- A – Wrong. Glucagon is not an enzyme, but a peptide hormone that raises blood glucose levels by glycogenolysis, and stimulates gluconeogenesis and ketogenesis. The main target tissues are the liver.
- B – Wrong. Glucose-6-phosphate dehydrogenase is an enzyme that begins the breakdown of glucose by the pentose phosphate cycle.
- C – Wrong. Glucokinase is a liver enzyme that phosphorylates glucose in the hepatocyte cytoplasm to glucose-6-phosphate. Its activity is greatly affected by glucose levels.
- D – Wrong. Hexokinase is an enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate in extrahepatic tissues. Hexokinase activity for a very low Km value is not affected by blood glucose concentration.
- E – Correct answer. Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to provide free glucose. It is present in the liver and kidneys. Missing (!) In muscle and adipose tissue. Its presence allows the supply of glucose from the tissues to the bloodstream.
Question 2.
- A – Wrong. Alanine can be metabolized to pyruvate by alanine aminotransferase catalysis, which then involves the formation of oxaloacetate with the participation of pyruvate carboxylase, Mg 2+, ATP and CO 2, and malate after reduction (everything takes place in mitochondria). This crosses the mitochondrial membrane (it is impermeable to oxaloacetate), it is again oxidized in the cytoplasm to oxaloacetate and it changes to phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase, GTP and CO 2.
- B – Wrong. Although pyruvate cannot be converted directly to phosphoenolpyruvate (pyruvate kinase can only work in one direction for thermodynamic reasons), phosphoenolpyruvate is formed again in the gluconeogenetic pathway via pyruvate carboxylase and phosphoenolpyruvate carboxykinases via oxaloacetate, malate and oxaloacetate again.
- C – Wrong. Lactate after dehydrogenation by lactate dehydrogenase gives pyruvate, which can be converted to phosphoenolpyruvate by "detonation", ie by gluconeogenesis enzymes (pyruvate carboxylase, phosphoenolpyruvate carboxykinase).
- D – Right. Palmitate undergoes β-oxidation and produces 8 acetyl-CoA, which in mitochondria can be further oxidized in the citrate cycle to CO 2 and H 2 O already in the first stages of the cycle, so there are not too many carbon residues converted to sufficient oxaloacetate needed for gluconeogenesis. Indeed, if oxaloacetate is removed from the cycle and not replaced, the cell's ability to produce much-needed ATP would be limited. Thus, acetyl-CoA is not a suitable substrate for gluconeogenesis; this is pyruvate formed from amino acids (alanine), which provides sufficient oxaloacetate by the reaction catalyzed by pyruvate carboxylase. Thus, gluconeogenesis does not interfere with metabolism in the citric acid cycle.
- E – Wrong. Oxaloacetate is an important substrate for gluconeogenesis. It is formed from pyruvate by the action of pyruvate carboxylase. However, it is impermeable across the mitochondrial membrane, so it must be converted to malate, which is permeable; in the cytoplasm, it is again dehydrogenated to oxaloacetate, which gives phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase; it provides glucose in the gluconeogenetic pathway via triose phosphates and hexose phosphates.
Question 3.
- A – Wrong. In contrast, insulin stimulates hepatic glucokinase activity and phosphorylates intracellular glucose to glucose-6-phosphate. This lowers the intracellular glucose level and thus indirectly promotes the flow of glucose from the circulation to the hepatocyte. Insulin promotes hepatic glycolysis. In contrast, it inhibits the activity of hepatic glucose-6-phosphatase, which releases glucose from the liver.
- B – Correct. Insulin promotes glucose utilization in muscle by promoting translocation of glucose through the circulatory system into the cell, further stimulating the production of glucose-6-phosphate, which can be isomerized to glucose-1-phosphate, a precursor for glycogen synthesis.
- C – Wrong. Insulin has the opposite effect, stimulates lipogenesis and is a very effective inhibitor of lipolysis.
- D – Wrong. Insulin, in turn, has the effect of promoting glycogen synthesis from glucose.
- E – Wrong. Insulin, on the other hand, stimulates the entry of amino acids into cells, and stimulates protein synthesis (anabolic effect).
Question 4.
- A – Correct. The role of the Cori cycle (also the lactic acid cycle) is to transfer excess reducing equivalents from the muscles to the liver. In fast-moving muscles (during contraction), the supply of O 2 mitochondria is not fast enough to reoxidize the NADH formed during glycolysis. As the concentration of cytoplasmic NADH increases, lactate dehydrogenase catalyzes the transfer of reducing equivalents from NADH to pyruvate to form lactate. This penetrates from the muscles into the circulation and is taken up by the liver. In them, lactate dehydrogenase transfers electrons back to NAD to form pyruvate. In the gluconeogenetic pathway, pyruvate is converted into glucose, which leaves the liver and enters the muscles from the circulation. This cycle allows the skeletal muscles to work for a short time in anaerobic conditions.
- B – Wrong. Glucose-6-phosphate dehydrogenase is the initial enzyme that initiates the pentose phosphate pathway of glucose metabolism.
- C – Wrong. Pyruvate dehydrogenase converts pyruvate to acetyl CoA, which enters the citric acid cycle. Before that, pyruvate cytoplasm must be transferred to the mitochondria. There, pyruvate undergoes oxidative decarboxylation catalyzed by a multienzyme complex, collectively called the pyruvate dehydrogenase complex.
- D – Wrong. Glucokinase catalyzes the phosphorylation of glucose in the liver to glucose-6-phosphate and thus initiates the glycolytic pathway.
- E – Wrong. Hydroxymethylglutaryl-CoA reductase is a key enzyme in cholesterol synthesis.
Question 5.
- A – decreases
- B – rising
- C – decreases
- D – rising
- E – decreases
Question 6.
- C – Correct. By binding to the surface membrane receptor, glucagon activates the adenylate cyclase system and thus increases the cAMP content in the cell (cAMP acts as a "second messenger"), thereby allosterically activating cAMP-dependent protein kinase, which converts phosphorylase b to active phosphorylase a, which cleaves glycogen in the liver (glycogenolytic effect of glucagon in the liver; not in muscle). Glycogen synthesis is inactivated (inactivated by protein phosphatase 1). After ingestion of food, glucose enters the vena portae, glucosemia rises; reaches its maximum in 30-60 minutes. In a healthy individual, the value does not exceed 10 mmol / l (usually 7-8 mmol / l).
Question 7.
- A – Correct. Absolute or relative lack of insulin prevents the transport of glucose across the cell membrane (excluding hepatocyte), reduces the activation of hexokinase and thus its phosphorylation to glucose-6-phosphate.
- B – Wrong. The site of gluconeogenesis is mainly the liver, not the muscles.
- C – Correct. Hepatic gluconeogenesis is significantly involved in hyperglycemia in diabetes. The main substrate of gluconeogenesis is amino acids (alanine), which are converted to pyruvate and by the gluconeogenetic pathway to glucose. The reaction requires energy, which is taken from the oxidation of fatty acids (lipolysis). Increased acetyl CoA production (β-oxidation of fatty acids) allosterically activates pyruvate carboxylase (an enzyme that initiates the conversion of pyruvate to phosphoenolpyruvate) and, conversely, inhibits pyruvate dehydrogenase, which is required for pyruvate (or acetyl CoA) to enter the citric acid cycle. Increased concentrations of alanine and fatty acids inhibit the conversion of phosphoenolpyruvate to pyruvate, thereby inhibiting glycolysis and promoting gluconeogenesis.
- D – Wrong. Glucose transfer to the hepatocyte is not insulin-dependent. In other cells, this glucose carrier protein facilitates the translocation of glucose across the membrane and requires insulin. Indirectly, however, insulin deficiency affects the entry of circulating glucose into the hepatocyte in diabetes by insufficiently activated glucokinase, which normally increases the gradient between "free" glucose outside and inside the liver cell.
- E – Wrong. An increase in the renal threshold for glucose occurs later in the course of diabetes and is a consequence of hyperglycemia rather than its primary cause. However, an increased renal threshold in advanced diabetes may contribute to the discrepancy finding of high hyperglycemia with relatively low glycosuria.
- F – Correct. In insulin deficiency, the effect of glucagon, which promotes hyperglycemia by increased hepatic glycogenolysis and stimulation of gluconeogenesis, predominates.
- G – Wrong. Insulin deficiency, on the other hand (due to relative glucagon excess), promotes lipolysis, which is needed as an energy source for gluconeogenesis.
Question 8.
- A – Wrong. This is not a reduced breakdown, but increased production of ketone bodies in the liver.
- B – Correct. The combination of insulin deficiency (or its effect) with the increased action of glucagon leads to insufficient glucose utilization, gluconeogenesis and stimulation of lipolysis (enhancement of β-oxidation of fatty acids and overproduction of acetyl CoA in the liver).
- C – Wrong. The non-enzymatic conversion of acetoacetate to acetone, on the other hand, induces the possibility of ketone bodies also excreted by the lungs (smell of fruit in the breath).
- D – Right. Increased fatty acid catabolism in the liver, which arrives here from lipolysis from fat depots, leads to overproduction of acetyl CoA, which cannot be degraded in the citric acid cycle (lack of oxaloacetate formed during glycolysis); from the acetyl-CoA molecule is condensed to acetoacetyl-CoA, from which acetoacetate is formed; in the absence of O2, it can be reduced to hydroxybutyrate. Both carboxylic acids are moderately strong (pK around 4) and significantly affect blood pH in terms of acidemia.
- E – Correct. Increased production of acetyl-CoA in the liver, leads to the accumulation of condensation product - acetoacetate. Thus, it is an overproduction of ketone bodies in the liver, not a reduced degradation.
- F – Correct. The formation of hydroxymethylglutaryl-CoA (HMG-CoA) is one of the pathways from which acetoacetate is formed. Acetoacetyl-CoA takes up another molecule of acetyl CoA; this produces HMG-CoA, which cleaves acetyl-CoA by HMG-CoA lyase and remains "free" acetoacetate. This method of acetoacetate formation from aceto-acetyl-CoA appears to be more important than simple deacylation.
Question 9.
- A – Correct. Persistent severe hyperglycemia in noninsulin-dependent diabetes induces osmotic diuresis. In times of insufficient water supply, especially in the elderly after a stroke or infection, ECT hyperosmolarity occurs. Residual insulin secretion is sufficient to prevent excessive ketogenesis, but it is not sufficient to affect hyperglycemia. Hyperosmolar coma, therefore, occurs more frequently in noninsulin-independent diabetes; has a high mortality (up to 50%).
- B – Wrong. Lack of insulin combined with excess glucagon is the cause of ketoacidotic coma in IDDM. In NIDDM, residual insulin secretion prevents increased production of ketone bodies but does not prevent hyperglycemia.
- C – Wrong. Insulin does not affect the utilization of glucose by the brain.
- D – Wrong. Glycation of collagen in the basement membrane of glomeruli does cause increased permeability, which first leads to an increase in albuminuria as the first laboratory sign of incipient diabetic nephropathy; however, it does not cause osmotic diuresis.
- A – Wrong. Glucagon is not an enzyme, but a peptide hormone that raises blood glucose levels by glycogenolysis, and stimulates gluconeogenesis and ketogenesis. The main target tissues are the liver.
- B – Wrong. Glucose-6-phosphate dehydrogenase is an enzyme that begins the breakdown of glucose by the pentose phosphate cycle.
- C – Wrong. Glucokinase is a liver enzyme that phosphorylates glucose in the hepatocyte cytoplasm to glucose-6-phosphate. Its activity is greatly affected by glucose levels.
- D – Wrong. Hexokinase is an enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate in extrahepatic tissues. Hexokinase activity for a very low Km value is not affected by blood glucose concentration.
- E – Correct answer. Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to provide free glucose. It is present in the liver and kidneys. Missing (!) In muscle and adipose tissue. Its presence allows the supply of glucose from the tissues to the bloodstream.
Question 2.
- A – Wrong. Alanine can be metabolized to pyruvate by alanine aminotransferase catalysis, which then involves the formation of oxaloacetate with the participation of pyruvate carboxylase, Mg 2+, ATP and CO 2, and malate after reduction (everything takes place in mitochondria). This crosses the mitochondrial membrane (it is impermeable to oxaloacetate), it is again oxidized in the cytoplasm to oxaloacetate and it changes to phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase, GTP and CO 2.
- B – Wrong. Although pyruvate cannot be converted directly to phosphoenolpyruvate (pyruvate kinase can only work in one direction for thermodynamic reasons), phosphoenolpyruvate is formed again in the gluconeogenetic pathway via pyruvate carboxylase and phosphoenolpyruvate carboxykinases via oxaloacetate, malate and oxaloacetate again.
- C – Wrong. Lactate after dehydrogenation by lactate dehydrogenase gives pyruvate, which can be converted to phosphoenolpyruvate by "detonation", ie by gluconeogenesis enzymes (pyruvate carboxylase, phosphoenolpyruvate carboxykinase).
- D – Right. Palmitate undergoes β-oxidation and produces 8 acetyl-CoA, which in mitochondria can be further oxidized in the citrate cycle to CO 2 and H 2 O already in the first stages of the cycle, so there are not too many carbon residues converted to sufficient oxaloacetate needed for gluconeogenesis. Indeed, if oxaloacetate is removed from the cycle and not replaced, the cell's ability to produce much-needed ATP would be limited. Thus, acetyl-CoA is not a suitable substrate for gluconeogenesis; this is pyruvate formed from amino acids (alanine), which provides sufficient oxaloacetate by the reaction catalyzed by pyruvate carboxylase. Thus, gluconeogenesis does not interfere with metabolism in the citric acid cycle.
- E – Wrong. Oxaloacetate is an important substrate for gluconeogenesis. It is formed from pyruvate by the action of pyruvate carboxylase. However, it is impermeable across the mitochondrial membrane, so it must be converted to malate, which is permeable; in the cytoplasm, it is again dehydrogenated to oxaloacetate, which gives phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase; it provides glucose in the gluconeogenetic pathway via triose phosphates and hexose phosphates.
Question 3.
- A – Wrong. In contrast, insulin stimulates hepatic glucokinase activity and phosphorylates intracellular glucose to glucose-6-phosphate. This lowers the intracellular glucose level and thus indirectly promotes the flow of glucose from the circulation to the hepatocyte. Insulin promotes hepatic glycolysis. In contrast, it inhibits the activity of hepatic glucose-6-phosphatase, which releases glucose from the liver.
- B – Correct. Insulin promotes glucose utilization in muscle by promoting translocation of glucose through the circulatory system into the cell, further stimulating the production of glucose-6-phosphate, which can be isomerized to glucose-1-phosphate, a precursor for glycogen synthesis.
- C – Wrong. Insulin has the opposite effect, stimulates lipogenesis and is a very effective inhibitor of lipolysis.
- D – Wrong. Insulin, in turn, has the effect of promoting glycogen synthesis from glucose.
- E – Wrong. Insulin, on the other hand, stimulates the entry of amino acids into cells, and stimulates protein synthesis (anabolic effect).
Question 4.
- A – Correct. The role of the Cori cycle (also the lactic acid cycle) is to transfer excess reducing equivalents from the muscles to the liver. In fast-moving muscles (during contraction), the supply of O 2 mitochondria is not fast enough to reoxidize the NADH formed during glycolysis. As the concentration of cytoplasmic NADH increases, lactate dehydrogenase catalyzes the transfer of reducing equivalents from NADH to pyruvate to form lactate. This penetrates from the muscles into the circulation and is taken up by the liver. In them, lactate dehydrogenase transfers electrons back to NAD to form pyruvate. In the gluconeogenetic pathway, pyruvate is converted into glucose, which leaves the liver and enters the muscles from the circulation. This cycle allows the skeletal muscles to work for a short time in anaerobic conditions.
- B – Wrong. Glucose-6-phosphate dehydrogenase is the initial enzyme that initiates the pentose phosphate pathway of glucose metabolism.
- C – Wrong. Pyruvate dehydrogenase converts pyruvate to acetyl CoA, which enters the citric acid cycle. Before that, pyruvate cytoplasm must be transferred to the mitochondria. There, pyruvate undergoes oxidative decarboxylation catalyzed by a multienzyme complex, collectively called the pyruvate dehydrogenase complex.
- D – Wrong. Glucokinase catalyzes the phosphorylation of glucose in the liver to glucose-6-phosphate and thus initiates the glycolytic pathway.
- E – Wrong. Hydroxymethylglutaryl-CoA reductase is a key enzyme in cholesterol synthesis.
Question 5.
- A – decreases
- B – rising
- C – decreases
- D – rising
- E – decreases
Questiona 6.
- C – Correct. By binding to the surface membrane receptor, glucagon activates the adenylate cyclase system and thus increases the cAMP content in the cell (cAMP acts as a "second messenger"), thereby allosterically activating cAMP-dependent protein kinase, which converts phosphorylase b to active phosphorylase a, which cleaves glycogen in the liver (glycogenolytic effect of glucagon in the liver; not in muscle). Glycogen synthesis is inactivated (inactivated by protein phosphatase 1). After ingestion of food, glucose enters the vena portae, glucosemia rises; reaches its maximum in 30-60 minutes. In a healthy individual, the value does not exceed 10 mmol / l (usually 7-8 mmol / l).
Question 7.
- A – Correct. Absolute or relative lack of insulin prevents the transport of glucose across the cell membrane (excluding hepatocyte), reduces the activation of hexokinase and thus its phosphorylation to glucose-6-phosphate.
- B – Wrong. The site of gluconeogenesis is mainly the liver, not the muscles.
- C – Correct. Hepatic gluconeogenesis is significantly involved in hyperglycemia in diabetes. The main substrate of gluconeogenesis is amino acids (alanine), which are converted to pyruvate and by the gluconeogenetic pathway to glucose. The reaction requires energy, which is taken from the oxidation of fatty acids (lipolysis). Increased acetyl CoA production (β-oxidation of fatty acids) allosterically activates pyruvate carboxylase (an enzyme that initiates the conversion of pyruvate to phosphoenolpyruvate) and, conversely, inhibits pyruvate dehydrogenase, which is required for pyruvate (or acetyl CoA) to enter the citric acid cycle. Increased concentrations of alanine and fatty acids inhibit the conversion of phosphoenolpyruvate to pyruvate, thereby inhibiting glycolysis and promoting gluconeogenesis.
- D – Wrong. Glucose transfer to the hepatocyte is not insulin-dependent. In other cells, this glucose carrier protein facilitates the translocation of glucose across the membrane and requires insulin. Indirectly, however, insulin deficiency affects the entry of circulating glucose into the hepatocyte in diabetes by insufficiently activated glucokinase, which normally increases the gradient between "free" glucose outside and inside the liver cell.
- E – Wrong. An increase in the renal threshold for glucose occurs later in the course of diabetes and is a consequence of hyperglycemia rather than its primary cause. However, an increased renal threshold in advanced diabetes may contribute to the discrepancy finding of high hyperglycemia with relatively low glycosuria.
- F – Correct. In insulin deficiency, the effect of glucagon, which promotes hyperglycemia by increased hepatic glycogenolysis and stimulation of gluconeogenesis, predominates.
- G – Wrong. Insulin deficiency, on the other hand (due to relative glucagon excess), promotes lipolysis, which is needed as an energy source for gluconeogenesis.
Question 8.
- A – Wrong. This is not a reduced breakdown, but increased production of ketone bodies in the liver.
- B – Correct. The combination of insulin deficiency (or its effect) with the increased action of glucagon leads to insufficient glucose utilization, gluconeogenesis and stimulation of lipolysis (enhancement of β-oxidation of fatty acids and overproduction of acetyl CoA in the liver).
- C – Wrong. The non-enzymatic conversion of acetoacetate to acetone, on the other hand, induces the possibility of ketone bodies also excreted by the lungs (smell of fruit in the breath).
- D – Right. Increased fatty acid catabolism in the liver, which arrives here from lipolysis from fat depots, leads to overproduction of acetyl CoA, which cannot be degraded in the citric acid cycle (lack of oxaloacetate formed during glycolysis); from the acetyl-CoA molecule is condensed to acetoacetyl-CoA, from which acetoacetate is formed; in the absence of O2, it can be reduced to hydroxybutyrate. Both carboxylic acids are moderately strong (pK around 4) and significantly affect blood pH in terms of acidemia.
- E – Correct. Increased production of acetyl-CoA in the liver, leads to the accumulation of condensation product - acetoacetate. Thus, it is an overproduction of ketone bodies in the liver, not a reduced degradation.
- F – Correct. The formation of hydroxymethylglutaryl-CoA (HMG-CoA) is one of the pathways from which acetoacetate is formed. Acetoacetyl-CoA takes up another molecule of acetyl CoA; this produces HMG-CoA, which cleaves acetyl-CoA by HMG-CoA lyase and remains "free" acetoacetate. This method of acetoacetate formation from aceto-acetyl-CoA appears to be more important than simple deacylation.
Question 9.
- A – Correct. Persistent severe hyperglycemia in noninsulin-dependent diabetes induces osmotic diuresis. In times of insufficient water supply, especially in the elderly after a stroke or infection, ECT hyperosmolarity occurs. Residual insulin secretion is sufficient to prevent excessive ketogenesis, but it is not sufficient to affect hyperglycemia. Hyperosmolar coma, therefore, occurs more frequently in noninsulin-independent diabetes; has a high mortality (up to 50%).
- B – Wrong. Lack of insulin combined with excess glucagon is the cause of ketoacidotic coma in IDDM. In NIDDM, residual insulin secretion prevents increased production of ketone bodies but does not prevent hyperglycemia.
- C – Wrong. Insulin does not affect the utilization of glucose by the brain.
- D – Wrong. Glycation of collagen in the basement membrane of glomeruli does cause increased permeability, which first leads to an increase in albuminuria as the first laboratory sign of incipient diabetic nephropathy; however, it does not cause osmotic diuresis.
Question 1.
- A – Wrong. Glucagon is not an enzyme, but a peptide hormone that raises blood glucose levels by glycogenolysis, stimulates gluconeogenesis and ketogenesis. The main target tissues are the liver.
- B – Wrong. Glucose-6-phosphate dehydrogenase is an enzyme that begins the breakdown of glucose by the pentosaphosphate cycle.
- C – Wrong. Glucokinase is a liver enzyme that phosphorylates glucose in the hepatocyte cytoplasm to glucose-6-phosphate. Its activity is greatly affected by glucose levels.
- D – Wrong. Hexokinase is an enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate in extrahepatic tissues. Hexokinase activity for a very low Km value is not affected by blood glucose concentration.
- E – Correct answer. Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to provide free glucose. It is present in the liver and kidneys. Missing (!) In muscle and adipose tissue. Its presence allows the supply of glucose from the tissues to the bloodstream.
Question 2.
- A – Wrong. Alanine can be metabolized to pyruvate by alanine aminotransferase catalysis, which then involves the formation of oxaloacetate with the participation of pyruvate carboxylase, Mg 2+ , ATP and CO 2 , and malate after reduction (everything takes place in mitochondria). This crosses the mitochondrial membrane (it is impermeable to oxaloacetate), it is again oxidized in the cytoplasm to oxaloacetate and it changes to phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase, GTP and CO 2 ..
- B – Wrong. Although pyruvate cannot be converted directly to phosphoenolpyruvate (pyruvate kinase can only work in one direction for thermodynamic reasons), phosphoenolpyruvate is formed again in the gluconeogenetic pathway via pyruvate carboxylase and phosphoenolpyruvate carboxykinases via oxaloacetate, malate and oxaloacetate again.
- C – Wrong. Lactate after dehydrogenation by lactate dehydrogenase gives pyruvate, which can be converted to phosphoenolpyruvate by "detonation", ie by gluconeogenesis enzymes (pyruvate carboxylase, phosphoenolpyruvate carboxykinase).
- D – Right. Palmitate undergoes β-oxidation and produces 8 acetylCoA, which in mitochondria can be further oxidized in the citrate cycle to CO 2 and H 2 O already in the first stages of the cycle, so there are not too many carbon residues converted to sufficient oxaloacetate needed for gluconeogenesis . Indeed, if oxaloacetate is removed from the cycle and not replaced, the cell's ability to produce much-needed ATP would be limited. Thus, acetyl-CoA is not a suitable substrate for gluconeogenesis; this is pyruvate formed from amino acids (alanine), which provides sufficient oxaloacetate by the reaction catalyzed by pyruvate carboxylase. Thus, gluconeogenesis does not interfere with metabolism in the citric acid cycle.
- E – Wrong. Oxaloacetate is an important substrate for gluconeogenesis. It is formed from pyruvate by the action of pyruvate carboxylase. However, it is impermeable across the mitochondrial membrane, so it must be converted to malate, which is permeable; in the cytoplasm, it is again dehydrogenated to oxaloacetate, which gives phosphoenolpyruvate with the participation of phosphoenolpyruvate carboxykinase; it provides glucose in the gluconeogenetic pathway via triosaphosphates and hexosaphosphates.
Question 3.
- A – Wrong. In contrast, insulin stimulates hepatic glucokinase activity and phosphorylates intracellular glucose to glucose-6-phosphate. This lowers the intracellular glucose level and thus indirectly promotes the flow of glucose from the circulation to the hepatocyte. Insulin promotes hepatic glycolysis. In contrast, it inhibits the activity of hepatic glucose-6-phosphatase, which releases glucose from the liver.
- B – Correct. Insulin promotes glucose utilization in muscle by promoting translocation of glucose through the circulatory system into the cell, further stimulating the production of glucose-6-phosphate, which can be isomerized to glucose-1-phosphate, a precursor for glycogen synthesis..
- C – Wrong. Insulin has the opposite effect, stimulates lipogenesis and is a very effective inhibitor of lipolysis.
- D – Wrong. Insulin, in turn, has the effect of promoting glycogen synthesis from glucose.
- E – Wrong. Insulin, on the other hand, stimulates the entry of amino acids into cells, stimulates protein synthesis (anabolic effect).
Question 4.
- A – Correct. The role of the Cori cycle (also the lactic acid cycle) is to transfer excess reducing equivalents from the muscles to the liver. In fast-moving muscles (during contraction), the supply of O 2 mitochondria is not fast enough to reoxidize the NADH formed during glycolysis. As the concentration of cytoplasmic NADH increases, lactate dehydrogenase catalyzes the transfer of reducing equivalents from NADH to pyruvate to form lactate. This penetrates from the muscles into the circulation and is taken up by the liver. In them, lactate dehydrogenase transfers electrons back to NAD to form pyruvate. In the gluconeogenetic pathway, pyruvate is converted into glucose, which leaves the liver and enters the muscles from the circulation. This cycle allows the skeletal muscles to work for a short time in anaerobic conditions.
- B – Wrong. Glucose-6-phosphate dehydrogenase is the initial enzyme that initiates the pentosaphosphate pathway of glucose metabolism.
- C – Wrong. Pyruvate dehydrogenase converts pyruvate to acetyl CoA, which enters the citric acid cycle. Before that, pyruvate cytoplasm must be transferred to the mitochondria. There, pyruvate undergoes oxidative decarboxylation catalyzed by a multienzyme complex, collectively called the pyruvate dehydrogenase complex.
- D – Wrong. Glucokinase catalyzes the phosphorylation of glucose in the liver to glucose-6-phosphate and thus initiates the glycolytic pathway.
- E – Wrong. Hydroxymethylglutaryl-CoA reductase is a key enzyme in cholesterol synthesis.
Question 5.
- A – decreases
- B – rising
- C – decreases
- D – rising
- E – decreases
Questiona 6.
- C – Correct. By binding to the surface membrane receptor, glucagon activates the adenylate cyclase system and thus increases the cAMP content in the cell (cAMP acts as a "second messenger"), thereby allosterically activating cAMP-dependent protein kinase, which converts phosphorylase b to active phosphorylase a, which cleaves glycogen in the liver (glycogenolytic effect of glucagon in the liver; not in muscle). Glycogen synthesis is inactivated (inactivated by protein phosphatase 1). After ingestion of food, glucose enters the vena portae, glucosemia rises; reaches its maximum in 30-60 minutes. In a healthy individual, the value does not exceed 10 mmol / l (usually 7-8 mmol / l).
Question 7.
- A – Correct. Absolute or relative lack of insulin prevents the transport of glucose across the cell membrane (excluding hepatocyte), reduces the activation of hexokinase and thus its phosphorylation to glucose-6-phosphate.
- B – Wrong. The site of gluconeogenesis is mainly the liver, not the muscles.
- C – Correct. Hepatic gluconeogenesis is significantly involved in hyperglycemia in diabetes. The main substrate of gluconeogenesis is amino acids (alanine), which is converted to pyruvate and by the gluconeogenetic pathway to glucose. The reaction requires energy, which is taken from the oxidation of fatty acids (lipolysis). Increased acetyl CoA production (β-oxidation of fatty acids) allosterically activates pyruvate carboxylase (an enzyme that initiates the conversion of pyruvate to phosphoenolpyruvate) and, conversely, inhibits pyruvate dehydrogenase, which is required for pyruvate (or acetyl CoA) to enter the citric acid cycle. Increased concentrations of alanine and fatty acids inhibit the conversion of phosphoenolpyruvate to pyruvate, thereby inhibiting glycolysis and promoting gluconeogenesis.
- D – Wrong. Glucose transfer to the hepatocyte is not insulin dependent. In other cells, this glucose carrier protein facilitates translocation of glucose across the membrane and requires insulin. Indirectly, however, insulin deficiency affects the entry of circulating glucose into the hepatocyte in diabetes by insufficiently activated glucokinase, which normally increases the gradient between "free" glucose outside and inside the liver cell.
- E – Wrong. An increase in the renal threshold for glucose occurs later in the course of diabetes and is a consequence of hyperglycemia rather than its primary cause. However, an increased renal threshold in advanced diabetes may contribute to the discrepancy finding of high hyperglycemia with relatively low glycosuria.
- F – Correct. In insulin deficiency, the effect of glucagon, which promotes hyperglycemia by increased hepatic glycogenolysis and stimulation of gluconeogenesis, predominates.
- G – Wrong. Insulin deficiency, on the other hand (due to relative glucagon excess), promotes lipolysis, which is needed as an energy source for gluconeogenesis.
Question 8.
- A – Wrong. This is not a reduced breakdown, but an increased production of ketone bodies in the liver.
- B – Correct. The combination of insulin deficiency (or its effect) with the increased action of glucagon leads to insufficient glucose utilization, gluconeogenesis and stimulation of lipolysis (enhancement of β-oxidation of fatty acids and overproduction of acetyl CoA in the liver).
- C – Wrong. The non-enzymatic conversion of acetoacetate to acetone, on the other hand, induces the possibility of ketone bodies also excreted by the lungs (smell of fruit in the breath).
- D – Right. Increased fatty acid catabolism in the liver, which arrives here from lipolysis from fat depots, leads to overproduction of acetyl CoA, which cannot be degraded in the citric acid cycle (lack of oxaloacetate formed during glycolysis); from the acetyl-CoA molecule is condensed to acetoacetyl-CoA, from which acetoacetate is formed; in the absence of O 2 it can be reduced to hydroxybutyrate. Both carboxylic acids are moderately strong (pK around 4) and significantly affect blood pH in terms of acidemia.
- E – Correct. Increased production of acetyl-CoA in the liver, leads to the accumulation of condensation product - acetoacetate. Thus, it is an overproduction of ketone bodies in the liver, not a reduced degradation.
- F – Correct. The formation of hydroxymethylglutaryl-CoA (HMG-CoA) is one of the pathways from which acetoacetate is formed. Acetoacetyl-CoA takes up another molecule of acetyl CoA; this produces HMG-CoA, which cleaves acetyl-CoA by HMG-CoA lyase and remains "free" acetoacetate. This method of acetoacetate formation from aceto-acetyl-CoA appears to be more important than simple deacylation.
Question 9.
- A – Correct. Persistent severe hyperglycemia in noninsulin-dependent diabetes induces osmotic diuresis. In times of insufficient water supply, especially in the elderly after a stroke or infection, ECT hyperosmolarity occurs. Residual insulin secretion is sufficient to prevent excessive ketogenesis, but it is not sufficient to affect hyperglycemia. Hyperosmolar coma therefore occurs more frequently in noninsulin-independent diabetes; has a high mortality (up to 50%).
- B – Wrong. Lack of insulin combined with excess glucagon is the cause of ketoacidotic coma in IDDM. In NIDDM, residual insulin secretion prevents increased production of ketone bodies, but does not prevent hyperglycemia.
- C – Wrong. Insulin does not affect the utilization of glucose by the brain.
- D – Wrong. Glycation of collagen in the basement membrane of glomeruli does cause increased permeability, which first leads to an increase in albuminuria as the first laboratory sign of incipient diabetic nephropathy; however, it does not cause osmotic diuresis.
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