Clinical cases and Situational tasks Situational tasks

173. A person limits himself to products that contain phospholipids for a long period of time. Which metabolic disorders may this lead to?

Answer: When consumption of these products is limited, this may develop disorders such as fatty liver, increased blood cholesterol, atherosclerosis, disorders of the nervous system.

174. Analysis of the blood revealed a high content of cholesterol in -lipoproteidnye faction. What are the causes and possible implications for the body organism?

Answer: The reason for increase of -lipoproteins in blood may be a high-calorie diet with a predominance of carbohydrates, animal fats. This increases the risk of hypercholesterolemia, atherosclerosis, coronary heart disease, stroke and others

175. In person’s diet vegetable oil is absent. What may this lead to?

Answer: The consequence of the limited consumption of polyunsaturated fatty acids may reduce the phospholipids, increased cholesterol levels and disturbance of synthesis of prostaglandins and decreased activity of oxygen-reduction processes.

176. The concentration of phospholipids in the blood serum is 0.7 g / liter. What metabolic disorders can we observe?

Answer: Hypophospholipidemia. Normally, the contents of total phospholipids in the blood serum of 1,52-3,62 g / L (1,98-4,71 mmol / l). The reasons could be many disorders of liver, intestine, atherosclerosis and nutritional dystrophy.

177. Adult patient blood revealed a high concentrations of free fatty acids. What are the causes of this metabolic disorders?

Answer: The increase in blood free fatty acids observed in diabetes, starvation, or hyperproduction administration of adrenaline.

178. Why triglycerides are more efficient supply of energy then glycogen?

Answer: Triglycerides in their content have a lot of fatty acids. Fatty acids are the most restored compounds and their energy is higher (9 kcal / g) than glycogen (4 kcal / g), this is built from the remnants of glucose. Unlike fats, glycogen is highly hydrated. Thus, triglycerides contain 6 times more calories per 1 g than glycogen.

179. The patient is observed an allocation of undigested fat in the faeces. What are the possible causes for this?

Answer: The steatorrhea, the causes of which may be insufficient revenue in the intestine of bile acids, digestive disorders and absorption of lipids.

180. A Jewish couple of Eastern European descent presents to the clinic for prenatal counseling after their only child died early in childhood. The family could not remember the name of the disorder but said it was common in their ancestry. Their first child was normal at birth, a slightly larger than normal head circumference, an abnormal “eye finding,” and a severe progressive neurologic disease with decreased motor skills and eventually death. The autopsy is consistent with Tay-Sachs disease. What type of inheritance is this disorder? What is the biochemical cause of the disorder?

Answer: Inheritance: Autosomal recessive; 1:30 carrier rate in Ashkenazi Jews. Molecular basis of disorder: Lysosomal storage disorder with deficiency of hexosaminidase A enzyme resulting in GM2 gangliosides accumulating throughout the body. Tay-Sachs disease is a fatal genetic disorder where harmful amounts of lipids called ganglioside GM2 accumulate in the nerve cells and brains of those affected. Infants with this disorder appear normal for the first several months of life, and then as the lipids distend the nerve cells and brain cells, progressive deterioration occurs; the child becomes blind, deaf, and eventually unable to swallow. Tay-Sachs disease occurs mainly in Jewish children of Eastern European descent, and death from bronchopneumonia usually occurs by age 3 to 4 years. A reddish spot on the retina also develops, and symptoms first appear around 6 months of age. It is a lysosomal storage disorder with insufficient activity of the enzyme hexosaminidase A, which catalyzes the biodegradation of the gangliosides. The diagnosis is made by the clinical suspicion and serum hexosaminidase level. Currently there is no treatment available for this disease.

181. A couple is seen in your office for genetic counseling regarding Tay-Sachs disease. They are very knowledgeable and request more information about the specific enzyme that is defective in this disease. You explain that Tay-Sachs results from the lack of which of ezymes?

Answer: Tay-Sachs disease is the result of the lack of the enzyme β-Nacetylhexosaminidase.This enzyme hydrolyzes a terminal Nacetylgalactosamine

from the ganglioside GM2. This ganglioside is found in high concentrations in the nervous system and is normally degraded in the lysosome by the sequential removal of terminal sugars. The lack of β-N-acetylhexosaminidase results in the accumulation of the partially degraded ganglioside in the lysosome leading to significant swelling of the lysosome. The abnormally high level of lipid in the lysosome of the neuron affects its function resulting in the disease.

182. A 48-year-old male presents to the clinic because of concerns about heart disease. He reports that his father died from a heart attack at age 46, and his older brother has also had a heart attack at age 46 but survived and is on medications for elevated cholesterol. The patient reports chest pain occasionally with ambulation around his house and is not able to climb stairs without significant chest pain and shortness of breath. The physical exam is normal, and the physician orders an electrocardiogram (ECG), exercise stress test, and blood work. The patient’s cholesterol result comes back as 350 mg/dL (normal 200). The physician prescribes medication, which he states is directed at the ratelimiting step of cholesterol biosynthesis. What is the rate-limiting step of cholesterol metabolism? What is the class of medication prescribed?

Answer: Rate-limiting step: The enzyme hydroxymethylglutaryl-CoA reductase

(HMG-CoA reductase) catalyzes an early rate-limiting step in cholesterol biosynthesis. Likely medication: HMG-CoA reductase inhibitor, otherwise known as “statin” medications.

Hyperlipidemia is one of the most treatable risk factors of atherosclerotic vascular disease. In particular, the level of the low-density lipoprotein (LDL) correlates with the pathogenesis of atherosclerosis. Exercise, dietary adjustments,

and weight loss are the initial therapy of hyperlipidemia. If these are not sufficient,

then pharmacologic therapy is required. The exact LDL targets depend on the patient’s risk of cardiovascular disease. For example, if an individual has had a cardiovascular event previously (heart attack or stroke), the LDL target is 100 mg/dL; 1 to 2 risk factors without prior events = 130 mg/dL; and no risk factors = 160 mg/dL

183. A patient with hereditary type I hyperlipidemia presents with elevated levels of chylomicrons and VLDL triglycerides in the blood. What is the main function of the chylomicrons in circulation?

Answer: The liver and intestine are the main sources of circulating lipids. Chylomicrons carry triacylglycerides and cholesterol esters from the intestine to other target tissues. VLDLs carry lipids from the liver into circulation. Lipoproteins are a mix of lipids and specific proteins and these complexes are classified based on their lipid/protein ratio. Lipoprotein lipases degrade the triacylglycerides in the chylomicrons and VLDLs with a concurrent release of apoproteins. This is a gradual process which converts the VLDLs into IDLs and then LDLs.