Q: About a patient with Gaucher disease

Question about Lipid Metabolism (LM-03)


                                           autosomal recessive disorder wikipedia


A Russian Jewish mother presents to your office with a very pale child. The physical exam shows massively enlarged liver and spleen and extensive skeletal disease. Lab exams show anemia and low blood platelets.


Because of your findings and the fact that the child is an Ashkenazi Jewish girl, you suspect it could be a Gaucher Disease, so you refer the patient for a liver biopsy.


You expect that the results of the biopsy will confirm your diagnosis of this autosomal recessive disorder, and thus, it will  show an accumulation of sphingolipids in liver cells, as a consequence of a deficit of :


a)     a cytosol enzyme


b)     a lipoprotein lipase


c)      a liver hormone sensitive lipase


d)     a lysosomal enzyme


e)     a mitochondrial enzyme


f)       a peroxisomal enzyme





Van Gogh’s medical condition: a biochemical disorder?



The disease that aflicted him has been object of discussion during many years:  absinthe intoxications, arsenite poisoning, bipolar disorder, epilepsy, Lead poisoning, Meniere’s disease, Syphilis, have been among the atributted causes of his symptoms and signs.

We have talked already about the arsenite poisoning hypothesis.

Since Vincent Van Gogh’s life and medical condition have been presented in at least 5 major films, and I have already a thread about Porphyria in the movies, I invite you to read the basis that supports that Vincent Van Gogh suffered from Porphyria in the Biochemistry at the movies page.

Q: About Newborn metabolism (CM-05)

                                               from timtom.ch, in flickr




It is very important to feed the baby very soon after birth, because during the first few hours after birth the enzyme phosphoenolpyruvate carboxykinase is present in very low amounts, and this fact compromise:


a) gluconeogenesis


b) glucose phosphorylation


c) glycogenesis


d) glycogenolysis


e) glycolysis



Calculating calories in meals


Answer to Biochemistry Question N-02: (e) 500 Calories



                                      from zamber on flickr



Since usually we use large amounts of energy compared to the calorie unit used in Physics, the calorie unit used in Nutrition is different to the classical calorie definition used in Physics. While in Physics 1 calorie is defined as the quantity of energy necessary for increasing the temperature of one gram of water 1 Celsius degree at 1 atmosphere of pressure, the nutritional calorie correspond to 1000 this value (in a more accurate way, it correspond to what is called a large calorie, in contrast to the  classical “small” calorie of Physics, and should be abbreviated as Cal). It means, that 1 Nutritional calorie is equivalent to 1 kilocalorie in physics.


In the SI unit 1 physics’ calorie is equivalent to 4.184 joules, so a Nutritional calorie is equivalent to 4 184 Joules.



The body needs energy for:


1.- Mantaining Resting Metabolic Rate (RMR, former BMR)


2.- Heat production  (An important factor in heat production is the thermic effect of food, or diet induced thermogenesis, that may amount 5-10 %  of total energy expenditure/day)


3.- Physical activity



The human body obtain the energy it needs from the foods.


The major dietary energy sources:



4 cal/g  (nutritional calorie)


9 cal/g (nutritional calorie)


4 cal/g (nutritional calorie)



As you can see, fat is the most concentrated source of energy – weight for weight it provides just over twice as much as either protein or carbohydrate.


Alcohol provides almost as much energy as fat: 1 gram of alcohol can supply 7 cal/g . For some people alcoholic drinks form a large part of their energy intake. This can be harmful to health since a high alcohol consumption is a risk factor for several diseases.


The energy content of a food or drink depends on how many grams of carbohydrate, fat, protein and/or alcohol are present.


Since the source of energy in the diet has been implicated as a risk factor in certain diseases, it has been described a recommended distribution of calories in diet. The Acceptable Macronutrient Distribution Range (AMDR) has been defined as the range of intake for a particular energy source that is associated with reduced risk of chronic disease while providing intakes of essential nutrients (Dietary Guideline for Americans, Glossary . The caloric composition of diet should be approximately, 45-65 % from carbohydrates, 20-35 percent from fats and 10-35 % from proteins, but there are recommendations for specific groups.


Different websites show the caloric value of thousands of foods. This is one of those sites with several related links:  http://www.caloriecountercharts.com/



Anyway, it is important that you know the general principles described above.


USMLE released sample questions, that exemplify contents of the examination, have included questions about caloric calculation in past years (Ex: Question 45 in 2005 USMLE Step I Content Description and Sample Test, that also appears as Question 35 in the 2006 edition). Unfortunately, copyright issues do not allow us to reproduce that question here.



More information can be found in:


A classic:

Merrill, A.L.; Watts, B.K. :Energy values of food: Basis and derivations


Food composition and Nutrition Links from the USDA



Isoenzymes or Isozymes


Answer to Enzyme Question E-04


Answer (b) isozymes


                                           Lactate Dehydrogenase LDH1  (MMMM)




                             Lactate Dehydrogenase (LDH M4)


Isozymes or Isoenzymes are proteins with different structure which catalyze the same reaction. Frequently they are oligomers made with different polypeptide chains, so they usually differ in regulatory mechanisms and in kinetic characteristics.


From the physiological point of view, isozymes allow the existence of similar enzymes with different characteristics, “customized” to specific tissue requirements or metabolic conditions.


One example of the advantages of having isoenzymes for adjusting the metabolism to different conditions and/ or in different organs is the following:


Glucokinase and Hexokinase are typical examples of isoenzymes. In fact, there are four Hexokinases: I, II, III and IV. Hexokinase I is present in all mammalian tissues, and Hexokinase IV, aka Glucokinase, is found mainly in liver, pancreas and brain.


Both enzymes catalyze the phosphorylation of Glucose:


Glucose + ATP —–à Glucose 6 (P) + ADP


Hexokinase I has a low Km and is inhibited by glucose 6 (P).  Glucokinase is not inhibited by Glucose 6 (P) and his Km is high. These two facts indicate that the activity of glucokinase depends on the availability of substrate and not on the demand of the product.


Since Glucokinase is not inhibited by glucose 6 phosphate, in conditions of high concentrations of glucose this enzyme continues phosphorylating glucose, which can be used for glycogen synthesis in liver. Additionally, since Glucokinase has a high Km, its activity does not compromise the supply of glucose to other organs; in other words, if Glucokinase had a low Km, and since it is not inhibited by its product, it would continue converting glucose to glucose 6 phosphate in the liver, making glucose unavailable for other organs (remember that after meals, glucose arrives first to the liver through the portal system).


Since isoenzymes have different tissue distributions, their study is an important tool in assessing the damage to specific organs.


Examples of the diagnostic use of isoenzymes are the study of Lactate Dehydrogenase and Creatine Kinase.



Lactate Dehydrogenase (LDH)


It is formed by the association of five peptide chains of two different kinds of monomers: M and H


The variants seen in humans are:


LDH1: M M M M (abundant in heart, brain erythrocytes; around 33% of serum LDH)


LDH2: M M M H (abundant in heart, brain erythrocytes; around 45% of serum LDH)


LDH3: M M H H (abundant in brain, kidneys, lung; around 18 % of serum LDH)


LDH4: M H H H ((abundant in liver, skeletal muscle, kidney; around 3% of serum LDH)


LDH5: H H H H ((abundant in liver, skeletal muscle, ileum; around 1 % of serum LDH)



In myocardial infarction, Total LDH increases, and since heart muscle contains more LDH1 than LDH2, LDH1 becomes greater than LDH2 between 12 and 24 hours, after the infarction, so the ratio LDH1/LDH2 becomes higher than 1 and will stay flipped for several days.


 An increase of LDH 5 in serum is seen in different hepatic pathologies: cirrhosis, hepatitis and others. An increase of LDH5 in heart diseases usually indicates secondary congestive liver involvement.


Creatine Kinase :



Creatine Kinase (CK) aka Creatine phosphokinase (CPK) is a similar example: three isoenzymes formed by combinations of different subunits:


CK1 (BB) is abundant in brain and smooth muscle (practically absent form serum)

CK2 (MB) is abundant in cardiac muscle, some in skeletal muscle (practically absent from serum)

CK3 (MM) is abundant in skeletal muscle and cardiac muscle (practically 100 % of serum CK)






                                                                       Creatine Kinase CK3



They can be differentiated based on their different electrophoretic mobility.


The primary clinical use of CK studies is the diagnosis of Myocardial Infarction,

(increased in the MB variant), but CK is also increased in different conditions

as muscular diseases and traumas (MM and MB) and brain trauma and brain surgery (BB). 


CK2 appears in serum within 6 hours after the myocardial infarction and is cleared after 24 to 48 hours. A persistence of CK2 in serum indicates extension of the infarction to other areas or another infarction.



For more information, please read:





The Medical Biochemistry page: Enzymes in the diagnosis of pathology.


Sacher, S. R and McPherson, R.A.:

Widmann’s Clinical Interpretation of laboratory Tests.

11th Edition. 2000 F.A Davis Company, Philadelphia, PA


Lactate Dehydrogenase


Creatine Kinase


Clinical Methods: The Clinical, Physical and Laboratory Investigations. Creatine Kinase



Q: Pentose phosphate Pathway and Thiamine Deficiency

Biochemistry Question CM-04 about Carbohydrate Metabolism



                            Derek Farr in Flickr


                               (Artist: Tim Burke, Detroit; photo source:  Derek Farr in Flickr)


C. W., a 60 year-old male chronic alcoholic patient, is taken to the emergency department in a hypoglycemic coma. After appropriate treatment to correct the hypoglycemia, you realize that the patient show signs of malnutrition, so you will begin a treatment for it. Which of the following enzymes of the Pentose phosphate Pathway can be used to test for a thiamine deficiency?


a)     Aldolase


b)     Glucose 6 (P) dehydrogenase


c)      Phosphogluconate dehydrogenase


d)     Phosphopentose epimerase


e)     Phosphopentose isomerase


f)       Transaldolase


g)     Transketolase




Moviecular Biology Page Updated: Jurassic Park



John Hammonds: “- All major theme parks have had delays. When they opened Disneyland in 1956, nothing worked, nothing!”


Dr. Ian Malcolm– “But John, but if the Pirates of the Caribbean breaks down, the Pirates do not eat the tourists.”







“If there is one thing the history of evolution has taught us it’s that life will not be contained. Life breaks free, expands to new territory, and crashes through barriers, painfully, maybe even dangerously.”




Is the premise of the dinosaur’s DNA obtained from the mosquito possible?


What is the Lysine Contingency?


Visit the updated Moviecular Biology page!