1Biochemistry SpottersBiochemistry for Medics Biochemistry For Medics 11/18/2012www.namrata.coCompiled from-BIOCHEMISTRY FOR MEDICSThe Ultimate Group for Biochemistry StudentsJoin the group---www.facebook.com/groups/biochem4medics/
2 Biochemistry For Medics 11/18/2012Case study A morbidly obese woman decides to see her physician to begin a weight loss program. He tells her that diet and exercise play an essential role in her program. She is concerned that she does not have time to devote to exercise and wants to know if there is any pharmacologic treatment for her. The physician decides to start her on Orlistat which directly inhibits absorption of fats. Which of the following steps is directly inhibited by Orlistat ? A) bile salt formation B) Micelle formation C) Pancreatic and gastric lipase D) Absorption of Free fatty acids E) Chylomicron formation
3 Biochemistry For Medics 11/18/2012Answer to case study C)-Orlistat inhibits gastric and pancreatic lipases, preventing the digestion and absorption of fats. The normal sequence of digestion is that triglycerides are emulsified by bile salts. These are then acted on by lipases. The product of digestion are absorbed and reesterified in the intestinal mucosal cells to form triglycerides which are packed in the chylomicrons for transportation out to the peripheral cells for utilization. Under the effect of orlistat triglycerides are left undigested and unabsorbed, resulting in bulky stools. Over a period of time, orlistat therapy can induce deficiency of fat soluble vitamins.
4 Biochemistry For Medics 11/18/2012Case study A young man with normocytic anemia, jaundice, and splenomegaly was diagnosed as having RBC pyruvate kinase deficiency after a peripheral blood smear showed spiculated cells. Since in this patient pyruvate kinase is abnormal not only is less pyruvate made but intermediates above pyruvate in the glycolytic pathway build up slowing the pathway. Which of the following products may not be made in the appropriate amounts in the RBC because of the deficiency of pyruvate? A) Glucose B) Oxaloacetate C) Acetyl-CoA D) Lactate
5 Biochemistry For Medics 11/18/2012Answer to case study D)- The RBCs have no mitochondria so glucose cannot be made from pyruvate or acetyl-CoA or Oxaloacetate. The RBCs do have lactate dehydrogenase and conversion to lactate depends on pyruvate levels.
6 Biochemistry For Medics 11/18/2012Case study Which of the following complications is less likely to occur in type II diabetics, as opposed to type I diabetics? A) Retinopathy B) Weight gain C) Cardiovascular disease D) Hypoglycemic coma
7 Biochemistry For Medics 11/18/2012Answer to case study D)- Hypoglycemia is a common complication associated with over supplementation of type I diabetics with insulin. This is less common in type II diabetics, because insulin therapy generally occurs only in the later stages of the pathogenesis of this disease. Retinopathy, cardiovascular disease, and neuropathy are common complications associated with both forms of diabetes mellitus. In contrast to type I diabetics, type II diabetics tend to be overweight. Whether weight gain is a cause or consequence of disease progression is under current debate.
8 Biochemistry For Medics 11/18/2012Case studyAfter excessive drinking overan extended period of timewhile eating poorly, a middle-aged man is admitted to thehospital with “high output”heart failure. Which of thefollowing enzymes is mostlikely inhibited?A) AconitaseB) Citrate synthaseC) Isocitrate dehydrogenaseD) α-KetoglutaratedehydrogenaseE) Succinate thiokinase
9 Biochemistry For Medics 11/18/2012Answer to case study D)-This patient has exhibited symptoms of beri beri heart disease, which is a result of a nutritional deficiency in vitamin B1 (thiamine). The active form of the vitamin, thiamine pyrophosphate, is a required cofactor for α- ketoglutarate dehydrogenase.
10 Biochemistry For Medics 11/18/2012 Case studyWhich of the following is leastlikely to contribute to thehyperglycemia associated withuncontrolled type I diabetes?A) Decreased skeletal muscleglucose uptakeB) Decreased adipose lipogenesisC) Increased adipose lipolysisD) Increased hepaticgluconeogenesisE) Increased skeletal muscleglycogenolysis
11 Biochemistry For Medics 11/18/2012Answer to case study E) Unlike the liver, skeletal muscle cannot export glucose into the circulation. Once glucose enters the myocyte, it is destined for use by that cell. Thus, intramyocellular glycogen is used as a fuel source by skeletal muscle and therefore cannot contribute to the hyperglycemia observed in uncontrolled type I diabetes. In contrast decreased insulin mediated glucose utilization by skeletal muscle and adipose will contribute to hyperglycemia, as will decreased insulin-mediated suppression of hepatic glucose output. Decreased insulin-mediated suppression of lipolysis will indirectly contribute to hyperglycemia, by providing alterative, nonglucose, fuels (fatty acids and ketone bodies) or organs such as skeletal muscle and the liver.
12 Biochemistry For Medics 11/18/2012Case studyA 3-year-old Caucasian female presents with chronicdiarrhea and a failure to thrive. Stools were oily.History reveals that she was breastfedand had no problems until she was weaned. Whichof the enzymes would be expected to bedeficient following stimulation withsecretin?A) Cholesteryl esteraseB) Gastric lipaseC) Hormone sensitive lipaseD) Lipoprotein lipaseE) Pancreatic lipase
13 Biochemistry For Medics 11/18/2012Answer to case study E) Neither hormone sensitive lipase nor lipoprotein lipase is a digestive enzyme. The patient’s symptoms are consistent with an inability to absorb triglycerides, which would eliminate Cholesteryl esterase from consideration. Since the patient did not have any problem while being breast-fed, then the most likely enzyme to be deficient is pancreatic lipase, since gastric lipase is most active on short chain triglycerides, such as those that are found in breast milk.
14 Biochemistry For Medics 11/18/2012Case studyA gall stone that blocked theupper part of the bile duct wouldcause increase in which of thefollowings ?A) The excretion of fats in thefecesB) Formation of chylomicronsC) Excretion of bile saltsD) Conjugation of bile acidsE) Recycling of bile salts
15 Biochemistry For Medics 11/18/2012Answer to case study A) The right answer is excretion of excess fats in the feces, In this situation, bile salts cannot enter the digestive tract, therefore recycling and excretion of bile salts, digestion of fats, and formation of chylomicrons are decreased. As a consequence fats in the feces are increased (Steatorrhea).
16 Biochemistry For Medics 11/18/2012Case study A young infant, who was nourished with a synthetic formula, had a sugar in the blood and urine. This compound gave a positive reducing sugar test but was negative when measured with glucose oxidase(specific test for detection or estimation of Glucose). Treatment of blood and urine with acid (which cleaves glycosidic bonds) did not increase the amount of reducing sugar measured. Which of the following compounds is most likely to be present in this infants blood and urine ? A) Glucose B) Fructose C) Maltose D) Sorbitol E) Lactose
17 Biochemistry For Medics 11/18/2012Answer to case study B) The right answer is fructose. Glucose can not be there since specific test is negative. Sorbitol is non reactive to reduction test. Maltose and lactose would have caused increase in the amount of reducing sugar upon acid hydrolysis. Hence it is fructose which is reducing in nature nut non reactive to glucose oxidase.
18 Biochemistry For Medics 11/18/2012Case studyA 71-year-old man had a 3 week historyof weakness, polyuria, intense thirst,difficulty in speaking and understandingcommands, staggering walk, confusionand a weight loss of 10 kgs. For onemonth he took 200,000 units of vitaminD each day because he had severeosteoarthritis. His plasma calcium was3.38 mmol/L(13.5 mg/dl)What is the most probablediagnosis?
19 Biochemistry For Medics 11/18/2012Answer to case study It is a case of vitamin D toxicity. Usually, vitamin D toxicity results from taking excessive amounts. Because synthesis of 1,25(OH)2D (the most active metabolite of vitamin D) is tightly regulated, vitamin D toxicity usually occurs only if excessive doses (prescription or megavitamin) are taken. Marked hypercalcemia commonly causes symptoms. Anorexia, nausea, and vomiting can develop, often followed by polyuria, polydipsia, weakness, nervousness, pruritus, and eventually renal failure. Proteinuria, urinary casts, azotemia, and metastatic calcifications (particularly in the kidneys) can develop. Diagnosis is typically based on elevated blood levels of 25(OH)D. Treatment consists of stopping vitamin D, restricting dietary Ca, restoring intravascular volume deficits, and, if toxicity is severe, giving corticosteroids or bisphosphonates.
20 Biochemistry For Medics 11/18/2012Case study A 40 -year-old woman presented with chest pain. Her blood biochemistry report did not reveal significant changes and ECG was also normal. Her family history was positive for IHD. She was kept under observation and was discharged later after a few hours. She was advised to start a low dose of Aspirin. Aspirin is considered cardio protective, since it inhibits cyclo - oxygenase (COX) enzyme. COX is required for the production of which of these ? A) Thromboxane from arachidonic acid B) Leukotrienes from Arachidonic acid C) Phospholipids from Arachidonic acid D) Arachidonic acid from Linoleic acid E) Linolenic acid from Arachidonic acid
21 Biochemistry For Medics 11/18/2012Answer to case study A) Aspirin irreversibly acetylates cyclo-oxygenase-1 of platelets and inhibits the enzyme so that Thromboxane (TxA2) is not formed. So there is no vasoconstriction and no platelet aggregation and hence the thrombus formation is prevented. At the same time Aspirin also inhibits production of Prostacyclin (PGI2) by endothelial cells, which prevents platelet aggregation and produces vasodilatation. But unlike platelets, the endothelial cells regenerate cyclo- oxygenase within a few hours. Thus the overall balance shifts towards prevention of thrombus formation by promoting the Prostacyclin formation. Aspirin is clinically used for the prevention and management of Angina. Myocardial infarction, Stroke and Transient Ischaemic attacks (TIA).
22 Biochemistry For Medics 11/18/2012Case studyA 23-year-old, boxing contenderpresents with assorted metabolicdisorder , most notably ketosis.During the history and physicalexamination, he describes histraining regimen, involves consuminga dozen raw eggs a day for protein.Raw eggs contain a protein calledAvidin, with an extremely highaffinity for a cofactor required for thepropionyl co A carboxylase andAcetyl co A carboxylase. Name thecofactor which gets deficient byconsumption of raw eggs.
23 Biochemistry For Medics 11/18/2012Answer to case study The right answer is Biotin. Egg white contains Avidin, that binds with high affinity to Biotin. Biotin is the cofactor required for conversion of Propionyl co A to D-Methyl malonyl co A and also for the conversion of Acetyl co A to Malonyl co A. Consumption of raw eggs promotes formation of Avidin- Biotin complex causing Biotin deficiency, known as Egg white injury. The said complex is not formed if the same number of cooked eggs are ingested, since cooking causes denaturation of Avidin and that loses the ability to bind with biotin.
24 Biochemistry For Medics 11/18/2012 Case studyAn infant is born with a high forehead,abnormal eye folds, and deformed ear lobes.He shows little muscle tone and movement.After multiple tests, he is diagnosed withZellweger syndrome, a disorder cause bymalformation of peroxisomes.Which of the following is expected tobe high in concentration in brain tissueof the affected individual ?A) Ketone bodiesB) LactateC) CholesterolD) Very long chain fatty acids
25 Biochemistry For Medics 11/18/2012Answer to case study D) The right answer is "Very long chain fatty acids". Very long chain fatty acids are first trimmed in the peroxisomes till the length of C16 or C18, then they are transported to mitochondria in the conventional way though carnitine shuttle to be oxidized completely by beta oxidation. In Zellweger syndrome the Peroxisomal trimming is impaired, thus VLFA accumulate in brain and blood of affected patients.
26 Biochemistry For Medics 11/18/2012Case studyAn 18 month-old- child is leftunattended while in thekitchen and ingests a smallportion of rat poison found inthe cupboard found underthe sink. The ingredientfluoroacetate reacts withOxaloacetate to formfluorocitrate. Whichpathway of the body isinhibited by this poison ?
27 Biochemistry For Medics 11/18/2012Answer to case study TCA Cycle is inhibited by Fluoroacetate Fluoroacetate first gets converted to Fluoroacetyl coA then condenses with Oxaloacetate to get converted to Fluoro citrate to inhibit Aconitase enzyme of TCA cycle. It is an example of suicidal inhibition.
28 Biochemistry For Medics 11/18/2012Spot Question High carbohydrate ingestion leads to obesity, What are the two most important causes ?
29 Biochemistry For Medics 11/18/2012Answer to spot question Excessive carbohydrate consumption leads to obesity- 1) Excess glucose available- two main pathways of glucose utilization provide precursors for lipogenesis A) HMP pathway- Provides NADPH for reductive biosynthesis B) Glycolysis- Provides Acetyl co A and Glycerol-3-p a) Excess of Pyruvate from glucose- Excess of Acetyl co A - Excessive fatty acid synthesis b) Excess of glycerol-3-p - available from Dihydroxy acetone Phosphate Esterification of Glycerol-3-P with fatty acids to form Triglycerides- Increased adipose mass and hence Obesity.
30 Biochemistry For Medics 11/18/2012Case studyA 40-year-old, obese woman presents withacute pain in the right upper quadrant of herabdomen as well as vomiting. She isdiagnosed with gall stones and is placed onursodeoxycholate, a bile salt used to inhibitthe formation of cholesterol gall stones byfacilitating dissolution of cholesterol.Which of the following is also a bilesalt ?A) HMG Co AB) MevalonateC) LanosterolD) SqualeneE) Glycocholate
31 Biochemistry For Medics 11/18/2012Answer to case study E) The right answer is Glycocholate. Bile salts and phospholipids keep cholesterol in the soluble form. Any condition that causes less bile salt or more cholesterol formation leads to precipitation of cholesterol . Initially crystals are formed which upon accumulation from stones. Synthetically prepared bile salt, ursodeoxy cholic acid is given for dissolution of cholesterol stones to those patients who do not want surgery or are not fit for surgery. Cholecystectomy is the ultimate cure for symptomatic gall stones. In majority of cases gall stones do not cause symptoms.
32 Biochemistry For Medics 11/18/2012Case study A 65 year-old man with a long history of diabetes presents to his physician after failing the drivers license renewal eye examination. Patients with diabetes have abnormally high blood glucose levels. Glucose can enter the lens of the eye, where it can be converted to Sorbitol. Which of the followings converts glucose to Sorbitol ? A) Hexokinase B) Aldose reductase C) Sorbitol dehydrogenase D) Aldose oxidase E) Glucokinase
33 Biochemistry For Medics 11/18/2012Answer to case study B) Aldose reductase is the right answer. Hexokinase and Glucokinase are enzymes for phosphorylation of glucose in the pathway of glycolysis and sorbitol dehydrogenase is an enzyme to convert sorbitol to fructose. It is absent in most of the tissues except for liver, seminal epithelium and testicular tissue. Aldose oxidase has no role to play. Had Sorbitol dehydrogenase been there in all tissues, diabetes related complications would not have occurred, though this is not the only mechanism responsible for causing complications but a major contributor. Aldose reductase is the enzyme responsible for conversion of glucose to Sorbitol.
34 Biochemistry For Medics 11/18/2012Case Study A 38-year- old woman sees an advertisement for a new weight loss medication. The ad claims that the drug causes your body to burn calories without having to exercise. In theory which of the following compounds could make this claim? A) Rotenone B) Antimycin C) Dinitrophenol D) Amytal E) Atractyloside
35 Biochemistry For Medics 11/18/2012Answer to case study C)The right answer is Dinitrophenol. The mechanism of action of the drug is through uncoupling of oxidative phosphorylation and Dinitrophenol is the only uncoupler in the list, rest all inhibitors of ETC except, Atractyloside which is an inhibitor of ATP/ADP transporter.
36 Biochemistry For Medics 11/18/2012Case study A known alcoholic is found lying semiconscious at the bottom of a stairwell with a broken arm by his land lady, who called an ambulance to take him to the emergency room. Initial laboratory studies showed are relatively large anion gap of 34 (normal = 9 to 15). His blood alcohol was elevated at 245 mg/dL (intoxication level = 150 to 300 mg/dL), and his blood glucose was 38 mg/dL (low normal). The patient/s large anion gap and hypoglycemia can best be explained by which of the following? A) Decreased secretion of glucagon B) Increased secretion of insulin C) Increased urination resulting from the diuretic effect of alcohol D) Inhibition of dehydrogenase enzymes by NADH E) Inhibition of glycogenolysis by ethanol
37 Biochemistry For Medics 11/18/2012Answer to case study D. Alcoholics frequently do not eat while binge drinking, so it is most likely that his liver glycogen stores became depleted and could not increase his blood glucose levels. The metabolic stress leads to the increase in secretion of epinephrine and other hormones that mobilize fatty acids from stored triglycerides in adipose cells. These fatty acids undergo β-oxidation in the liver but are converted to ketone bodies because of the inhibition of the TCA cycle by high levels of NADH produced by the oxidation of ethanol first to acetaldehyde and acetate. Key gluconeogenic dehydrogenases are also inhibited by the elevated levels of NADH, including lactate dehydrogenase, glycerol 3-phosphate dehydrogenase, and malate dehydrogenase.