Carbohydrate Metabolism [Part 2] (Viva)

Q.1 What is hexose monophosphate pathway or shunt?

It is an alternate pathway of glucose oxidation that takes place in certain special tissues to serve certain special functions.

Q.2 How does HMP shunt differ from the EM pathway?

Essential differentiating points are:

HMP shunt  EM pathway
Occurs in certain special tissues only Occurs in all tissues 
A multicyclic process Not so
NADP+ acts as H-acceptor  NAD+ acts as H-acceptor
ATP is not produced pathway. Not meant for energy Energy producing. ATP is produced.
CO2 is formed CO2 is never formed.



Q.3 In which part of the cell HMP shunt operates?

In the cytosol


Q.4 Why HMP shunt is called as a multicyclic process and what are the products.

It is called a multicyclic process, as 3 mols of glucose-6-P enter the cycle, producing 3 mols of CO2-, 6 mols of NADHP, and 3 mols of 5- C residues which rearrange to give 2 mols of glucose-6-P (re-enters the cycle) and one mol of glyceraldehyde-3-P.

Q.5 Which is the key and rate-limiting enzyme in HMP shunt?

Glucose-6-phosphate dehydrogenase (G-6- PD)

Q.6 What is the role of thiamine in HMP shunt?

TPP the active form of thiamine is required as a coenzyme with “transketolase” enzyme for two transketolation reactions.

Q.7 Name the tetrose sugar formed in HMP shunt.

Erythrose-4-P.

Q.8 How does the NADP+/NADPH ratio regulate HMP shunt?

  • If the ratio is high, it enhances the rate-limiting reaction and shunt pathway.
  • If the ratio is low, it inhibits G-6-PD and 6-phosphogluconate dehydrogenase enzymes and decreases the shunt pathway.

Q.9 State the hormones that regulate HMP shunt.

  • Insulin: It induces the synthesis of dehydrogenase enzymes and enhances the activity of the pathway.
  • Thyroid hormones: It stimulates the activity of the G-6-PD enzyme of the pathway.

Q.10 State the metabolic role of HMP shunt.

  • Does not produce energy.
  • Provides NADPH: required for various reductive synthesis.
  • Provides pentoses: required for nucleic acid synthesis.
  • Role in lens metabolism: Provides reduced glutathione (G-SH) necessary for the maintenance of lens proteins.
  • Role in RB Cells: Provides reduced glutathione (G-SH)) necessary for RB cells membrane integrity.
  • CO2 is produced which is used in CO2 fixation reaction.

Q.11 Mention some metabolic reactions where NADPH is used for reductive processes.

NADPH is used in a number of metabolic processes where it provides hydrogen for reductive synthesis, e.g.

  • Extramitochondrial de novo fatty acid synthesis.
  • In synthesis of cholesterol.
  • In synthesis of steroids.
  • In conversion of oxidized glutathione to reduced glutathione.
  • For conversion of phenylalanine to tyrosine.
  • For conversion of methemoglobin→Hb.
  • In synthesis of sphingolipids.
  • In “microsomal” chain elongation of FA.
  • In uronic acid pathway.

Q.12 Muscle tissues contain very small amounts of the dehydrogenases enzymes but still skeletal muscle is capable of synthesizing pentose sugars. How?

Probably this is achieved by the reversal of shunt Pathway utilizing fructose-6-P, glyceraldehyde-3-P, and the enzymes transketolase and transaldolase (by nonoxidative Pathway).

Q.13 What is Wernicke-Korsakoff syndrome?

  • A genetically variant form of transketolase occurs which cannot bind TPP thus affecting transketolation reaction.
  • The patient shows severe neuropsychiatric symptoms characterized by lesions and hemorrhages near the IIIrd ventricle.
  • The patient shows deranged mental function, loss of memory, depression, disorientation, and mental confusion.

Q.14 What is galactosemia?

Excretion of galactose in urine due to the deficiency of enzyme galactose-1-PO4 uridyl transferase leads to a condition known as galactosemia.

Q.15 State the salient clinical features in galactosemia.

  • Infants appear normal at birth but later: – fails to thrive – becomes lethargic and may vomit. – develops hypoglycemia and – may develop jaundice.
  • After 2 to 3 months: – develops cataracts in both eyes. – shows mental retardation due to the accumulation of galactose and galactose-IP in the cerebral cortex. – liver may have fatty infiltration and produces cirrhosis liver.

Q.16 What is the cause of cataracts in galactosemia?

Excess of galactose in the lens of the eye is reduced to “galactitol” (Dulcitol), an alcohol by the enzyme aldose reductase. Galactitol cannot escape from lens cells. Osmotic effect of sugar alcohol contributes to injury to lens proteins producing cataracts.

Excess of galactose inhibits the enzyme G-6-PD of HMP shunt leading to less NADPH which results to low reduced glutathione (G-SH).

Q.17 What are the enzymes deficient in galactosemia?

Enzymes deficient are: a Galactose kinase. b. Galactose-1-PO4-uridyl transferase.

Q.18 What is the uronic acid pathway?

It is an alternative pathway for glucose oxidation. This pathway also does not produce energy.

Q.19 What is the metabolic significance of the uronic acid pathway.

  • Formation of D-glucuronic acid which is used for detoxication.
  • Produces vitamin C in lower animals, but cannot synthesize vitamin C in man, and other primates including G. pigs due to the absence of enzymatic machinery.
  • Inherited deficiency of the enzyme “Lxylitol dehydrogenase” produces essential pentosuria.
  • Excessive xylitol or parenteral administration of xylitol may lead to oxalosis.

Q.20 What are the metabolic functions of D-glucuronic acid produced in the uronic acid pathway?

Detoxication: Detoxicates drugs, chemicals, antibiotics, hormones, etc convert them to corresponding soluble glucuronides which are excreted.

Examples:

– Aromatic acid-like benzoic acid.

– Phenol and secondary/tertiary aliphatic alcohols.

– Drugs and other xenobiotics

—they are first hydroxylated by mono-oxygenase cyt.P450 system and then conjugated with-D-glucuronic acid.

– Antibiotics like chloramphenicol.

– Steroid hormones and thyroid hormones.

– Bile pigments: unconjugated bilirubin is conjugated with UDP-glucuronic acid and converted to soluble mono and diglucuronides.

– Synthesis of heteroglycans containing D-glucuronic acid, e.g. heparin, hyaluronic acid, chondroitin SO4.

Q.21 Name some drugs which increase the formation of D-glucuronic acid by uronic acid pathway.

  • Barbiturates
  • Amino Pyrine and
  • Antipyrine

 Q.22 What is true glucose?

True glucose means glucose only without taking into account the presence of any other reducing substances in the blood.

Q.23 Name some dietary sources of fructose.

The principal source is sucrose (cane sugar/ table sugar), which on hydrolysis in the intestine gives fructose.

Other sources are fruit juices and honey.

Q.24 Name the specific enzyme that phosphorylates fructose and the product formed.

  • Specific enzyme is fructokinase.
  • Product is fructose-1-P.

Q.25 State some metabolic importance of fructose.

  • Fructose is easily metabolized and a good source of energy.
  • Seminal fluid is rich in fructose and spermatozoa utilizes fructose for energy.
  • Excess dietary fructose is harmful, leads to increased synthesis of TG.
  • In diabetes mellitus, fructose metabolism through the sorbitol pathway may account for the development of cataracts and neuropathy.
  • Inherited deficiency of the enzyme “aldolase-B” produces an inherited disorder hereditary fructose intolerance.

Q.26 How is glucose converted to fructose in seminiferous tubular epithelial cells?

  • It is achieved by the sorbitol pathway.
  • Sorbitol pathway for conversion of glucose to fructose is shown schematically.

Q.27 How do you explain biochemically the formation of cataract and neuropathies in diabetes mellitus?

Formation of sorbitol from glucose by the sorbitol pathway proceeds rapidly in the lens of the eye and Schwann cells of the nervous system.

Elevated sorbitol concentration in these cells increases the osmotic pressure which may be responsible for the development of cataracts of the lens of the eye and diabetic neuropathy.

Q.28 What is hereditary fructose intolerance?

It is an inherited disorder, due to inherited deficiency of the enzyme aldolase B. It leads to excessive rises of fructose- and fructose1-P in blood.

Blood glucose falls leading to hypoglycemia. The cause of hypoglycemia is probably due to:
– excessive insulin secretion and
– inhibition of phosphoglucomutase enzyme, by fructose-1-P

Diets low in fructose and sucrose are beneficial.

Q.29 How will you estimate true glucose?

True glucose is estimated by the glucose oxidase method.

Q.30 What is the use of glucose vial?

Glucose vial is used to collect blood for the estimation of glucose level.

Q.31 Glucose vial constitutes?

It contains sodium fluoride and potassium oxalate in a 1:3 ratio. Sodium fluoride inhibits glycolysis and potassium oxalate inhibits coagulation of blood.

Q.32 What are the different methods of measuring reducing sugars levels?

  1. Reduction method:
    - King and Asatoor method
    - Folin and Wil method
    - Ferricyanide method.
  1. Orthotoluidine method.
  2. Enzymatic method.
  3. Dextrostick method.

Q.33 What is the normal blood sugar level?

80-100 mg%.

Q.34 What is glucose postprandial level?

Glucose postprandial level is 100-140 mg%.

Q.35 What are the different types of glucose transporters?

GLUT-1 Brain, kidney, RBC
GLUT-2 Liver, pancreas
GLUT-3 Kidney, placenta
GLUT-4 Heart, skeletal muscle, adipose tissue
GLUT-5 Small intestine
SGLT-1 Small intestine and kidney

 

Q.36 What are the conditions in which blood sugar level is low?

 Blood sugar level is low in:

  1. Overdosage of insulin in the treatment of diabetes.
  2. Hypothyroidism.
  3. Addison’s disease.

Q.37 What are the conditions in which blood sugar level is raised?

Conditions in which blood sugar level is raised are.

  1. Diabetes mellitus.
  2. Hyperthyroidism.
  3. Hyperadrenalism.
  4. Hyperpituitarism.
  5. Thyrotoxicosis.

Q.38 What is the kidney threshold for glucose?

180 mg

Q.39 What is TMG?

The maximum rate at which glucose can be resorbed from the tubule is called TMG.

Q.40 What are the hormones which keep the blood sugar level high?

  1. Glucagon.
  2. Epinephrine.
  3. Adrenal cortex hormones.
  4. Growth hormone and ACTH.
  5. Thyroid hormone

Q.41 What is the hormone which regulates blood sugar level?

Insulin

Q.42 Why insulin cannot be given orally?

Insulin is a polypeptide and is digested by the enzymes of the digestive system into amino acids before it reaches in the blood. Hence, it cannot be given orally.

Q.43 What is renal glycosuria?

As a result of low kidney threshold, glucose appears in the urine. Blood sugar level remains normal.

Q.44 What is diabetes mellitus?

Diabetes Mellitus is a metabolic disorder due to the deficiency of insulin, resulting in high blood glucose levels and glucose excretion in the urine.

Q.45 What are the types of diabetes mellitus?

Two types:

  1. Insulin-dependent diabetes mellitus (IDDM)
  2. Non-insulin-dependent diabetes mellitus (NIDDM).

Q.46 What is IDDM?

In this disease, there is autoimmune destruction of b-cells of the pancreas and it is also known as juvenile diabetes.

Q.47 What is NIDDM?

In this disease, there is resistance to insulin so in spite of normal or elevated levels of insulin hyperglycemia occurs.

Q.48 What is diabetes insipidus?

Lack of ADH (antidiuretic hormone) gives rise to a condition known as diabetes insipidus. The patient may excrete urine up to 30 liters/day.

Q.49 What is the abnormality in the urine sample of diabetic patients and the urine sample of starving patients?

In diabetic patients, urine will show the presence of glucose and ketone bodies; Whereas in the case of the starving patient, only ketone bodies will be present in the urine.

Q.50 What are the different reducing sugars that appear in urine and under what conditions?

Glucose:
Appears in urine in renal glycosuria and diabetes mellitus.
Lactose:
During later stages of pregnancy and lactation.
Galactose:
In galactosemia due to the deficiency of the enzyme galactose-1-PO4 uridyl transferase. This condition is encountered in infants.
Fructose:
Due to the consumption of a lot of fruits containing fructose such as grapes, plums, cherry, etc
Pentoses:
Due to the consumption of a lot of fruits containing pentoses. Also in congenital abnormality characterized by the inability to metabolize L-xylulose.

 

Q.51 How the collection of blood specimens is done for estimating blood glucose?

The blood sample is collected in potassium oxalate: sodium fluoride bottle.

Q.52 What is the function of each?

Sodium fluoride: It prevents glycolysis by inhibiting the enzyme Enolase of the glycolytic pathway.

Potassium oxalate: It acts as an anticoagulant.

Q.53 What is the role of isotonic CuSO4 in blood sugar estimation?

Isotonic CuSO4 prevents the hemolysis of red blood cells so that glutathione which is present in the red blood cells does not come out, otherwise will also reduce the alkaline CuSO4 and give rise to high blood sugar values.

Q.54 What are the functions of insulin?

  1. Insulin promotes the entry of glucose in all the tissues of the body except the liver.
  2. Insulin helps in glycogenesis.
  3. Insulin prevents glycogenolysis.
  4. Insulin inhibits gluconeogenic enzymes.

Q.55 How glucose is removed from the blood?

Oxidation of glucose in tissues to provide energy.
Hepatic glycogenesis.
Glycogenesis in muscles and other tissues.
Conversion to fat (lipogenesis) in adipose tissue mainly.
For synthesis of lactose, fructose, ribose sugars, glycoproteins, glycolipids, MPs etc.
Excretion in urine when blood glucose exceeds the renal threshold (abnormal condition).

 

Q.56 What is the role of insulin on carbohydrate metabolism?

The net effect produces a fall in blood glucose concentration.

Diminished supply of glucose to blood due to:
– decrease hepatic glycogenolysis
– increased hepatic glycogenesis.
– Decreased gluconeogenesis

Increased in the rate of utilization of glucose by tissue cells:
– increased uptake by tissues
– increased oxidation for energy
– increased lipogenesis

Q.57 Name the emergency hormones which increase blood glucose.

  • Catecholamines viz. epinephrine and norepinephrine.
  • Glucagon.

 Q.58 What is hyperglycemia?

An increase in blood glucose levels above normal is called hyperglycemia.

Q.59 Enumerate some causes of hyperglycemia.

  • Diabetes mellitus.
  • Hyperactivity of thyroids (thyrotoxicosis), anterior pituitary (acromegaly/ gigantism), and adrenal cortex (Cushing’s syndrome).
  • In diffuse diseases of the pancreas, e.g. in pancreatitis, carcinoma of pancreas.
  • In sepsis and in some infectious diseases.
  • In intracranial diseases, e.g. meningitis, encephalitis, intracranial tumors, and hemorrhage.
  • In emotional ‘stress’.

Q.60 What is hypoglycemia?

A decrease in blood glucose level below normal is called hypoglycemia.

Note: Hypoglycemia manifests clinically when the blood glucose is below < 40 mg % (“true” glucose).

 Q.61 Enumerate some causes of hypoglycemia.

  • Overdosage of insulin in the treatment of DM—most common cause and clinically important.
  • Hypoactivity of thyroids (myxoedema, cretinism), anterior pituitary (Simmond’s disease), and adrenal cortex (Addison’s disease).
  • Insulin secreting tumor (insulinoma)— rare cause.
  • In severe liver diseases.
  • Leucine sensitive hypoglycemia.
  • Glycogen storage diseases (GSDs).
  • Idiopathic hypoglycemia in children.
  • Nonendocrine tumors like retroperitoneal fibrosarcoma can produce insulin-like hormones.

Q.62 State important biochemical changes that occur in an untreated uncontrolled DM.

Hyperglycemia: Increase in blood glucose.
Glycosuria: Excretion of glucose in urine.
Hypercholesterolemia: Increase in blood cholesterol.
Ketonemia: Increased ketone bodies in blood-acetoacetic acid, β OH-butyric acid, and acetone.
Increased urea and nonprotein nitrogen in blood.
Dehydration.
Acidosis: Lowered pH, hyperventilation (Metabolic), and Kussmaul breathing.
Lowered HCO3 and alkali reserve.
Lowered sodium in blood
—hyponatremia and disturbance in fluid and electrolyte balance.

 

Q.63 What is meant by glucose tolerance?

The ability of the body to utilize glucose is ascertained by measuring its glucose tolerance. It is indicated by the nature of the blood glucose curve following the administration of a standard dose of glucose.

Q.64 Name some conditions where you find decreased glucose tolerance.

  • Diabetes mellitus.
  • Hyperthyroidism.
  • Hyperactivity of adrenal cortex and anterior pituitary.

Q.65 Name some conditions where you find increased glucose tolerance.

  • Hypothyroidism,
  • Hypofunction of adrenal cortex (Addison’s disease),
  • Hypopituitarism,
  • Hyperinsulinism,
  • Decreased absorption of glucose like sprue/celiac disease, etc.

 Q.66 How will you perform a standard glucose tolerance test (GTT)?

A ‘fasting’ sample of venous blood is collected in a fluoride bottle (“fasting” sample of blood).
The bladder is completely emptied and urine is collected for qualitative tests for glucose and ketone bodies (“fasting” urine).
The individual is given 75 gm of glucose dissolved approximately 250 ml of water to drink orally. The time of oral glucose administration is noted.
A total of five specimens of venous blood and urine are collected every ½ hr, after the oral glucose (½ hr, 1 hr, 2 hr, and 2½ hr samples of blood and urine).
The glucose content of all six (including fasting sample) samples of blood are estimated. Corresponding urine samples are tested qualitatively for glucose and ketone bodies.
The results of blood glucose values are plotted as a graph against time. The curve thus obtained is called the glucose tolerance curve.

 

Q.66.1 Describe a typical normal glucose tolerance curve (GTC).

Fasting glucose is within normal limits of 60 to 100 mg % (“true” glucose).

The highest peak value is reached within one hour.

The highest value does not exceed the renal threshold, i.e. 170 to 180 mg%.

At 2 hr, there is a hypoglycaemic dip (10 to 15 mg lower than fasting value).

The fasting level is reached by 2½ hr.

No glucose or ketone bodies are detected in any specimens of urine.

Q.67 Describe a diabetic type of GTC.

  • Fasting blood glucose is definitely raised >110 mg% (“true” glucose).
  • The highest value is usually reached after 1 to 1½ hr.
  • The highest value exceeds the normal renal threshold. The blood glucose does not return to the fasting level within 2½ hr, remains much higher than the fasting value. Thie is the most characteristic feature of DM.
  • Urine samples show the presence of glucose. Urine may or may not contain ketone bodies depending on the type of DM and its severity.
  • According to severity, the GTC may be:
  • Mild diabetic curve.
  • Moderately severe diabetic curve.
  • Servere diabetic curve.

Q.68 What is primary lactose, Intolerance?

It is a hereditary deficiency of lactose, most commonly found in persons of Asian and African deserts.

Common symptoms of lactose Intolerance Include vomiting, bloating, cramps, watery diarrhea, and dehydration. Diagnosis is based on a positive hydrogen breath test after an oral lactose load.

Q.69 What is secondary lactose intolerance?

It is precipitated at any age by gastrointestinal disturbances such as celiac sprue, colitis, or viral-induced damage to intestinal mucosa.

Q.70 What is the treatment for lactose intolerance?

Dietary restriction of milk and milk products or using drug-like lactose pills.

Q.71 What is galactokinase?

  1. Galatosemia
  2. Galatosuria
  3. Cataract in early childhood.

Q.72 What is the treatment of galactokinase deficiency?

Eliminate the source of galactose from the diet. Avoid dairy products.

Q.73 What is essential fructosuria?

It is a genetic deficiency of fructokinase and is usually benign. There is a presence of fructose in the urine.

Q.74 What is hereditary fructose intolerance?

It is one of the serious diseases resulting due to the accumulation of fructose I-phosphate in the liver and in the proximal tubule in the kidney. Present with vomiting, apathy, liver damage can lead to jaundice. Renal Damage can lead to Fanconi like syndrome and severe hypoglycemia.

Q.75 What is the treatment for hereditary fructose intolerance?

Eliminate fructose from diet.

Q.76 Explain Pompe’s disease.

In this disease, there is a deficiency by lysosomal L-1,4 glucosidase. It is Infantile onset and death usually occur by 2 years.

Q.77 Explain Cori’s disease.

In this disease, there is a deficiency of glycogen debranching enzyme.