Active form of Calcium is Ionised Form

Question 35

Active form of Calcium is

a.       Ionised

b.      Albumin Bound

c.       Phos

d.      Protein

Answer

a. Ionised

Reference

Chaterjee 6^th Edition Page 538

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The serum level of calcium is closely regulated with a normal total calcium of 2.2-2.6 mmol/L (9-10.5 mg/dL) and a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL). The amount of total calcium varies with the level of serum albumin, a protein to which calcium is bound. The biologic effect of calcium is determined by the amount of ionized calcium, rather than the total calcium. Ionized calcium does not vary with the albumin level, and therefore it is useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level.

Explanation

Ionised calcium is physiologically active form of calcium.

Comments

Calcium is the most abundant mineral in the human body. The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of calcium phosphate salts. The extracellular fluid (ECF) contains approximately 22.5 mmol, of which about 9 mmol is in the serum. Approximately 500 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours

Tips

One can derive a corrected calcium level when the albumin is abnormal. This is to correct for the change in total calcium due to the change in albumin-bound calcium, and gives an estimate of what the calcium level would be if the albumin were within normal ranges.

    Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level.

When there is hypoalbuminemia (a lower than normal albumin), the corrected calcium level is higher than the total calcium.

The following are trypsin inhibitors alpha - 1 Anti trypsin alpha-1-anti proteinase Egg-white

Question 34

The following are trypsin inhibitors except..

a.       alpha - 1 Anti trypsin

b.      alpha-1-anti proteinase

c.       Enterokinase

d.      Egg-white

Answer

c. ENterokinase

Reference:

Harper 27^th Edition Page 597

Chaterjee 6^th Edition Page 398

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Trypsin is a proteinase. And can hydrolyze a peptide bond formed by the carbonyl group of a lysine residue on trypsinogen, converting the latter to trypsin and inactive hexapeptide

Explanation

a.       alpha - 1 Anti trypsin is the principal serine protease inhibitor of human plasma. It inhibits trypsin, elastase and certain other proteases forming complexes with them.

b.      alpha-1-anti proteinase is the new name for alpha - 1 Anti trypsin

c.       Enterokinase activates trypsinogen into trypsin in the presence of Calcium

d.      Egg-white is a trypsin inhibitor

Comments

Other trypsin inhibitors are

·        Human and bovin Colostrum

·        Raw SOyabeans

·        DFP (Di Iso propyl fluoro phosphate

Tips

Trypsin can be activated (ie trypsinogen converted to trypsin) by

·        Enterokinase

·        Trypsin itself (Autocatalytically)

Proteins are sorted by Golgi bodies

Question 33

Proteins are sorted by

a.       Golgi Bodies

b.      Mitochondria

c.       Ribosomes

d.      Nuclear Membranse

Answer:

a. Golgi bodies

Reference:

Harper 27^th Edition Page 506

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Proteins must travel from polyribosomes top many different sites in the cell to perform their particular functions. Some are destined to be components of specific organelles, others for the cytosol or for export and yet other will be located in the various cellular membranes. Thus there is considerable intracellular traffic of proteins. Many studies have shown that the Golgi apparatus plays a major role in sorting of proteins for their correct destination.

Explanation

Self Explanatory

Comments

The entire pathway of ERà Golfi apparatus à Plasma membrane is often called the secretory or exocytotic pathway. Secretory pathway involving transport vesicles is called “constitutive”

Tips

Other proteins destined for secretion are carried in secretory vesicles. These are prominent in pancreas and certain other glands. Their mobilization and discharge are regulated and often referred to as “regulated secretion”

Chaperones groups of proteins assist in the folding of other proteins

Question 32

Which of the following groups of proteins assist in the folding of other proteins?

1. Proteases.

2. Proteosomes.

3. Templates.

4. Chaperones

Answer

4. Chaperones

Reference

Harper 27^th Edition Pages 37, 515,

Textbook of Medical Biochemistry 4th Edition Chaterjee and Shinde Page 225

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The chaperones are proteins that play a role in the proper folding of other proteins without themselves being a compound of latter. They stabilize unfolded or partially folded intermediates, allowing them to fold properly and prevent inappropriate interactions. Few substances that can be called as chaperones include

a.       Calreticulin

b.      HSP 90A (Heat Shock Proteins)

c.       Synuclein alpha

d.      Lectin mannose binding 1

e.       DNA fragmentation factor 45

f.        Tubulin specific chaperone C

g.      Arylhydrocarbon-interacting receptor protein-like 1

h.      Tubulin specific chaperone D

i.        Unactive progesterone receptor 23KD (Yeah, That the name given - it is not printing mistake)

Explanation

1. Proteases are enzymes that hydrolyze proteins.

2. Proteosomes (especially the 26S component) help in degrading the proteins that are “marked” with Ubiquitin.

3. Template is involved in Synthesis of Nucleic Acids.

4. Chaperones are involved in Protein folding

Comments

Chaperonins are hsp60 family of chaperons

Tips

Few more points about Chaperones

1)      Present in many species

2)      Few are induced by conditions which cause unfolding of newly synthesized proteins

3)      Bind predominantly to Hydrophobic regions

4)      Act as Editing Mechanisms or Quality control

5)      Most have ATPase activity

6)      Found in

a)      Cytosol

b)     Mitochondria

c)      Lumen of Endoplasmic Reticulum

Okasaki Fragments are seen during the synthesis of ds DNA

Question 31

Okasaki Fragments are seen during the synthesis of

a.       ds DNA

b.      ss DNA

c.       m RNA

d.      t RNA

Answer

a. ds DNA

Reference:

Harper 26^th Edition Page 328, 27.335

Lippincott 3^rd Edition Page 403

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Discussion

An Okazaki fragment is a relatively short fragment of DNA (with an RNA primer at the 5' terminus) created on the lagging strand during DNA replication. It was originally discovered in 1968 by Reiji Okazaki, Tsuneko Okazaki, and their colleagues while studying replication of bacteriophage DNA in Escherichia coli.

The polymerase III holoenzyme (the dnaE gene product in E.Coli) binds to template DNA as part of a multiprotein complex that consists of several polymerase accessory factors (beta, gamma, delta, delta’ and theta). DNA polymerases only synthesize DNA in the 5’ to 3’ direction and only one of the several different types of polymerases is involved at the replication fork. Because the DNA Strands are antiparallel, the polymerase functions asymmetrically. On the leading (Forward) strand, the DNA is synthesized continuously.

Explanation

When the lagging strand is being replicated on the original strand, the 5'-3' pattern must be used; thus a small discontinuity occurs and an Okazaki Fragment forms. On the lagging (retrograde) strand, the DNA is systhesized in short (1-5kb) fragments, the so called Okazaki fragments. These fragments are processed by the replication machinery to produce a continuous strand of DNA and hence a complete daughter DNA helix.

Comments

Please note that synthesis of lagging strand involves DNA polymerase I, but the Okasaki fragments of the lagging strands are synthesized by DNA polymerase III

E.Coli	Mammalian	Function
I	a	Gap Filling and synthesis of lagging strand
II	e	DNA Proofreading and repair
	b	DNA repair
	g	Mitochondrial DNA synthesis
III	d	Processive leading strand synthesis

Tips

Reiji Okazaki  was a Japanese molecular biologist known for his research in DNA replication and especially for describing the role of so-called Okazaki fragments which he discovered working with his wife Tsuneko Okazaki in 1968.

Von Gierke disease - A child presents with Massive hepatomegaly, hypoglycemia, and there is no improvement with Glucagon.

Question 30

A child presents with Massive hepatomegaly, hypoglycemia, and there is no improvement with Glucagon. The probable diagnosis is

a.       Von Gierke disease

b.      Mcardle

c.       Cori

d.      Forbe

Answer

a) Von Gierke

Reference

Harper 27^th Edition Pages 166, 308, table 19.2

Table 73.1 Nelson 15^th Edition Table 350-1 Harrison 15^th Edition

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Glycogen storage disease type I or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase. This deficiency impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. Since these are the two principal metabolic mechanisms by which the liver supplies glucose to the rest of the body during periods of fasting, it causes severe hypoglycemia. Reduced glycogen breakdown results in increased glycogen storage in liver and kidneys, causing enlargement of both. Both organs function normally in childhood but are susceptible to a variety of problems in the adult years. Other metabolic derangements include lactic acidosis and hyperlipidemia. Frequent or continuous feedings of cornstarch or other carbohydrates are the principal treatment. Other therapeutic measures may be needed for associated problems.

Explanation

Self Explanatory

Comments

GSD No	Name	Enzyme Affected	Tissue Distribution of Excessive Glycogen and Enzyme Deficiency	Clinical Symptoms and Signs	Comments
GSD Ia	Von Gierke disease,	Glucose-6-phosphatase	Liver, kidney, intestine; frequent intranuclear glycogen seen in   these organs not diagnostic; continuous nighttime feeding by   tube and pump may alleviate clinical symptoms; portacaval   shunt risky and clinically disappointing; treatment with   phenytoin or phenobarbital ineffective	Enlarged liver and kidneys; "doll face," stunted growth,   normal mental development; tendency to hypoglycemia, lactic   acidosis, hyperlipidemia, hyperuric acidemia, gout, bleeding;   IV* galactose or fructose not converted to glucose (caution:   these tests may precipitate acidosis); abortive or no rise in   blood glucose after SC† epinephrine or IV glucagon; normal   urinary catecholamines; prognosis fair to good	hepatorenal glycogenosis; no   involvement of skeletal or cardiac muscle, or of leukocytes or   cultured skin fibroblasts (glucose-6-phosphatase not normally   present in these tissues)
GSD Ib		In vitro activity of glucose-6-phosphatase is     normal, but translocase is deficient	Activity of glucose-6-phosphatase is normal in frozen liver   homogenate but is not demonstrable in isotonic homogenate   of fresh liver tissue that has never been frozen	Symptoms are as those of GSD Ia; in addition, frequent   neutropenia	Transport defect for glucose-6-phosphate at microsomal   membrane
GSD Ic		In vitro activity of glucose-6-phosphatase     can be demonstrated	Activity of glucose-6-phosphatase is normal in frozen liver   homogenate but is deficient in isotonic homogenate of fresh   liver tissue that has never been frozen	The patient, an 11-yr–old girl, had hepatomegaly, brittle   diabetes, frequent hypoglycemia	Transport defect for inorganic phosphate at microsomal   membrane

Tips

The hypoglycemia of GSD I is termed "fasting", or "post-absorptive", meaning that it occurs after completion of digestion of a meal-- usually about 4 hours later. This inability to maintain adequate blood glucose levels during fasting results from the combined impairment of both glycogenolysis and gluconeogenesis. Fasting hypoglycemia is often the most significant problem in GSD I, and typically the problem that leads to the diagnosis. Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol.

Phosphorylase b is maintain in an inactivated state by Insulin

Question 29

Phosphorylase b is maintain in an inactivated state by

a.       ATP

b.      cAMP

c.       Calcium

d.      Insulin

Answer :

d. Insulin

Reference:

Harper 27^th Edition Page 162, Page 163 Figure 19.6 and Lippincott 3^rd Edition Page 131. Figure 11.11

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·        Phosphorylase is an enzyme give catalyses the following reaction

Glygogen(n+1) + Pi à Glycogen(n) + Glucose-1-Phosphate

·        Phosphorylase b is the inactive form and Phosphorylase a is the active form of the enzyme) The conversion of inactive phosphorylase to active phosphorylase (the reaction given below) is catalysed by phosphorylase kinase

Phosphorylase b + ATP à Phosphorylase a + ADP

·        Increasing the concentration of cAMP activates cAMP-dependant protein kinase which catalyses the phosphorylation by ATP of inactive phosphorylase kinase to active phosphorylase kinase

Phosphorylase kinase b + ATP à Phosphorylase kinase a + ADP

Explanation

·        We can see that the following factors active Phosphorylase b into phosphorylase a

·        ATP – Needed for phosphorylation of Phosphorylase b as well as phosphorylase kinase b

·        cAMP- Activates inactive cAMP depended protein kinase to active cAMP depended protein kinase so that phosphorylase kinase b is activated to phosphorylase kinase a

·        The conversion of Phosphorylase b to Phosphorylase (ie activation) in inhibited by

1.      G6P

2.      Insulin by virtue of it increasing the concentration of G-6-P

Comments:

If you are still not convinced, please read the table below

Action	Enzyme	Activated form	Inactivated form	Enzyme Activated from inactive form to active form by	Other factors needed
	cAMP-dependant protein kinase	inactive cAMP depended protein kinase	active cAMP depended protein kinase	cAMP
	Phosphorylase kinase	Phosphorylase kinase b	Phosphorylase kinase b	activates cAMP-dependant protein kinase	ATP Calcium Calmodulin component of phosphorylase kinase
Glycogenolysis	Phosphorylase a	Phosphorylase a	Phosphorylase b	Phosphorylase kinase a	ATP

Tips

What will you do if you have AMP instead of cAMP as one of the choices in another exam. Well there is nothing to worry as “in muscle under extreme conditions of anoxia and depletion of ATP, AMP activated glycogen phosphorylase b without it being phosphorylated

Muscle Glycogen in which part cannot contribute directly to Blood Glucose

Question 28

Glycogen in which part cannot contribute directly to Blood Glucose

a.       Liver

b.      Muscle

c.       Both

d.      None

Answer: 

b. Muscle

Reference:

Harper 27^th Edition Pages 142 & 162

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Muscle Glycogen cannot contribute directly to Plasma Glucose since muscle lacks glucose-6-phosphatase

Explanation

Self Explanatory

Comments

The primary purpose of muscle glycogen is to provide a source of Glucose-6-phosphate for energy yielding metabolism in muscle itself.

Tips

The major metabolic pathways in Muscle are

·        Fast Twitch Muscle - Glycolysis

·        Slow Twitch Muscle – beta oxidation and TCA

ATP does not form in.. HMP Pathway

Question 27

ATP does not form in..

a.       Glycolysis

b.      TCA Cycle

c.       Fatty Acid Oxidation

d.      HMP Pathway

Answer

d. HMP Pathway

Reference :

Harper 27^th edition Page 177

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The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not lead to formation of ATP but has two major functions

1.      The formation of NADPH for synthesis of fatty acids

2.      The formation of Ribose for nucleotide and nucleic acid formation

Explanation

Ä     Glycolysis leads to a net gain of 8 ATP per molecule of Glucose in aerobic conditions

Ä     TCA Cycle gives a net gain for 30 molecules per glucose molecule in aerobic conditions

Ä     Oxidation of fatty acids give ATP (the exact number depends on the fatty acid. Palmitic acid, for example, gives a net gain of 129 ATP. [(7cycles x 5per cycle) +  (8 Acetly CoA x12 per Acetyl CoA) – 2]

Comments

Pentose Phosphate Pathway is also called as

1.      Hexose Monophosphate pathway or Shunt

2.      Pentose Cycle

3.      Phosphogluconate pathway

4.      Warburg-Dickens0 Lipman Pathway

Tips

This pathway occurs in specialized tissues to serve specialized functions

1.      Liver

2.      Adipose Tissue

3.      RBC

4.      Testes

5.      Ovary

6.      Adrenal Cortex

7.      Lactating Mammary Glands