Lab Test 3 - Clinical Enzymology

Question 1

Regulation of enzyme levels in serum and plasma

What determines the level of activity of the enzyme?

What are 2 crucial factors which determine the rate of entry of enzymes into the circulation from the cells of origin?

Answer 1

The balance between the rate of influx of active enzyme into the circulation and its eventual clearance from the blood determines the level of activity of the enzyme.

There are 2 crucial factors which determine the rate of entry of enzymes into the circulation from the cells of origin. The first being those that affect the rate of leak from the cells and the second are those that actually reflect altered rates of enzyme production, due to either increased synthesis of the enzyme in response to metabolic alterations in the cell or due to increased proliferation of the cell itself

Question 2

Leaking from the cells

As long as the integrity of the ___________ is maintained the enzymes do not leak out of the cell. This integrity is maintained by the cell’s _________.

What are 7 ways the ATP production of the cell can be hampered?

Answer 2

As long as the integrity of the plasma membrane is maintained the enzymes do not leak out of the cell. This integrity is maintained by the cell’s ATP production.

1. ATP production of the can be hampered in many ways:
2. The loss of oxygen carrying capacity and blood supply
3. Treatment with chemicals and drugs and other environmental pollutants
4. Extreme physical stress such as heat, radiation
5. Exposure to microbial agents and subsequent infection
6. Disruption or malfunction of the immune system
7. Genetic defects leading to metabolic disorders and nutritional disorders.

Question 3

Leaking from cells

The mitochondrial enzymes and others which are bound to the membranes of subcellular structures are not readily released into the________. Sensitive detection of such enzymes gives information to distinguish between damage only to the cell membrane from that of a ______ damage.

Answer 3

The mitochondrial enzymes and others which are bound to the membranes of subcellular structures are not readily released into the circulation. Sensitive detection of such enzymes gives information to distinguish between damage only to the cell membrane from that of a necrotic damage.

Question 4

Alteration in enzyme production

A basal level of __________ normally present in the plasma may be a result of wear and tear of cells or overflow of enzyme from healthy cells. A decrease in the levels may arise due to genetic deficiency such as in the case of ____ in hypophosphatasia or in case of diseased condition as in the case of decreased production of serum _________ in liver disease.

Answer 4

A basal level of intracellular enzymes normally present in the plasma may be a result of wear and tear of cells or overflow of enzyme from healthy cells. A decrease in the levels may arise due to genetic deficiency such as in the case of ALP in hypophosphatasia or in case of diseased condition as in the case of decreased production of serum cholinesterase in liver disease.

In diagnosis of disease, an increase of enzyme reduction is often more appreciated. However, the levels of enzymes and their isoenzymes often vary during a normal growth of an individual. The various isoenzymes of ALP provide us with a good example of such variations.

Question 5

Give examples when ALP increases and decreases and the diseases associated with it. In bone, placenta, liver, prostrate cancer,

Answer 5

For example bone alkaline phosphatase (bALP) is found to be increased in growing children and such increase in the bALP is also observed during an increased osteoblastic activity in bone diseases.

Similarly, placental ALP (pALP) production starts towards the end of a normal preganancy.

An increase in ALP production is seen by the liver during biliary obstruction.

In prostrate cancer, the acid phosphatase(ACP) levels increases due to the proliferating ACP-producing cells. However, this intial burst of ACP production may also decline if the cells metastasize far from the prostrate and the fast changing metastatic cells become more and more unlike the cell of origin and lose their ACP producing capability

Question 6

Clearance rate of enzymes

Most of the enzymes are removed from the circulation using the what mechanism and by what system? lWhere does this occur?

Since the enzymes are comparatively_______molecules, with the exception of ______, the clearance from the _______ of the kidney is not physically feasible. _______ is the only enzyme which is small enough to pass through the kidney. The half-lives of enzymes in plasma vary from hours to days averaging _____hours, When these enzymes complex with immunoglobulins, macroenzymes, the half-life ________ considerably.

Answer 6

Most of the enzymes are removed from the circulation using the mechanism of receptor mediated endocytosis via reticuloendothelial system largely involving in the bone marrow, spleen and the Kupffer cells of the liver and to some extent by nearly all other cells in the body.

Since the enzymes are comparatively larger molecules, with the exception of amylases, the clearance from the glomerulus of the kidney is not physically feasible. Amylase is the only enzyme which is small enough to pass through the kidney. The half-lives of enzymes in plasma vary from hours to days averaging 24-48 hours, When these enzymes complex with immunoglobulins, macroenzymes, the half-life increases considerably.

Question 7

Clearance rate of enzymes

The variation of clearance rate of enzymes and their isoforms varies under different pathological condition. Describe intestinal ALP as an example

Answer 7

The intestinal ALP(iALP) is a glycoprotein with a galactosyl terminal group. This is recognized by a galactosyl-specific receptor on the hepatocyte membrane and undergoes endocytosis. Due to this specificity in recognition, the process is very rapid and in normal conditions the half-life of iALP is very short. But in case of hepatic cirrhosis, the cell mass of the hepatocytic cells and consequently the receptors on its surface is considerable low, and this leads to an increase in the half-life iALP and reduced clearance rate.

Question 8

Troponins

What cardiac regulatory proteins control the calcium-mediated interaction of actin and myosin?

Studies performed with ____ have failed to find any ____outside of the heart at any stage of _______ development. In contrast, ____ is expressed to a minor extent in ______ muscle. However the present cTnT assay was not thought to detect these forms.

Young, healthy individuals without pathologic myocardial cell stress or damage are expected to have what in their blood?

Answer 8

Cardiac troponin 1(cTnl) and T(cTnT) are cardiac regulatory proteins that control the calcium-mediated interaction of actin and myosin. These proteins are products of specific genes and therefore have the potential to be unique for the heart.

Studies performed with cTnl have failed to find any cTnl outside of the heart at any stage of neonatal development. In contrast, cTnT is expressed to a minor extent in skeletal muscle. However the present cTnT assay was not thought to detect these forms.

Young, healthy individuals without pathologic myocardial cell stress or damage are expected to have little or no measurable troponin in their blood with any assay and with most assays presently in use this is the case. As troponin assays become more sensitive, however, it appears that healthy individuals do have tiny but detectable levels of troponin. Thus, defining the normal range is made difficult by out incomplete understanding of what a “normal” troponin really is.

Question 9

Troponins

With contemporary assays, individuals with increased values above the _______ URL are at hours after the onset of ____. By 2 or 3 hours after presentation, up to ____of patients with AMI will have troponin elevations. Rapidly appearing markers such as _______ and __ isoforms, appear to provide little additional information when used together with a sensitive assay for troponin. Elevations in ____ and____ after an AMI persist for up to __ days, thus permitting late diagnosis. Troponins can also be used for detecting_______

Answer 9

With contemporary assays, individuals with increased values above the 99th percentile URL are at hours after the onset of AMI. By 2 or 3 hours after presentation, up to 80% of patients with AMI will have troponin elevations. Rapidly appearing markers such as myeoglobin and CK isoforms, appear to provide little additional information when used together with a sensitive assay for troponin. Elevations n cTnT and cTnl after an AMI persist for up to 10 days, thus permitting late diagnosis. Troponins can also be used for detecting reinfarction

Question 10

Creatine Kinase

The enzyme creatinine kinase(or creatnine phosphokinase) exists as isoenzymes which are dimers of what chains and exist in how many combinations?

Where do these enzymes reside and what do they facilitate?

Where is this activity of CK distributed?

Describe normal range of CK and elevations

Answer 10

The enzyme creatinine kinase(or creatnine phosphokinase) exists as isoenzymes which are dimers of M and B chains and exist in 3 combinations; MM, MB and BB.

These isoenzymes reside in the cytosol and facilitate the egress of high-energy phosphates into and out of mitochondria.

Creatnine Kinase(CK) isoenzyme activity is distributed in many tissues, including skeletal muscle, but there is more of the CK-MB fraction in the heart. Most muscles have more CK per gram than heart tissue. Thus, skeletal muscle breakdown can lead to absolute increases in CK-MB in the plasma.

Elevations in total serum CK lack specificity for cardiac damage, which improves with measurement of the MB fraction. The normal range of CK also varies considerable; twofold or greater increase in the CK concentration is required for diagnosis.

Question 11

Creatnine Kinase

When cardiac tropoinin is available, _____ should not be used for the diagnosis of __________. If it is the only assay available, it can be used but is far less sensitive and specific. Most assays measure CK-MB ____, which is more sensitive than activity assays. In addition, mass assays avoid, for the most part, detection of ___________(CK linked to IgG and dimers of mitochondrial CK) that can confound diagnosis with activity assays. The presence of macrokinases should be considered, as one possibility, when CK-MB is a very high%( greater than ____) of total CK.

Answer 11

When cardiac tropoinin is available, CK-MB should not be used for the diagnosis of acute myocardial infarction. If its is the only assay available, it can be used available, it can be used but is far less sensitive and specific. Most assays measure CK-MB mass, which is more sensitive than activity assays. In addition, mass assays avoid, for the most part, detection of macrokinases(CK linked to IgG and dimers of mitochondrial CK) that can confound diagnosis with activity assays. The presence of macrokinases should be considered, as one possibility, when CK-MB is a very high%( greater than 20%) of total CK.

Question 12

Creatnine Kinase

Elevated creatnine kinase may be caused by conditions including:

Answer 12

Brain injury

Delirium tremens(severe alcohol withdrawal)

Muscle diseases such as dermatomyositis, polymyositis or msucular dystrophy

Myocardial infarction(heart attack)

Myocarditis(infection of the middle layer of the heart wall)

Rhabdomyolysis(muscle destruction)

Stroke

Trauma

Hypothyroid subjects

Cerebral ischemia

Question 13

Aminotransferases

What do transaminases catalyze?

What does AST catalyze?

What are normal serum values of AST and ALT? The activites of both AST and ALT are high in which tissues?

Answer 13

Transminases are present in most of the tissues of the body. They catalyze the interconversions of the amino acids and 2-oxacids by transfer of amino groups.

AST catalyzes the interconversion of oxaloacetate to aspartate coupled with glutamate ot oxoglutarate.

Normal serum values: AST(SGOT) - 0-30 IU/L and ALT(SGPT)- 0-30IU/L. In newborns value up to 120 units for AST and 90 units for ALT is considered normal. The activites of both AST and ALT are high in tissues especially liver, heart and muscles. Any damage or injury to the cells of these tissues may cause release of these enzymes along with other intracellular proteins/enzymes into the circulation leading to increase activites of these enzymes in the blood

Question 14

Aminotransferases

Determinations of activites of ___ and ___ in serum in patients with liver diseases like_______ and other forms of liver disease with _____, give high values even before the apprearance of clinical signs and symptoms like _____. Activity levels of ______fold higher than normal are frequently seen in liver cells damage but it may reach as high as _____ times in severe damage to cells. Some increase in the activities of ALT and AST are seen in extrahepatic_______. In ______ the level of activites vary with the severity of the disease. It may increase only up to ___fold of the normal activites. Up to ___fold increase is seen in carcinoma of the liver.

Answer 14

Determinations of activites of AST and ALT in serum in patients with liver diseases like viral hepatitis and other forms of liver disease with necrosis, give high values even befoe the apprearance of clinical signs and symptoms like jaundice. Activity levels of 20 to 50 fold higher than normal are frequently seen in liver cells damage but it may reach as high as 100 times in severe damage to cells. Some increase in the activies of ALT and AST are seen in extrahepatic cholestasis. In cirrhosis the level of activites vary with the severity of the disease. It may increase only up to 5 fold of the normal activites. Up to 10 fold increase is seen in carcinoma of the liver.

Question 15

Aminotransferases

In what problems do AST and ocassionally ALT activity levels rise? Is there is increase in the enzyme activity in the muscle diseases of neurogenic origin? Describe the levels? What about levels after crushed muscle injuries?

The _____ ratio is approximately ___ in normal subjects. In some settings, this ratio changes in characteristic ways that may sugest a diagnosis. In particular, the AST is greater than the ____ in alcoholic hepatitis and ratio greater than ____ is suggestive of this disorder. Smaller increases in the ratio to values greater than ___ occur in other causes of cirrhosis but not in most other liver diseases.

Answer 15

AST and occasionally ALT activity levels are increased in progressive muscular dystrophy and dermatomyositis. Level of AST may go as high as 8 times of the normal. There is no increase in the enzyme activity in the muscle diseases of neurogenic origin. Increased AST activity, 2 to 5 times of normal, is also seen after crushed muscle injuries

The AST/ALT ratio is approximately 0.8 in normal subjects. In some settings, this ratio changes in characteristic ways that may sugest a diagnosis. In particular, the AST is greater than the ALT in alcoholic hepatitis and ratio greater than 2:1 is suggestive of this disorder. Smaller increases in the ratio to values greater than 1.0 occur in other causes of cirrhosis but not in most other liver diseases.

Question 16

Aminotransferases

Striking increases(exceeding 1000 U/L or 50 times the upper limit of normal) are most commonly seen in what?

On rare occasions, similar values suggesting acute hepatitis can be seen in a number of 4 settings:

Answer 16

Striking increases(exceeding 1000 U/L or 50 times the upper limit of normal) are most commonly seen in acute viral hepatitis, shock liver(ischemic hepatitis), and acute drug- or toxin-induced liver injury (eg-acetaminophen intoxication).

On rare occasions, similar values suggesting acute hepatitis can be seen in a number of settings:

1. During an acure exacerbation of autoimmune chronic active hepatits
2. Spontaneous reactivation of chronic type B hepatitis
3. Superimposition of delta hepatits in a chronic carrier of hepatitis B virus infection
4. Miscellaneous disorders such as acute Budd-Chiari syndrome(especially those with concomitant portal vein thrombosis), veno-occlusive disease, HELLP syndrome, actue fatty liver of pregnancy and hepatic infarction

Question 17

Aminotransferases

The following 6 conditions can be associated with elevated aminotransferase levels without liver disease:

Answer 17

The followig conditions can be associated with elevated aminotransferase levels without liver disease:

1. False positive elevations in the AST in patients receiving erythromycin estolate or paraminosalicyclic acid and during diabetic ketoacidosis when AST was measured using a calorimetric assay
2. Primary muscle disease in which livver disease has been excluded by serologic tests and/or normal liver biopsy. A concurrent increase in creatnine phosphokinase(CPK) , LDH or aldolase levels suggests a primary muscle source
3. Macro AST in which AST complexes with immunoglobin, usually IgG. This rare finsing is analogous to macroamylasemia and often leads to diagnostic confusion
4. Subclinical celiac disease
5. Hypothyroidism and hyperthyroidism
6. Adrenal insufficiency

Question 18

Lactate dehydrogenase(LDH)

What does Lactase dehydrogenase catalyze?

Why is LDH widely distributed iN tissues? How many subunits does LDH is have and how many types? How many isoenzymes?

In what tissues are each isoenzymes distributed?

What is thenormal serum value?

Answer 18

Lactate dehyrogenase catalyzes the oxidation of L-lactate to pyruvate. In the reaction hydrogen is transferred from lactate with the mediation of NAD+ as hydrogen acceptor.

LDH is widely distributed in more of the tissues as it is one of the glycolytic enzymes active under hypoxic condition.

LDH is composed of 4 subunits of 2 types ie. H and M(H for heart and M for muscles). There are 5 isoenzymes with different subunit composition names as LDH1 to LDH5.

Isoenzymes are predominantly distributed in the tissue specific manner, LDH1 and 2 are predominantly present in cardiac muscles, kidney and erythrocytes. LDH4 and 5 isoenzymes are predominant in liver and skeletal muscle. LDH2, 3 and 4 are found in many other tissues like spleen, lungs, endocrine glands, platelets etc.

Normal serum value: 60-200 IU/L

Question 19

Lactate dehydrogenase

Describe the Elevation

Answer 19

• Myocardial infarction. The level of total LDH activity in serum is 3-4 times that of normal but it may go up to 10 times the normal value (not used as a marker of MI!)
• myocarditis and cardiac failure with hepatic congestion
• Toxic hepatitis with jaundice
• vrial hepatits
• chronic glomerulonephritis, systemic lupus erythematosus, diabteic nephrosclerosis
• bladder and kifney malignancies. Patients with malignant disease show increased LDH activity in serum especially LDH4 and 5
• germ cell tumors like tertomas, seminoma of the testis high level of LDH1 is seen

Question 20

Alkaline phosphatase

Alkaline phosphatase are present in almost all tissues of the body. They are membrane bound and are___ containing ________. They hydrolyze a variety of organic phosphate esters transferring ________from a donor substrate to an acceptor containing a ________. _____ levels of enzyme are present in intestinal epithelium (I), Kidney tubules(K), osteoblasts in the bone(B), bile canalicular and sinusoidal membrane of the liver(L), placenta and lactating breast(P).

Answer 20

Alkaline phosphatase are present in almost all tissues of the body. They are membrane bound and are zinc containing metalloenzymes. They hydrolyze a variety of organic phosphate esters transferring phosphate groups from a donor substrate to an acceptor containing a hydroxyl group. High levels of enzyme are present in intestinal epithelium (I), Kidney tubules(K), osteoblasts in the bone(B), bile canalicular and sinusoidal membrane of the liver(L), placenta and lactating breast(P).

Question 21

Alkaline phosphatase

___________ are a group of true isoenzymes, encoded by at least __different genes; tissue non-specific intestinal placental and germ line ALP. The______ derived from the tissue ______ isoenzyme by post translational modificaton include the variants of the enzyme found in the____, ____, ___ and the ____. Some malignant tumors can produce a placental form of the enzyme called the_________. In serum of normal adults most of the enzyme activity is contributed by ____ and nearly half by ____, Normal serum value- _______

Answer 21

Alkaline phosphatases are a group of true isoenzymes, encoded by at least 4 different genes; tissue non-specific intestinal placental and germ line ALP. The isoforms derived from the tissue non-specific isoenzyme by post translational modificaton include the variants of th enzym found in the liver, bone, kidney and the placenta. Some malignant tumors can produce a placental form of the enzyme called the Regan’s isoenzymes. In serum of normal adults most of the enzyme activity is contributed by liver and nearby half by bone, Normal serum value- 35-101 Ul/L

Question 22

Alkaline phosphatase

Physiological bone growth elevates___ in sera and hence in the serum of growing children enzyme activity is ______ times that in normal ______ serum. The level of ALP in the serum of _________ is ______ times more than that of normal level

Answer 22

Physiological bone growth elevates ALP in sera and hence in the serum of growing children enzyme activity is 1.5-2.5 times that in normal adult serum. The level of ALP in the serum of women in the 3rd trimester of pregnancy is 2-3 times more than that of normal level

Question 23

Alakine Phosphatase

Elevation

Answer 23

• Biliary obnstruction due to any cause
• Extrahepatic obstruction by stones or by carcinoma head of pancreas
• Infectious hepatitis-only moderate elevation
• bone diseases with increases osteoblastic activity
• Paget’s disease
• Osteomalacia, rickets
• Fanconi’s syndrome. primary and secondary hyperparathyroidism

Question 24

Acid Phosphatase

Where is acid phosphatase found?

The male prostrate gland has ___times more acid phosphatase than any other body tissue. Tissues other than prostrate, have small amounts of acid phosphatase, including ____, liver, spleen, kidney, and ______ and platelets.

Acid phosphatase from prostrate contributes to how much of the enzyme activity present in the serum of a healthy male? What is the normal serum value?

Answer 24

Acid phosphatase is an enzyme found throughout the body but primarily in the prostrate gland. The male prostrate gland has 100 times more acid phosphatase than any other body tissue. Tissues other than prostrate, have small amounts if acid phosphatase, including bone, liver, spleen, kidney, and red blood cells and platelets.

Different forms of acid phosphatase are found in different organs and their serum levels are used as a diagnosic for disease in the corresponding organs. Acid phosphatase from prostrate contributes to 1/3rd to 1/2 of the enzyme activity present in the serum of a healthy male. Normal serum value-0.1-0.63 Ul/L

Question 25

Acid phosphatase Elevation

Answer 25

* The highest levels of acid phosphatase are found in metastasized prostrate cancer, It is of clinical importanceto differentiate prostatic and nonprostatic form of acid phosphatase. the prostatic enzyme is strongly inhibited by dextrorotatory tartrate ions, wheras the erythrocyte isoenzyme is not. Formaldehyde and cupric ions inhibit erythrocyte acid phosphatase but not the prostrate acid phosphatase * diseases of the bone such as pagets disease * hyperparathyroidism * diseases of blood cells such as sickle cell disease or mutiple myeloma * lysosomal disorders such as Gaucher's disease

Question 26

Prostrate specific antigen(PSA) Where is PSA expressed? What is the absolute value of serum PSA useful for?

Answer 26

PSA is a glycoprotein that is **expressed** by both normal and neoplastic tissue. PSA is consistently **expressed** in nearly all prostrate cancers, although its level of expression on a per cell basis, especially in very **poorly differentiated prostrate cancers**, **is lower** than in normal prostrate epithelium. The **absolute value of serum PSA** is useful for determining the extent of prostrate cancer and assessing the response to prostate cancer treatment; its use as a screening method to detect prostate cancer is also common, lthough controversial.

Question 27

Prostrate specific antigen (PSA) Under _____ conditions, PSA is produced as a \_\_\_\_\_(proPSA) by the secreoty cells that line the prostrate glands(acini) and secreted into the\_\_\_\_, where the propeptide is removed to generate\_\_\_\_\_\_. The active PSA can then undergo ______ to generate ______ PSA of which a small portion then enters the _______ and circulates in an unbound state (free PSA). Alternatively, active PSA can diffuse directly into the circulation where it is rapidly bound by protease inhibitors, including\_\_\_\_\_\_\_\_(ACT) and \_\_\_\_\_\_\_.

Answer 27

Under **normal** conditions, PSA is produced as a **proenzyme**(proPSA) by the secreoty cells that line the prostrate glands(acini) and secreted into the **lumen**, where the propeptide is removed to generate **active PSA**. The active PSA can then undergo **proteolysis** to generate **inactive PSA** of which a small portion then enters the **bloodstream** and circulates in an unbound state(free PSA). Alternatively, active PSA can diffuse directly into the circulation where it is rapidly bound by protease inhibitors, including **alpa-1-antichymotrypsin(ACT) and alpha-2-macroglobulin.**

Question 28

Prostrate specific antigen (PSA) In men with a normal prostrate(ie no cancer and no major inflammation/infection), the majority of free PSA in the serum reflects....... In contrast, this cleaved fraction is relatively decreased in prostrate cancer, Thus, the % of free or unbound PSA is lower in the serum of men with prostrate cancer(and conversely the amount of complexed PSA is higher) compared to..... This finding has been exploited in the use of the ratio of\_\_\_\_\_\_\_\_\_as a means of distinguishing between prostrate cancer and _____ as a cause of an elevated PSA.

Answer 28

In men with a normal prostrate(ie no cancer and no major inflmmation/infection), the majority of free PSA in the serum **reflects** the mature protein that has been inactivated by internal proteolytic cleavage. In contrast, this cleaved fraction is relatively decreased in prostrate cancer, Thus, the % of free or unbound PSA is lower in the serum of men with prostrate cancer(and conversely the amount of complexed PSA is higher) compared with those who have a normal prostrate or BPH. This finding has been exploited in the use of the ratio of **free to total PSA and complexed PSA(cPSA**) as a means of distinguishing between prostrate cancer and **BPH** as a cause of an elevated PSA.

Question 29

Prostrate specific antigen (PSA) In men without prostrate cancer, serum PSA reflects. As prostrate size increases with age what happens? As a result, different normal reference ranges may be appropriate based upon a man's age. Describe the ranges.

Answer 29

In men without prostrate cancer, serum PSA **reflects** the amount of glandular epithelium, which in turn reflects prostrate size. Thus as prostrate size increases with increasing age, the **PSA concentration also raises**. The **serum PSA** concentration increased by aproximately **3.2%(0.04ng/mL) per year** for a healthy **60** year old. As a result, different normal reference ranges may be appropriate based upon a man's age. The following ranges have been suggested: * 40 to 49 years old - 0 to 2.0 ng/mL(blacks); 0 to 2.5(whites) * 50 to 59 years old - 0 to 4.0 ng/mL(blacks); 0 to 3.5 (whites) * 60 to 69 years old - 0 to 4.5 ng/mL(blacks); 0 to 3.5(whites) * 70 to 79 years old - 0 to 5.5 ng/mL(blacks; 0 to 3.5(whites)

Question 30

Prostrate specific antigen (PSA)

Answer 30

Elevation * benign prostatic hyperplasia(BPH) * prostrate cancer * prostatic inflammation/infection * perineal trauma

Question 31

y-Glutamyltransferase (GGT) \_\_\_\_ comes under the peptidase group of enzymes which specifically catalyzes the transfer of\_\_\_\_\_\_\_\_group from peptides and other compounds that contain it to the substrate itself, same amino acid or peptide, or even ____ in which case a simple hydrolysis takes place. GGT is present in serum which originates primarily from the \_\_\_\_\_\_\_system. It is present in all the cells except those in \_\_\_\_\_\_. It is predominantly located in the cell membrane and may act to transport aino acids and peptides into the cell in the form of y-glutamyl peptides. Normal serum value-\_\_\_\_\_\_\_\_\_

Answer 31

**GGT** comes under the peptidase group of enzymes which specifically catalyzes the transfer of **y-glutamyl** group from peptides and other compounds that contain it to the substrate itself, sime amino acid or peptide, or even **water** in which case a simple hydrolysis takes place. GGT is present in serum which originates prmarily from the **hepato-biliary** system. It is presnt in all the cells except those in **muscle**. It is predominantly located in the cell membrane and may act to transport aino acids and peptides into the cell in the form of y-glutamyl peptides. Normal serum value - **M:18-100 Ul/L, F: 10-66Ul/L**

Question 32

y-Glutamyltransferase associated with hepatobiliary obstruction (GGT) Elevation

Answer 32

Elevation * all forms of liver disease * intra- and post-hepatic biliary obstruction, obstructice jaundice, cholangitis and cholecystits * primary and secondary liver cancer * alcoholic liver cirrhosis * anticonvulsant drugs * acute as well as chronic pancreatits * in some cases of pancreatic malignancies especially if associated with hepatobiliary obstruction

Question 33

Amylase

Answer 33

* group of hydrolases that hyrdrolyze complex carbohydrates containing a-D glucse units linked through carbon 1 and 4 located on adjacent glucose residues * both straight chain and branched polyglucans are hydrolyze at a1,4 linkages. * The branch points(a1,6-linkages) are not attacked by the enzyme * requires calium ions and activated by Chloride and Bromide, ph optimum is 7 * serum amylase molecular weight is 55 to 60kDa * highest concentration in pancreas, through pancreatic duct it is secreted into the intestinal tract

Question 34

Amylase Describe amylase in saliva Where else is amylase present? Serum amylase is mainly contributed by _____ (P type) and _____ gland(S-type) and \_\_\_\_\_\_in urine is derived from \_\_\_\_\_\_. Even after pancreatectomy the level of _______ amylase activity is not ________ much as the salivary glands and other sources contribute to the serum amylase activity.

Answer 34

Salivary gland secretes amylase in the mouth where the hydrolysis of starch takes place while food is still in the mouth, The saliary enzymes become inactive when it reaches the stomach due to the presence of acids. Amylase activity is also in striated muscle, adipose tissue, lung,ovaries, fallopian tubes, semen and testes. The enzyme is secreted in milk, colostrums and tears, Tumors of lung and ovary, ascetic fluid due to pacncreatic tumor may ontain amyulase. Serum amylase is mainly contributed by pancreatic **(P type) and salivary gland(S-type) and amylase in urine** is derived from **plasma**. Even after pancreatectomy the level of **serum** amylase activity is not **reduced** much as the salivary glands and other sources contribute to the serum amylase activity.

Question 35

Amylase In the serum of \_\_\_\_\_\_\_\_\_patients, macroamylase is present. It is probably a complex of ordinary amlyase and other high molecular weight plasma proteins like \_\_\_, ____ and other molecules. It is not filtered in the\_\_\_\_\_ and increases serum amylase activity by \_\_\_\_\_folds. Amlyase activity in the\_\_\_\_ is found to be lower than normal. No clinical symptoms are however associates with this disorder. The differentiation of macroamylases from the ________ serum amylase in eg, acute pancreatitis is most simply made by determination of the _________ which will be increased if the amylase is of the usual molecular weight

Answer 35

In the serum of **macroamylasemia** patients, macroamylase is presnt. It is probably a complex of **ordinary amlyase** and other **high molecular weight plasma proteins** like **IgA, IgG** and other molecules. It is not filtered in the kidneys and increases serum amylase activity by **6 to 8 folds.** Amlyase activity in the **urine** is found to be lower than normal. No clinical symptoms are however associates with this disorder. The differentiation of macroamylases from the **increased** serum amylase in eg, acute pancreatitis is most simply made by determination of the **urinary amylase** which will be increased if the amylase is of the usual molecular weight

Question 36

Amylase Amylase activity assay in \_\_\_\_and \_\_\_\_are mainly done in the investigation of the _____ function and the diagnosis of diseases of the pancreas. In acute pancreatitis, serum amylase activity increased within \_\_\_\_\_\_hours of the onset of the disease with maximal levels in _____ hours and the level returns to normal by ______ day, There is \_\_\_\_\_\_fold increased in amylase activity above a reference limit. However, up to ___ of the cases may have _____ amylase activity in the serum. A significant amount of serum amylase is excreted un the urine, so the ____ of serum amylase is reflected in the rise of urine amylase activity. In quiescent chronic pancreatitis both the serum and urine amylase activity is found to be \_\_\_\_\_\_

Answer 36

Amylase activity assay in **serum and urine** are mainly done in the investigation of the **pancreatic** function and the diagnosis of diseases of the pancreas. In acute pancreatitis, serum amylase activity increased within **2 to 12** hours of the onset of the disease with maximal levels in **12-72** hours and the level returns to normal by **3rd or 4th day**, There is **4 to 6 fold** increased in amylase activity above a reference limit. However, up to **20%** of the cases may have **normal** amylase activity in the serum. A significant amount of srum amylase is excreted un the urine, so the **rise** of serum amylase is reflected in he rise of urine amylase activity. In quiescent chronic pancreatitis both the serum and urine amylase activity is found to be **subnormal**

Question 37

Lipases Lipases are enzymes that hydrolyze\_\_\_\_\_\_\_esters of long chain fatty acids. Lipase activity in the serum and other body fluid is measured exclusively for ________ disroders, In acute pancreatitis, increased lipase activity in the serum is seen after ____ hours of an attack, peaks at about ___ hours, and come to normal level by _____ days. Increased lipase activity parallels that of amylase but lipase activity may increase sooner and remain longer than that of \_\_\_\_\_activity in the serum and the extent of rise is higher with lipase activity. As\_\_\_\_ cases of acute pancreatits show\_\_\_\_\_ amylase activity, it is necessary to estimate both the \_\_\_\_\_\_\_\_\_\_activity in ther serum of a patient suspected of acute pancreatitis. Other conditions in which high serum lipase activity is seen are ______ of the pancreatic duct by calculus or by ______ of the pancreas, acute and chronic ______ diseases.

Answer 37

Lipases are enzymes that hydrolyze **glycerol** esters of long chain fatty acids. Lipase activity in the serum and other body fluid is measured exclusively for **pancreatic** disroders, In acute pancreatitis, increased lipase activity in the serum is seen after **4 to 8** hours of an attack, peaks at about **24** hours, and come to normal level by **8 to 14** days. Increased lipase activity parallels that of amylase but lipase activity may increase sooner and remain longer than that of **amylase** activity in the serum and the extent of rise is higher with lipase activity. As **20%** cases of acute pancreatits show **normal** amylase activity, it is necessary to estimate both the **amylase and lipase** activity in ther serum of a patient suspected of acute pancreatitis. Other conditions in which high serum lipoase activity is seen are **obstruction** of the pancreatic duct by calculus or by **carcinoma** of the pancreas, acute and chronic **renal** diseases.