Preparatory Guide on Biochemistry, Molecular Biology, Physiology, Microbiology, Immunology, Pharmacology & Drug Discovery
Collection of 1500 plus MCQs

Carbohydrate Metabolism: MCQ on Glycolysis &Gluconeogenesis

October 28, 2017
Multiple Choice Questions on Glycolysis, Gluconeogenesis, and Hexose sugar metabolism

1) Which of the following enzyme is not involved in galactose metabolism?
a) Glucokinase
b) Galactokinase
c) Galactose-1-Phosphate Uridyl transferase
d) UDP-Galactose 4- epimerase

2) Which of the following enzyme is defective in galactosemia- a fatal genetic disorder in infants?
a) Glucokinase
b) Galactokinase
c) Galactose-1-Phosphate Uridyl transferase
d) UDP-Galactose 4- epimerase

3) In the liver, the accumulation of which of the following metabolite attenuates the inhibitory of ATP on phosphofructokinase?
a) Glucose-6-Phosphate
b) Citrate
c) Fructose-1,6-Bisphosphate
d) Fructose-2,6-Bisphosphate

4) Mutation in which of the following enzymes leads to a glycogen storage disease known as Tarui’s disease?
a) Glucokinase
b)Phosphofructokinase
c) Phosphoglucomutase
d) Pyruvate Kinase

5) Erythrocytes undergo glycolysis for production of ATP. The deficiency of ……………. enzyme leads to hemolytic anemia?
a) Glucokinase
b)Phosphofructokinase
c) Phosphoglucomutase
d) Pyruvate Kinase

6) Cancer cells have high energy demands for replication and division. Increased flux of glucose into glycolysis replenishes the energy demand. Which of the following enzyme plays an important role in tumor metabolism?
a) Glucokinase
b)Phosphofructokinase
c) Phosphoglucomutase
d) Pyruvate Kinase M2

7) Which of the following glucose transporter (GLUT) are important in insulin-dependent glucose uptake?
a) GLUT1
b) GLUT2
c) GLUT3
d) GLUT4

8) Which of the following glucose transporter (GLUT) is present in beta cells of the pancreas?
a) GLUT1
b) GLUT2
c) GLUT3
d) GLUT4

9) Which of the following glucose transporter (GLUT) is important in fructose transport in the intestine?
a) GLUT1
b) GLUT3
c) GLUT5
d) GLUT7

10) Which of the following metabolite negatively regulates pyruvate kinase?
a) Fructose-1,6-Bisphosphate
b) Citrate
c) Acetyl CoA
d) Alanine

11) In absence of oxygen, pyruvate is converted into lactate in muscle because
a) Lactate is a substrate from the downstream pathway
b) Lactate acts as a substrate for the formation of the amino acid
c) during the product of lactate two ATP are produced
d) during lactate formation, NADH is reconverted into NAD.

12) Which of the following glycolytic enzyme is inhibited by the accumulation of long chain fatty acid in the liver?
a) Hexokinase
b) Glucokinase
c)Phosphofructokinase
d) Pyruvate kinase

13) Which of the following statement related to phosphofructokinase-I is false:
a) PFK-2 is the isoenzyme of PFK-1 that is present in the liver
b) PFK-1 is activated by AMP whereas inhibited by ATP and citrate
c) The binding of ATP to PFK-1 induces the conformation change from R to T state
d) PFK-1 is regulated by posttranslational modification such as phosphorylation

14) Which of the following statement about Phosphofructokinase-2 (PFK-2) is false?
a) PFK-2 is a bifunctional enzyme having kinase domain, phosphatase domain, and regulatory domain
b) Activated protein kinase A phosphorylates PFK-2 and activates phosphatase domain
c) PFK-2 catalyzes the conversion of fructose-6-phosphate to fructose 2-6 bisphosphate
d) PFK-2 phosphatase activity is activated by the insulin signaling pathway.

15) Which of the following hormone decreases blood glucose and increases uptake of glucose in various tissues like skeletal muscle, adipose tissues?
a) Glucagon
b) Epinephrine
c) Cortisol
d) Insulin

16) Which of the following statement is true?
a) Glycolysis occurs only in mammalian cells
b) Glycolysis occurs in mitochondria
c) Glycolysis occurs in the presence and absence of oxygen
d) Glycolysis occurs when ATP concentration is high.

17) What is the rate-limiting step in glycolysis?
a) Hexokinase
b) Phosphohexose isomerase
c) Glyceraldehyde-3-phosphate dehydrogenase
d) Enolase

18) The net gain of ATP during the conversion of glucose to pyruvate is:
a) 1 ATP
b) 2 ATP
c) 1 ATP +1 GTP
d) 4 ATP

19) During the conversion of glucose to pyruvate, two NADH molecules are generated. Which of the following steps generates NADH?
a) Conversion of fructose-6-phosphate to fructose-1-6-bisphosphate
b) Conversion of glyceraldehydes-3-phosphate to 1-3-bisphosphoglycerate
c)Conversion of 3-phosphoglycerate to 2-phosphoglycerate
d) Conversion of phosphoenolpyruvate to pyruvate

20) What is the committed step in glycolysis?
a) Conversion of glucose to glucose-6-phosphate
b) Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
c) Conversion of glyceraldehydes-3-phosphate to 1-3-bisphosphoglycerate
d) Conversion of 3-phosphoglycerate to 2-phosphoglycerate

21) Glycolysis consists of three irreversible steps. Which of the following enzyme catalyzed reaction are not irreversible steps in glycolysis?
a) Hexokinase
b) Phosphofructokinase
c) Glyceraldehyde-3-phosphate kinase
d) Pyruvate kinase

22) The following are the negative regulators of phosphofructokinase except
a) ATP
b) AMP
c) Citrate
d) pH

23) Which of the following step is inhibited by sodium fluoride?
a) Glyceraldehyde-3-phosphate dehydrogenase
b) 3-phosphoglycerate mutase
c) Enolase
b) AMP

24) Which of the following step is inhibited during arsenate poisoning?
a) Glyceraldehyde-3-phosphate dehydrogenase
b) 3-phosphoglycerate mutase
c) Enolase
d) Pyruvate kinase

25)Which of the following enzyme catalyzes the conversion of pyruvate to lactate?
a) Pyruvate reductase
b) Lactate reductase
c) Lactate dehydrogenase
d) Pyruvate dehydrogenase

26) Glucokinase is an isoenzyme of hexokinase that has high Km and Vmax. Which of the following organ expresses glucokinase?
a) Kidney
b) Muscle
c) Liver
d) Brain

27) Gluconeogenesis is the production of glucose from non-carbohydrate molecules. Which of the following is not substrate for gluconeogenesis?
a) Lactate
b) Alanine
c) Glycerol
d) Acetyl CoA

28) Gluconeogenesis occurs in liver and kidney. Which is of the following enzyme are important for gluconeogenesis are expressed exclusively in these tissues?
a) Glucose-6-phosphatase
b) Fructose-1,6-Bisphosphatase
c) Phosphoenolpyruvate carboxykinase
d) Pyruvate carboxylase

29) During gluconeogenesis, the three irreversible steps of glycolysis have to be bypassed. The first step is the conversion of pyruvate to phosphoenolpyruvate. Which of the following statement is false regarding the reaction step?
a) This reaction involves two-step process catalyzed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase
b) Conversion of oxaloacetate from pyruvate occurs in mitochondria and shuttled into the cytosol.
c) Formation of phosphoenolpyruvate requires both ATP and GTP as an energy source.
d) Acetyl CoA is an activator of enzyme pyruvate carboxylase.

30) During gluconeogenesis, the three irreversible steps of glycolysis have to be bypassed. The final step is the conversion of glucose-6-P to glucose that is catalyzed by glucose-6-phosphatase. Which of the following statement is true about the reaction step?
a) Conversion of glucose-6-phosphate to glucose releases one ATP molecule
b) It is a highly active enzyme in skeletal muscle
c) The defect in glucose-6-phosphatase leads to abnormal accumulation of glycogen in the liver
d) The reaction occurs in mitochondria

31) Which of the following statement is true about the Cori Cycle?
a) The Cori cycle involves three tissues muscle, liver and brain
b) It involves transport of lactate from the liver to skeletal tissue for gluconeogenesis
c) It involves transport of lactate from skeletal muscle to liver for gluconeogenesis
d) It is active during resting stages and well-fed condition

32) During prolonged starvation, which of the following hormone is responsible for increasing gluconeogenesis in the liver?
a) Insulin
b) Glucagon
c) TSH
d) Thyroxine

Multiple Choice Answer Review
1-d) UDP-Galactose 4- epimerase
2-c) Galactose-1-Phosphate Uridyl transferase
3- d) Fructose-2,6-Bisphosphate
4-b)Phosphofructokinase
5-d) Pyruvate Kinase
6-d) Pyruvate Kinase M2
7-d) GLUT4
8-b) GLUT2
9-c) GLUT5
10-d) Alanine
11-d) during lactate formation, NADH is reconverted into NAD
12-b) Glucokinase
13-d) PFK-1 is regulated by posttranslational modification such as phosphorylation
14-b) Activated protein kinase A phosphorylates PFK-2 and activates phosphatase domain
15-d) Insulin
16-c) Glycolysis occurs in the presence and absence of oxygen
17-a) Hexokinase
18-b) 2 ATP
19-b) Conversion of glyceraldehydes-3-phosphate to 1-3-bisphosphoglycerate
20-b) Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
21-c) Glyceraldehyde-3-phosphate kinase
22-b) AMP
23-c) Enolase
24-a) Glyceraldehyde-3-phosphate dehydrogenase
25-c) Lactate dehydrogenase
26-c) Liver
27-d) Acetyl CoA
28-a) Glucose-6-phosphatase
29-d) Acetyl CoA is an activator of enzyme pyruvate carboxylase
30-c) Defect in glucose-6-phosphatase leads to abnormal accumulation of glycogen in liver
31-c) It involves transport of lactate from skeletal muscle to liver for gluconeogenesis
31-b) Glucagon

Carbohydrate Metabolism: MCQ on Glycolysis &Gluconeogenesis Carbohydrate Metabolism: MCQ on Glycolysis &Gluconeogenesis Reviewed by Biotechnology on October 28, 2017 Rating: 5

Lipid Metabolism: MCQs

October 28, 2017
Multiple Choice Question on Lipid Metabolism

1) The following require cholesterol EXCEPT
a) Bile acid synthesis
b) Steroid hormone synthesis
c) Membrane fluidity
d) Thyroid hormone synthesis

2) Which of the following lipid act as lungs surfactant?
a) Phosphatidylcholine
b) Phosphatidylethanolamine
c) Ceramide
d) Phosphatidylinositol

3) Which of the following is simple lipid?
a) Lecithin
b) Fatty acid
c) Triacylglycerol
d) Steroids

4) All of the following is complex lipids, except
a) Phosphatidic acid
b) Cerebroside
c) Cardiolipin
d) Cholesterol

5) Which of the following is essential fatty acid?
a) Linolenic acid
b) Arachidonic acid
c) Oleic acid
d) Palmitic acid

6) Bile acid is derived from:
a) Cholesterol
b) Amino acids
c) Fatty acids
d) Bilirubin

7) Which of the following lipid is mostly present in mitochondrial membranes?
a) Lecithin
b) Cephalin
c) Cardiolipin
d) Ceramide

8) Insulin enhances the uptake of triacylglycerols in adipose tissues. Which of the following enzyme is activated that facilitates the uptake?
a) Hormone-sensitive lipase
b) Lipoprotein lipase
c) LCAT
d) Apo C-II

9) Familial hypercholesterolemia is a genetic disorder of lipid metabolism. The defect lies in
a) Transport of cholesterol from extrahepatic tissue to the liver
b) Impairment of cholesterol degradative pathway
c) Impairment of uptake of cholesterol by tissues
d) Impairment of HDL metabolism due to deficiency of Apo-A

10) Which of the following inhibits acetyl CoA carboxylase- a rate-limiting enzyme of fatty metabolism?
a) Citrate
b) ATP
c) Malonyl CoA
d) Acyl CoA

Multiple Choice Answer Review
1-d) Thyroid hormone synthesis
2-a) Phosphatidyl choline
3-c) Triacylglycerol
4-d) Cholesterol
5-a) Linolenic acid
6-a) Cholesterol
7-c) Cardiolipin
8- b) Lipoprotein lipase
9-c) Impairment of uptake of cholesterol by tissue
10­-d) Acyl CoA



Lipid Metabolism: MCQs Lipid Metabolism: MCQs Reviewed by Biotechnology on October 28, 2017 Rating: 5

Lipid Metabolism: MCQ on Lipid Digestion and Absorption

October 28, 2017
Multiple Choice Question on Lipid Digestion and Absorption

1) What is the enzyme responsible for the breakdown of triglycerides into fatty acids and monoacylglycerol in the intestine?
a) Pancreatic lipase
b) Lipoprotein lipase
c) Hormone-sensitive lipase
d) Phospholipase

2) What is the function of bile salt in the intestine?
a) Activator of lipase
b) Emulsifier
c) Co-factor for cholesteryl esterase
d) Inhibitor of lipid absorption

3) What is the precursor for bile salt synthesis?
a) Fatty acid
b) Glucose
c) Cholesterol
d) Glycerol

4) The anti-obesity drug Orlistat inhibits
a) Pancreatic lipase
b) Lipoprotein lipase
c) Hormone-sensitive lipase
d) Phospholipase
5) Which of the following class of fatty acids can be directly absorbed from intestine?
a) Very long chain fatty acid
b) Long-chain fatty acid
c) Short-chain fatty acid
d) Cholesterol esters

6) The lipid digestion process is regulated by different local hormones. The cholecystokinin hormone released from
a) Mucosa of jejunum
b) Pancreatic delta cells
c) Gastric Parietal cells
d) Pancreatic alpha cells

7) Which of the following is not the effect of cholecystokinin released from mucosal cells of jejunum?
a) Contraction of gall bladder and release of bile acids
b) The release of digestive enzymes from the exocrine pancreas
c) The slower release of gastric content into the stomach
d) Increased of gastric motility

8) Lack of appropriate lipid absorption leads to a condition known as
a) Metabolic syndrome
b) Obesity
c) Fatty liver
d) Steatorrhea

Multiple Choice Question Answers
1-c) Hormone-sensitive lipase
2-b) Emulsifier
3-c) Cholesterol
4-c) Hormone-sensitive lipase
5-c) Short-chain fatty acid
6-a) Mucosa of the jejunum
7-c) Slower release of gastric content into the stomach
8-d) Steatorrhea
Lipid Metabolism: MCQ on Lipid Digestion and Absorption Lipid Metabolism: MCQ on Lipid Digestion and Absorption Reviewed by Biotechnology on October 28, 2017 Rating: 5

Metabolism: Tricarboxylic Acid or TCA Cycle MCQ

October 28, 2017
Multiple Choice Question on Tricarboxylic Acid or TCA Cycle

1) The conversion of pyruvate to acetyl CoA is catalyzed by enzyme pyruvate dehydrogenase. In this reaction
a) NADPH is oxidized to NADP
b) NADH is oxidized to NAD
c) NADP is reduced to NADPH
d) NAD is reduced to NADH

2) The conversion of pyruvate to acetyl CoA is known as
a) Oxidative decarboxylation
b) Oxidative phosphorylation
c) Reductive biosynthesis
d) Reductive decarboxylation

3) Which of the following is false regarding enzyme pyruvate dehydrogenase?
a) It is multi-enzyme complex
b) It catalyzes the reversible reaction (conversion of pyruvate to acetyl CoA)
c) The pyruvate dehydrogenase complex is a mitochondrial enzyme
d) It requires thiamine, flavin and nicotine vitamin co-enzymes

4) Which of the following is not the regulator of pyruvate dehydrogenase?
a) Calcium
b) Acetyl CoA
c) ATP
d) Citrate

5) Arsenic binds to the thiol group of lipoic acid and interferes the activity of enzymes that require lipoic acid as co-factor. Which of the following enzyme does not require lipoic acid?
a) Pyruvate dehydrogenase
b) Isocitrate dehydrogenase
c) Malate dehydrogenase
d) Branched-chain amino acid dehydrogenase

6) Citrate synthase is the enzyme that catalyzes the condensation of acetyl CoA and oxaloacetate to citrate. Which of the following is an activator of this enzyme?
a) Succinyl CoA
b) NADH
c) Fatty Acyl CoA
d) ADP

7) Which of the following enzyme catalyzes substrate level phosphorylation i.e conversion of GDP to GTP?
a) Malate dehydrogenase
b) Fumarase
c) Isocitrate dehydrogenase
d) Succinyl CoA thiokinase

8) When two carbon Acetyl CoA is oxidized to CO2, the total yield of ATP is
a) 8
b) 12
c) 14
d) 16

9) Which of the following is not the irreversible reaction of the Krebs cycle?
a) Isocitrate dehydrogenase
b) Alpha-ketoglutarate dehydrogenase
c) Citrate synthase
d) Malate dehydrogenase

10) Which of the following enzyme causes congenital lactic acidosis
a) Isocitrate dehydrogenase
b) Alpha-ketoglutarate dehydrogenase
c) Pyruvate dehydrogenase
d) Malate dehydrogenase

Multiple Choice Answers
1- d) NAD is reduced to NADH
2- a) Oxidative decarboxylation
3-b) It catalyzes the reversible reaction (conversion of pyruvate to acetyl CoA)
4-d) Citrate
5-c) Malate dehydrogenase
6-d) ADP
7-d) Succinyl CoA thiokinase
8-b) 12
9-d) Malate dehydrogenase
10-c) Pyruvate dehydrogenase



Metabolism: Tricarboxylic Acid or TCA Cycle MCQ Metabolism: Tricarboxylic Acid or TCA  Cycle MCQ Reviewed by Biotechnology on October 28, 2017 Rating: 5

Metabolism of Red Blood Cells: MQC

October 28, 2017
Which of the following is FALSE about the fate of the glycolytic pathway in erythrocytes?
a) Glycolysis is the sole source of ATP in erythrocytes.
b) Deficiency of pyruvate kinase leads to hemolytic anemia.
c) Pyruvate generated during glycolysis is converted to lactate.
d) Pyruvate generated during glycolysis is converted to acetyl CoA and enters the TCA cycle in mitochondria.


The objective of the MCQ above is to discuss
- Red blood cells shape and morphology
- The fate of glucose in red blood cells
- Metabolic control of glucose metabolism

Red blood cells are bone marrow-derived non-dividing cells that contain hemoglobin (95% of intracellular protein) and help to transport oxygen from lungs to peripheral tissue. The RBCs help in disposal of carbon dioxide and a proton from the peripheral tissue. The red blood cells are a biconcave structure that increases the surface-to-volume ratio and facilitate gas exchange. Morphologically, red blood cells are anucleated and lack organelles such as mitochondria, lysosomes or Golgi apparatus. Although biosynthetic pathways do not occur in RBC, the ATP, and NADPH are required for maintenance of cellular structure The energy is utilized by anion-exchange proteins, NA+ K+ ATPase, other transporter proteins to maintain cellular homeostasis. The glycolytic pathway occurs in cytosol and pyruvate can be converted to lactate and regenerate NAD required for continuation of the glycolytic pathway. These characteristics of the glycolytic pathway make glucose suitable source of energy in red blood cells.

In red blood cells, glucose can into two different pathway i.e glycolysis and pentose phosphate pathway. Glycolysis is the conversion of glucose into pyruvate with the generation of net 2 ATPs and 2 NADH. The glycolytic pathway is activated when cellular ATP level is decreased. These ATPs are utilized by various ion transporter to maintain the integrity of the cells. The hemoglobin in red blood cells bind to oxygen and deliver to the target tissues. Auto-oxidation of iron-containing hemoglobin and propagation of electrons lead to a generation of free radicals that are toxic to the tissues. The red blood cell consists of enzymes such as catalase, superoxide dismutase. Superoxide dismutase, glutathione requiring enzyme, converts superoxide to hydrogen peroxide and catalase converts hydrogen peroxide into water and oxygen. Superoxide dismutase enzyme activity depends on the availability of reduced glutathione. The glutathione peroxidase catalyzes the cycling of reduced glutathione in an expense of NADPH. The pentose phosphate pathway generates NADPH that is utilized by RBC for converting toxic superoxide radicals to non-toxic oxygen and water.



The fate of glucose in red blood cells



Glutathione NADPH cycle in RBC.
SOD- Superoxide dismutase, GSH- Glutathione, GPX-Glutathione peroxidase, G6PD-Glucose-6-phosphate dehydrogenase, CAT- Catalase

The defective enzymes of the glycolytic pathway or pentose phosphate pathway can adversely affect the cellular integrity of red blood cells by two distinct mechanisms. The defect in the glycolytic pathway can lead to decreased ATP production, decrease the activity of ATP dependent ions channels, dysregulation of ions and cellular lysis. On the other hand, the defect in the enzyme of pentose phosphate pathway (e.g. glucose-6-phosphate dehydrogenase) lead to decreased NADPH, decreased the activity of NADPH dependent enzymes, accumulation of toxic free radicals ultimately leading to hemolytic anemia.

Correct: Answer D ( Red blood cells lack mitochondrial require for conversion of pyruvate to acetyl CoA)

Metabolism of Red Blood Cells: MQC Metabolism of Red Blood Cells: MQC Reviewed by Biotechnology on October 28, 2017 Rating: 5

Non-Esterified Fatty Acid in Plasma- MCQ of the Day

October 24, 2017
Question
 Non-esterified fatty acids in the plasma
a) circulate in an unbound state
b) bind to lipoproteins and circulated
c) bind to albumin and circulated
d) bind to the fatty acid binding protein and circulated
Objective:
The objective of the above question is to discuss
-) the function of non-esterified fatty acid and derivatives
-) the metabolism of non-esterified fatty acids.
-) the origin of non-esterified fatty acid in plasma
-) role of non-esterified fatty acid in diabetes

Answer and Explanation
Fatty acids play critical roles in the energy metabolism of in mammals. The bulk of fatty acids are stored in adipose tissues as triglycerides and mobilized during the energy-deprived state to tissues such as skeletal muscle, heart to fulfill their energy requirements. In addition, they are building blocks for phospholipids and other complex lipids which are a component of the cell membrane, a precursor for biologically active substances such as leukotrienes, prostaglandins, etc. and; insulation for nerve tissues.

Triglycerides are a major dietary source of fatty acids which are absorbed in the small intestine. The absorbed triglycerides are incorporated into chylomicrons. Chylomicrons are the lipoproteins that are formed in intestinal cells and once triglycerides are loaded into it to form mature chylomicrons, they are transported via lymphatics to peripheral tissues. The triglycerides are predominantly taken up by adipose tissue.

The endothelial lipoprotein lipase hydrolyzes triglycerides into non-esterified fatty acids (NEFA) and glycerol, and facilitate uptake by adipose tissues. These NEFAs enters the adipose tissues re-esterified into adipose tissues. Minimum quantity of NEFAs escape into the bloodstream; reaches hepatocytes where they are taken up, re-esterified into triglycerides, incorporated into very low-density lipoproteins.

NEFAs exist in a low concentration in plasma and interstitial fluids. Because of the low solubility of non-esterified fatty acids in aqueous solutions, they require binding and transport protein in extracellular fluids. The fatty acids are bound asymmetrically to hydrophobic pockets of the albumin. Plasma albumin possesses multiple binding sites NEFAs with moderate to high affinity for them. The amphipathic nature of fatty acids facilitates binding to albumin by both hydrophobic and electrostatic interactions. Albumin-FA interaction also facilitates the efficient uptake of fatty acids by target tissues such as cardiomyocytes.

Diabetes mellitus, NEFAs, and Albumin
Increased NEFAs has been associated with insulin resistance and microvascular complications in diabetes. Increased blood glucose in diabetes mellitus has shown to modify proteins such as hemoglobin and albumin. The non-enzymatic glycation of these proteins leads to altered function and formation of advanced glycation end products that elicit an inflammatory response and microvascular derangements. Recently, a study was conducted to investigate whether the glycation or glycoxidation of albumin is relevant to NEFA related pathobiology. The investigator hypothesized that modification of albumin due to hyperglycemia potentially result in an impaired binding to NEFAs. As predicted, the modification of albumin invitro reduced binding to NEFAs to albumin. These changes were similar to those observed in diabetic individuals where they have high NEFAs, and the binding affinity toward albumin is reduced. The result showed that hyperglycemia leads to glycation and oxidation of albumin, reduced binding affinity. These event lead promote platelets activation and aggregation. The impaired ability to sequester platelet-derived NEFAs namely arachidonic acid may account for these effects. Thus, increased NEFAs and increased glycation of albumin may provide a proatherogenic environment characterized in diabetes.


Correct Answer is C




Non-Esterified Fatty Acid in Plasma- MCQ of the Day Non-Esterified Fatty Acid in Plasma- MCQ of the Day Reviewed by Biotechnology on October 24, 2017 Rating: 5

HYPOGLYCEMIA: Clinical Presentation and Biochemical Diagnosis

October 23, 2017
A 54- year old female was brought to the Emergency Department with complaints of sweating, palpitations, and dizziness. Her random blood glucose is 25 mg/dl. After infusion of glucose, the symptoms were relieved. Upon clinical chemistry analysis, her plasma insulin level was higher with low level of C-peptide.

Provisional Diagnosis: Hypoglycemia, due to hyperinsulinemia

Answer and Explanation
First, the case presentation suggests that the female subject may have been suffering from hypoglycemia based on a classical feature of Whipple Triad which includes: 
a) the decreased blood glucose level below normal reference level ( 60-110 mg/dL), 
b) the subject is also presented with classical symptoms of hypoglycemia such as sweating, palpitation, and dizziness.
c) the symptoms were immediately relieved with the infusion of glucose.


Second, the blood chemistry analysis revealed the insulin level in the subject was higher. The higher blood insulin level is responsible for decreased blood glucose. Insulin is a 51 amino-acid peptide hormone produced by islet beta cells of the pancreas and has a critical role in maintaining normal blood glucose level (60-110 mg/dL). In healthy individuals, the rise in postprandial blood glucose ( spike of blood glucose after a meal) results in an increased flux of glucose into islet beta cells of the pancreas. The islet beta cell expresses GLUT2 glucose transporter have high Vmax and high Km that enable efficient transport of glucose into beta cells when the blood glucose level rise above its normal physiological level. The intracellular glucose is now rapidly phosphorylated to form glucose-6-phosphate by an enzyme glucokinase and subsequently, enters the glycolytic pathway to generate ATP. In response to high ATP/ADP ratio, the ATP-sensitive potassium channel is closed, resulting in depolarization and influx of calcium into cells, resulting in a release of insulin granules into the blood. The insulin binds to insulin receptor multiple target tissues including liver and muscles. Insulin decreases blood glucose level up-regulating glucose intake, glycogen synthesis, and conversion into triglycerides and storage. Insulin also downregulates glycogen breakdown, gluconeogenesis, and release of glucose into the blood. When insulin level is higher than normal physiological level, the equilibrium shift towards increased storage and decrease utilizing of glucose resulting in hypoglycemia.



Figure 1: Mechanism of Insulin Release






Figure 2: Structure of Insulin consisting of two chains connected by disulfide bonds. C-peptide is cleaved during post-translation modification resulting in an equimolar concentration of insulin and C-peptide in insulin-secreting granules of beta cells. The A chain and B chain consist of 21 and 30 amino acids respectively.


Finally, the hypoglycemia is the effect of hyperinsulinemia and insulinemia may be associated with tumors associated with hyper-insulin secretion or exogenous infusion of insulin in cases of insulin-requiring diabetes. The measurement of C-peptide enables differentiation of endogenous or infused insulin. C-peptide is a C-terminal part of proinsulin which is cleaved off during post-translational modification and maturation of active insulin. C-peptide is present in an equimolar concentration in the insulin granules and they are co-secreted with insulin from the beta cell of the pancreas. The C-peptide has a longer half-life than insulin and therefore it is a sensitive biomarker to monitor the function of the beta cell of the pancreas. The disproportionate levels of insulin and C-peptide suggest that the most likely cause of hypoglycemia is associated with insulin overdose. In the case of a tumor of the beta cell, a proportionate increase in insulin and C-peptide is anticipated.
HYPOGLYCEMIA: Clinical Presentation and Biochemical Diagnosis HYPOGLYCEMIA: Clinical Presentation and Biochemical Diagnosis Reviewed by Biotechnology on October 23, 2017 Rating: 5
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