develop symptoms in identifying the presence of this diagnosis. 

            Individuals with hypolactasia and lactase persistence have identical coding sequences which were confirmed in a study where DNA was collected from subjects in various parts of the world. The LCT-13910CT and LCT-13910TT genotypes were associated with the lactase-persistence phenotype. This indicates that it dominates the person where they is a lactose digester. If the genotype was LCT- 13910CC and LCT-13910T is absent the person suffers from lactose mal digestion.

            The first method for detection of lactose mal digestion was direct biochemical assay of lactase activity from a jejunal sample. This was performed using a glucose oxidase reagent which detects glucose molecules present in the lactose. This method has been replaced by endoscopic duodenal biopsy. The lactose breath test is also a method for determining the presence of lactose in the body. It is based on fermentation of undigested lactose by intestinal flora producing hydrogen, carbon dioxide and methane which is absorbed and eliminated via the lungs. The result of these gases is bloating, abdominal pain, and diarrhea. Undigested lactose acidifies the colon and increases diarrhea while some may experience constipation.

            A false-negative result can occur if antibiotics have been recently consumed within one month of testing or if the pH is too acidic to inhibit bacterial activity or if there has been bacterial growth. The genetic test provides a more direct result where hypolactasia or lactase persistence genotype is found. This was formed due to the discovery of lactase-persistence alleles. This method was deemed better than the breath test since there is no cut off level or dependence on the amount of lactose or influenced by the duration of the test and age of the individual.

            Individuals suffering with this problem need to maintain their intake of calcium due to their restricted milk diet. A deficient in calcium result in bone diseases. A key to management of lactose intolerance is a recommended of no more than 20g of lactose without significant symptoms. A person’s diet changes where they would have to consume it with other foods and prevent lactose tablets. Supplements of calcium and vitamin D are produced which may be expensive to the consumer.  Yoghurt containing live cultures providing endogenous beta galactosidase is an alternative source of calories and calcium and is well tolerated by many lactose-intolerant patients. Lactose hydrolyzed milk is another safe source for patients.

            This article cleared up the effects of an individual suffering from the absence of the enzyme called lactase which breaks down lactose found in dairy products such as milk. It enhances the symptoms of a patient suffering from lactose intolerance and deals with the different mechanisms of detecting lactose in the body and suggests which method is better due to the information gathered.

            Hope you learned something as well…



One of this week’s topic is the TCA cycle. It occurs after glycolysis, where 2 molecules of pyruvate is generated. This pyruvate is converted to acetyl – CoA via a linked reaction between glycolysis and the Kreb’s cycle. Five cofactors are involved in this conversion which are: CoA-SH, NAD+, TPP, lipoate and FAD. In this process NAD+ is used and NADH is generated. The following diagram shows the various steps in this cycle.



The Krebs cycle, also called the citric acid cycle, is a fundamental metabolic pathway involving 8 enzymes essential for energy production through aerobic respiration. This pathway is also an important source of biosynthetic building blocks used in gluconeogenesis, amino acid biosynthesis, and fatty acid biosynthesis. The Krebs cycle takes place in mitochondria where it oxidizes acetyl-CoA, releasing carbon dioxide and extracting energy primarily as the reduced high-energy electron carriers NADH and FADH2. NADH and FADH2 transfer chemical energy from metabolic intermediates to the electron transport chain to create a different form of energy, a gradient of protons across the inner mitochondrial membrane. The energy of the proton gradient in turn drives synthesis of the high-energy phosphate bonds in ATP. An acetyl-CoA molecule (2 carbons) enters the cycle when citrate synthase condenses it with oxaloacetate (4 carbons) to create citrate (6 carbons). One source of the acetyl-CoA that enters the Krebs cycle is the conversion of pyruvate from glycolysis to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA is a key metabolic junction, derived not only from glycolysis but also from the oxidation of fatty acids. As the cycle proceeds, the Krebs cycle intermediates are oxidized, transferring their energy to create reduced NADH and FADH2. The oxidation of the metabolic intermediates of the pathway also releases two carbon dioxide molecules for each acetyl-CoA that enters the cycle, leaving the net carbons the same with each turn of the cycle. This carbon dioxide, along with more released by pyruvate dehydrogenase, is the source of CO2 released into the atmosphere when you breathe. The Krebs cycle is regulated to efficiently meet the needs of the cell and the organisms. The irreversible synthesis of acetyl-CoA from pyruvate by pyruvate dehydrogenase is one important regulatory step and is inhibited by high concentrations of ATP that indicate abundant energy. Citrate synthase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase are all key regulatory steps in the cycle and are each inhibited by abundant energy in the cell, indicated through high concentrations of ATP or NADH. The activity of the Krebs cycle is closely linked to the availability of oxygen although none of the steps in the pathway directly use oxygen. Oxygen is required for the electron transport chain to function which recycles NADH back to NAD+ and FADH2 back to FADH, providing NAD+ and ADH required by enzymes in the Krebs cycle. If the oxygen supply to a muscle cell or a yeast cell is low NAD+ and FADH levels fall and the Krebs cycle cannot proceed forward so the cell must resort to fermentation to continue making ATP. Some Krebs cycle enzymes require non-protein cofactors for activity such as thiamine, vitamin B1. Insufficient quantities of this vitamin in the diet leads to decreased activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase and a decrease in the ability of the Krebs cycle to meet metabolic demands causing the disease beriberi.






It is a rare genetic metabolic disorder that affects an individual’s ability to metabolize the sugar galactose properly. There are three forms of this disease Galactose-1-phosphate uridyl transferase deficiency, Galactokinase deficiency or Galactose-6-phosphate epimerase deficiency.

Infants with galactosemia can develop symptoms in the first few days of life if they eat formula or breast milk that contains lactose. The symptoms may be due to a serious blood infection with the bacteria E. coli.

  • convulsions
  • irritability
  • poor feeding habits where the baby refuses to eat formula containing milk
  • poor weight gain
  • yellow skin and whites of the eyes (jaundice)
  • vomiting

gal 1

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The above photo indicates that the absence of the GALT enzyme leads to health problems as indicated above.





What is Hemolytic Anemia?

It is a condition in which red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over. Hemolytic anemia occurs when the bone marrow is unable to replace the red blood cells that are being destroyed. Hemolytic anemia is a type of anemia. The term “anemia” usually refers to a condition in which the blood has a lower than normal number of red blood cells.

You may not have symptoms if the anemia is mild. If the problem develops slowly, the first symptoms may be:

  • Feeling grumpy
  • Feeling weak or tired more often than usual, or with exercise
  • Headaches
  • Problems concentrating or thinking

If the anemia gets worse, symptoms may include:

  • Blue color to the whites of the eyes
  • Brittle nails
  • Light-headedness when you stand up
  • Pale skin color
  • Shortness of breath

  • Sore tongue

Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) is an enzyme in the pentose phosphate pathway – a metabolic pathway that supplies reducing energy to cells such as erythrocytes by maintaining the level of the   co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance  G6PD reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH while oxidizing glucose-6-phosphate. This NAD needs to present for erythrocyes to survive by making its energy and completing glycolysis. 







Have you ever heard of Pompe disease? If you haven’t, it’s not a surprise. It’s estimated that only 10,000 people worldwide have it.



                          Pathophysiology of Pompe’s disease – it is also referred to as GAA deficiency. It is the result of a mutation in the gene that makes the enzyme alpha-glucosidase (GAA) and prevents the breakdown of glycogen. There is a buildup of lysosomal glycogen in the body’s cells and accumulation in tissues of the heart and skeletal muscles. Infants with this disorder experiences poor muscle tone, weakness, an enlarged liver, heart defects, breathing problems and enlarged tongues. Most babies die within a year.  The non-classic form appears at age one which has symptoms of delayed motor skills, muscle weakness and an abnormal, large heart. If diagnosed at a later age the symptoms are milder and do not involve the heart. They however experiences muscle weakness in the legs and difficult breathing which could lead to respiratory failure.

    Infants with rapidly progressive Pompe disease have muscle weakness which is shown by the characteristic head lag and frog-like posture of the legs.




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A family with the two younger children suffering from Pompe’s Disease:

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                                       Pathophysiology of Leigh’s disease – it is also known as Leigh’s syndrome. It is a genetic disorder that affects the central nervous system. It is caused by a defect or mutation in the mitochondrial DNA or by deficiencies of the enzyme pyruvate dehydrogenase.  The genetic mutations in mitochondrial DNA interfere with the energy sources (ATP) that triggers the brain and motor movements. The symptoms begin in infancy such as lack of head control and poor sucking ability. Following there is a loss of appetite, vomiting, prolonged crying, fits and irritability. The individual result in having poor muscle tone and is usually weak. There may be kidney and respiratory problems associated. Most cases of Leigh’s disease are fatal during childhood.

Pictures showing the effects of this disease:

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Pathophysiology of Tay-Sachs disease (TSD) – TSD also referred to as type one GM2-gangliosidosis is a genetic disorder caused by deficiency of the enzyme hexosaminidase A (hex-A) which results in a failure to process a lipid called GM2 ganglioside. Thus results in accumulated lipid in the brain, spleen and tissues. TSD begins in infancy where the child’s head control is lost by six to eight months of age. The infant cannot roll over or sit up. There is tightness of muscles and little flexibility. An excessive drooling and rapid contraction and relaxation of the muscles become evident. Blindness and head enlargement occur by the second year. The disease worsens as the central nervous system progressively deteriorates. Constant nurse care is needed after age two. The disease is a progressive development of retardation, paralysis, blindness and death by the age of three or four years.


Symptoms of Tay-Sachs Disease include:

– Slowed Development 

– Weakened Muscles 

– Loss of Motor Skills 
– Seizures 
– Vision and Hearing Loss 
– Mental Retardation 
– Paralysis 
– Cherry-Red Spot (eye abnormality) 


– Death by Early Childhood










                                         One of the most important aspects of a protein is its shape. The shape of a protein is critical to its function, and this holds true for hemoglobin. The shape of a protein is largely based on the amino acids it contains and whether or not they are charged, attracted to water or repelled by water. According to the sickle cell center at Harvard University, the amino acid substitution that causes sickle cell disease is a mutation of the sixth amino acid from glutamic acid to valine. This is relevant because glutamic acid is a charged amino acid and, as a result, is very attracted to water, whereas valine is repelled by water. This simple substitution occurs at a spot that is critical for the hemoglobin protein’s shape, causing it to have an unusual structure and to be poor at binding to oxygen. Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal sickle or crescent shape.

images (2)                          sickle-cell-anemia                  images (1)

Picture sowing the various areas                                                                                                                                 affected by sickle cell anemia

The effects of sickle cell anemia cause pain and damage to the organs. Irregularly shaped red blood cells become sluggish, and move more slowly, causing clumping. Red blood cells are normally round, and carry oxygen rich blood. Oxygen is carried by hemoglobin in red blood cells, but in individuals with sickle cell anemia, abnormal hemoglobin levels cause red blood cells to take on a C shape. Red blood cells that are abnormally shaped, as in sickle cell anemia, die before new ones can be produced.

Sickle cell anemia can destroy the organs of the body. Pain and swelling in the toes, feet and ankles might be one of the first signs of sickle cell anemia. Blocked blood vessels can also cause pain in the hands. Sickle cells can block blood flow to other organs, including the spleen, lungs, brain, eyes and the blood vessels that supply the heart and lungs. Infection and pneumonia are possible.
Eye damage, disability from hemorrhagic or ischemic stroke (from lack of oxygen to the brain), enlargement of the spleen, and pulmonary artery hypertension (increased pressure in the lungs) are possible effects of sickle cell anemia. Leg ulcers can occur from poor blood flow to the skin. Kidney failure can occur. Red blood cell destruction that releases too much bilirubin into the bloodstream can lead to gallstones and gallbladder attacks that cause nausea and abdominal pain.


A child suffering from sickle cell anemia


            As the daughter of a victim of sickle cell anemia from Madagascar, I spent my whole childhood with sickle cell disease without knowing its name, but aware of the suffering and the pain it causes. After the disease was diagnosed in my daughter a few years ago when she was two, I decided to dedicate myself to ensuring that families, mothers and patients no longer had to live through the hell of ignorance. So in 2008, we set up the first association to fight against sickle cell disease in Madagascar.

sicklecell-anemia-symptom                                                                                                   shortened finger

Treatment: There isn’t a cure for sickle cell anemia, but symptoms can be well-handled with treatment. Antibiotics are used by infections patients and  Hydroxyurea are used to manage pain and reduce simple crises. In severe cases, blood transfusions or bone marrow transplants may be performed.









There are three videos about patients coping with this disease which are informational.