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What is the primary reason for the higher alkaline phosphatase (ALP) levels observed in boys during childhood?
What is the primary reason for the higher alkaline phosphatase (ALP) levels observed in boys during childhood?
What effect does pregnancy have on alkaline phosphatase (ALP) levels?
What effect does pregnancy have on alkaline phosphatase (ALP) levels?
Which factor is associated with an increase in alkaline phosphatase (ALP) levels?
Which factor is associated with an increase in alkaline phosphatase (ALP) levels?
What is the effect of fibric acid derivatives on alkaline phosphatase (ALP)?
What is the effect of fibric acid derivatives on alkaline phosphatase (ALP)?
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How does smoking influence alkaline phosphatase (ALP) levels?
How does smoking influence alkaline phosphatase (ALP) levels?
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What is the primary source of GGT found in serum?
What is the primary source of GGT found in serum?
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In cases of biliary obstruction, how much can GGT levels increase compared to the upper reference limit (URL)?
In cases of biliary obstruction, how much can GGT levels increase compared to the upper reference limit (URL)?
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What condition is NOT associated with increased GGT levels?
What condition is NOT associated with increased GGT levels?
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What is the correlation between GGT levels and body weight?
What is the correlation between GGT levels and body weight?
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Which factor does NOT contribute to increased GGT levels?
Which factor does NOT contribute to increased GGT levels?
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What is the primary role of alkaline phosphatase (ALP) in cells?
What is the primary role of alkaline phosphatase (ALP) in cells?
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What is the significance of GGT as a biochemical marker?
What is the significance of GGT as a biochemical marker?
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Which enzyme isoform is primarily produced by osteoblasts?
Which enzyme isoform is primarily produced by osteoblasts?
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What increase in GGT activity is observed in infectious hepatitis?
What increase in GGT activity is observed in infectious hepatitis?
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Which of the following ions acts as an inhibitor of ALP activity?
Which of the following ions acts as an inhibitor of ALP activity?
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In what situation might GGT levels be transiently increased?
In what situation might GGT levels be transiently increased?
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Where is alkaline phosphatase predominantly located in hepatocytes?
Where is alkaline phosphatase predominantly located in hepatocytes?
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Which of the following genes codes for the intestinal isoform of ALP?
Which of the following genes codes for the intestinal isoform of ALP?
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What component is a constituent metal ion of ALP?
What component is a constituent metal ion of ALP?
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What physiological function does the tissue-nonspecific isozyme of ALP primarily serve?
What physiological function does the tissue-nonspecific isozyme of ALP primarily serve?
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Which type of ALP is produced following the ingestion of fatty foods?
Which type of ALP is produced following the ingestion of fatty foods?
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What is the half-life of prostatic ACP?
What is the half-life of prostatic ACP?
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Which factor can lead to falsely low values for tartrate-resistant ACP (TRAP) activity?
Which factor can lead to falsely low values for tartrate-resistant ACP (TRAP) activity?
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Why has the measurement of ACP become less popular for prostate cancer diagnosis?
Why has the measurement of ACP become less popular for prostate cancer diagnosis?
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What condition is NOT associated with elevated levels of ACP?
What condition is NOT associated with elevated levels of ACP?
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Which of the following best describes the reference range for serum ACP?
Which of the following best describes the reference range for serum ACP?
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What is the optimal pH range for NTP activity?
What is the optimal pH range for NTP activity?
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What is a significant drawback of using ACP for prostate cancer screening?
What is a significant drawback of using ACP for prostate cancer screening?
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In which condition is serum NTP activity likely to be increased?
In which condition is serum NTP activity likely to be increased?
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What is the primary method used to separate isoenzymes of ACP?
What is the primary method used to separate isoenzymes of ACP?
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Which statement is true regarding NTP and ALP activities?
Which statement is true regarding NTP and ALP activities?
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In which demographic does total and tartrate-resistant ACP levels typically increase?
In which demographic does total and tartrate-resistant ACP levels typically increase?
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What are the normal reference intervals for NTP activity at 37°C?
What are the normal reference intervals for NTP activity at 37°C?
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What is the expected change in NTP activity in cases of infectious hepatitis?
What is the expected change in NTP activity in cases of infectious hepatitis?
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What is the primary clinical significance of measuring NTP activity?
What is the primary clinical significance of measuring NTP activity?
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Which of these conditions might lead to increased serum NTP activity?
Which of these conditions might lead to increased serum NTP activity?
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How does NTP activity correlate with serum ALP in liver diseases?
How does NTP activity correlate with serum ALP in liver diseases?
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What is the primary source of increased alkaline phosphatase (ALP) activity in serum during hepatobiliary disease?
What is the primary source of increased alkaline phosphatase (ALP) activity in serum during hepatobiliary disease?
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Which isoenzyme of alkaline phosphatase has the shortest half-life?
Which isoenzyme of alkaline phosphatase has the shortest half-life?
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What factor is responsible for the release of alkaline phosphatase from cells during liver injury?
What factor is responsible for the release of alkaline phosphatase from cells during liver injury?
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Which condition is likely to cause a higher ALP activity due to extrahepatic obstruction?
Which condition is likely to cause a higher ALP activity due to extrahepatic obstruction?
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What percentage of day-to-day variability is associated with the bone isoenzyme of alkaline phosphatase?
What percentage of day-to-day variability is associated with the bone isoenzyme of alkaline phosphatase?
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Which forms of alkaline phosphatase are typically found in normal serum?
Which forms of alkaline phosphatase are typically found in normal serum?
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What is the approximate half-life of the liver isoenzyme of alkaline phosphatase?
What is the approximate half-life of the liver isoenzyme of alkaline phosphatase?
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In conditions of hepatobiliary disease, what types of ALP can be found in plasma?
In conditions of hepatobiliary disease, what types of ALP can be found in plasma?
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Study Notes
Clinical Enzymology
- This topic covers clinical enzymology, a subfield of clinical biochemistry.
Alkaline Phosphatase (ALP)
- ALP is a type of hydrolase enzyme.
- Multiple genes code for different ALP isoforms.
- Their physiological role isn't fully understood.
- Tissue-nonspecific isozyme is abundant in the kidney, liver, and bone.
- Post-translational modifications lead to different carbohydrate side chains in various tissues.
- Two other genes on chromosome 2 code for placental and intestinal ALP isoforms.
- Another gene codes for a germ cell/placental-like isoenzyme with similar properties to the placental isoenzyme.
- The enzyme is primarily bound to cell membranes, involved in phosphate cleavage, and facilitating substance transport.
- Hepatocytes produce ALP attached to the canalicular surface.
- Osteoblasts produce bone ALP, involved in pyrophosphate cleavage (an inhibitor of bone mineralization).
- Intestinal epithelial cells produce intestinal ALP, released after fatty food ingestion.
- Divalent ions like Mg2+, Co2+, and Mn2+ are ALP activators.
- Zn2+ is a constituent metal ion.
- Ions like phosphate, borate, oxalate, and cyanide are potent inhibitors.
- Diverse release mechanisms of ALP from cells result in various plasma forms.
- In liver injury, ALP synthesis increases.
- Bile acids dissolve canalicular membrane fragments.
- Normal serum typically has a single liver or bone form of ALP.
- Hepatobiliary disease shows both normal and attached membrane form ALP.
- Intestinal isoenzyme is released into duodenal fluid and lymphatic fluid after meals.
- ALP isoenzyme half-lives differ: intestine(minutes), bone(1 day), liver(3 days), and placenta(7 days).
- Day-to-day variation in total ALP is 5-10%, while bone isoenzyme shows 20% variability.
- Different locations of ALP in the body: liver (low in liver, high in biliary tree), intestine (renal tubular cells), placenta, and bone (osteoblast).
- ALP increases in serum are from liver or bone.
- Hepatobiliary disease and bone disease are ALP activity sources.
- Obstruction of biliary tracts causes ALP synthesis to increase by 10-12 times.
- Other sources of elevated serum ALP include advanced primary liver cancer, widespread secondary hepatic metastases, liver disease primarily affecting parenchymal cells, and primary biliary cirrhosis.
- Increased ALP is observed in pregnancy (up to two to three times URL).
- Benign transient ALP increases can be in infants and children.
- Carcinoplacental isoenzymes (like Regan isoenzyme) result from placental ALP gene de-repression.
- Different tumor types produce modified non-placental isoenzymes (like Kasahara isoenzyme).
- Increased osteoblastic activity (Paget disease, osteosarcoma, bone metastases, metabolic bone disease) elevates bone isoenzyme.
5'-Nucleotidase (5NT)
- 5' -Nucleotidase an enzyme acts only on nucleoside-5'-phosphates, releasing inorganic phosphate.
- Widely distributed in tissues, localized in cell membranes,
- pH optimum is between 6.6 and 7.0.
- Serum NTP activity appears to reflect hepatobiliary disease with high specificity (increases 3-6 fold).
- Elevated NTP is due to extrahepatic or intrahepatic conditions interfering with bile secretion.
- Serum NTP activity may be normal in approximately half of individuals with elevated liver ALP.
- Increased NTP in normal liver ALP suggests liver disease.
ɣ-Glutamyltransferase (GGT)
- GGT catalyzes the transfer of the γ-glutamyl group from peptides to acceptors.
- It acts only on peptides with a terminal glutamate residue.
- Found high in proximal renal tubule, liver, pancreas, and intestine.
- The enzyme is cytoplasmic and present in cell membranes, potentially transporting amino acids/peptides.
- Crucial for maintaining adequate intracellular glutathione (antioxidant).
- Serum GGT activity comes mainly from the liver, commonly rising in various forms of liver disease.
- Elevated in most subjects with liver illness, regardless of the cause.
- In biliary obstruction, GGT increases 5-30 times its upper reference limit (URL).
- Increased GGT is also found with increased body mass index, alcohol use, pregnancy, and anticonvulsant treatment.
- GGT activities show an independent prognostic value for cardiovascular morbidity and mortality, and have redox/pro-oxidant reactions in cell.
Acid Phosphatase (ACP)
- ACP is a hydrolase enzyme breaking down phosphate monoesters.
- All ACPs show optimal activity below pH 7.0.
- High concentration locations include prostate, liver, spleen, erythrocytes, and bone.
- Multiple forms with various molecular weights and tartrate sensitivities exist (e.g., lysosomal, prostatic, erythrocytic, macrophage, osteoclastic), crucial in bone remodeling.
- Serum ACP concentration is low, and erythrocyte ACP is differentiated from other types by inhibiting it with substances.
- A specific isoform of tartrate-resistant acid phosphatase (TRAP or TRAPase) is commonly found in osteoclasts and used to measure bone remodeling.
- A type of TRAP called TRAP-5b is of crucial interest, acting in bone remodeling.
- Serum ACP values depend on factors like age, gender, and hormone levels.
- Total ACP and tartrate-resistant ACP are higher in children.
- In women, total and tartrate-resistant activities increase after menopause.
- Prostatic ACP has a 1-3 hour half-life.
- ACP assays rely on hydrolysis to produce a measurable compound.
- Elevated ACP associated with prostate disease, though PSA is the primary test for it.
- Other potential causes include prostatic hyperplasia, malignancy, and urinary issues.
- Clinical conditions like prostatic massage, inflammation, infarction, and procedures like biopsies can lead to temporary increases.
- In suspected rape cases, vaginal fluid ACP provides a possible indicator.
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Description
This quiz focuses on alkaline phosphatase (ALP), a crucial hydrolase enzyme in clinical enzymology. Explore its various isoforms, genetic coding, physiological roles, and involvement in different tissues such as the liver, kidneys, and bone. Test your knowledge on the diverse functions and characteristics of ALP and its importance in clinical biochemistry.