Enzymes Flashcards
What is an enzyme?
Protein that catalyze chemical reactions
What are isoenzymes?
Different enzyme structure but catalyze the same chemical reaction
What are isoforms?
Different structure is created by post-translational modification of the same gene product
What is the source of serum enzymes?
Cells: cytoplasm, mitochondria, membrane
What does serum enzyme activity increase?
Enzyme entry into plasma > inactivation/removal
What are the mechanisms of serum enzyme activity?
Increased release from damaged cells Induction of enzyme synthesis Cell proliferation--> more enzyme produced Decreased enzyme clearance Ingestion and absorption
What is decreased tissue mass associated with?
Decreased serum enzyme activity or concentration
Why does decreased activity of most enzymes not have diagnostic importance?
Poor sample handling
Presence of inhibitor in sample
Not appropriate reference interval for the patient
Decreased mass of origin tissue
What is the nomenclature for enzymes?
Name of substrate + type of reaction
What is the transfer of an amino group?
Transaminase
What is the transfer of amino group?
Kinase
What is oxidizing or reducing?
Oxidoreductases
When interpreting enzymes, what is the degree of increase determined by?
Patient’s value divided by the URL of the interval
What can indicate possible explanations when interpreting enzymes
Magnitude of increased enzyme activity
What does an ALT of 15x URL suggest?
Hepatocyte damage
What does an ALP of 10x URL indicate?
Too great from B-ALP, could be due to L- or C-ALP
Why should you consider the half life of enzymes?
CK has a shorter half life than AST
After a single injury, CK might return to the reference interval sooner
What is the significance of increased enzyme acitivities?
Markers or indicators of pathologic processes, not a specific diseae
What may the magnitude of increase of cytoplasmic enzymes relate to?
Severity of damage
What are the enzyme values with slight damage?
<2x URL
What are the enzyme values with severe damage?
> 50x URL
What does alanine transaminase (ALT/GPT) do?
Catalyzes deamination of alanine to form pyruvate –> can enter gluconeogenesis pathway or Krebs cycle
Where is ALT made?
Cytoplasmic enzyme:
Hepatocytes
Skeletal myocytes
What does it mean if there is increased ALT?
Hepatocyte damage
What are the most common causes of hepatocyte damage causing increased ALT?
Degenerative: hypoxia by anemia or congestion
Metabolic: lipidosis, diabetes, feline hyperthyroidism
Neoplastic: lymphoma, metastatic neoplasia, hepatocellular carcinoma
Infectious: lepto, histo, FIP, bacterial cholangiohepatitis
Inflammation of chronic hepatitis and cirrhosis
Toxic: steroid hepatopathy, anesthetic agents, tetracycline, carprofen, phenobarbital
Trauma: HBC
What is ALT a major marker of in dogs and cats?
Hepatocyte damage
What is ALT a major marker of in horses and cattles?
Hepatocytes heave very little ALT, thus it is not a useful marker
What does aspartate trasaminase (AST/GOT) do?
Catalyzes deamination of sspartate to form oxalacetate, which can enter the Krebs cycle
Where is AST made?
Cytoplasmic and mitochondrial enzyme: Hepatocytes Skeletal myocytes Cardiac myocytes Erythrocytes
What are causes of increased AST?
Hepatocyte damage
Skeletal or cardiac muscle damage
In vitro hemolysis or delayed removal of serum from clot: mild to moderate increase
What are the most common causes of hepatocyte damage causing increased AST in dogs and cats?
Same as ALT
What are the most common causes of hepatocyte damage causing increased AST in horses and cattle?
Degenerative: hypoxia by anemia, congestion, or cholelithiasis
Metabolic: lipidosis, diabetes mellitus, equine hyperlipidemia
Infectious: bacterial hepatitis, bacterial cholangiohepatitis, infectious necrotic hepatitis, hepatic abscess
What is AST a common marker for in horses and cattle?
Hepatocyte damage and muslce
What can AST be an indicator of? Why?
Active hepatocyte damage
It has a shorter half-life than ALT
What does lactate dehydrogenase (LD/LDH) do?
Catalyzes pyruvate to lactate in anaerobic glycolysis
Where is LD made?
Cytoplasmic: Hepatocytes Skeletal mycocytes Cardiac myocytes Erythrocytes
What is increased LD a marker for in all species?
Hepatocyte damage
Also increased by muscle damage and hemolysis
What conditions involved in hepatocyte damage increase LD?
Same as those listed for AST
What does iditol dehydrogenase (ID/SDH) do?
Catalyzes fructose to sorbitol
Where is ID made?
Cytoplasmic:
Hepatocytes
What causes increased serum activity of ID?
Hepatocyte damage
What species is ID primarily used in? What for?
Primarily used in horses and cattle: specific for the liver
What does glutamate dehydrogenase (GMD) do?
Catalyzes conversion of glutamate to 2-oxoglutarate
Where is GMD made?
Mitochondrial:
Mostly hepatocytes
Also present in other tissues
What increases the serum activity of GMD?
Hepatocyte damage
What is GMD a sensitive indicator of in dogs?
Hepatic diseases (mores sensitive than ALT, AST, ALP, and GGT)
What does alkaline phosphatase (ALP) do?
Phosphatase activity in an alkaline environment
What are the tissue sources of ALP?
Hepatocytes (L-ALP)
Biliary epithelium (L-LAP)
Osteoblasts (B-LAP)
Mammary epithelium
What is an increase in ALP in young animals due to?
B-LAP
Why do calves and pups have a higher ALP in the first days of age/
Colostrum intake
What are cause of increased ALP?
Cholestasis Induction by drugs or hormone Increased osteoblastic activity Canine mammary neoplasms Benign familial hyperphosphatemia in Suberian huskies
What is cholestasis primarily caused by?
Increased production of L-ALP by hepatocytes and biliary epithelium
In dogs, what do corticosteroids do to ALP?
Induce synthesis of L- and C-LAP
In pups, why is ALP increased?
B-ALP is typically mild
What is the ALP diagnostic sensitivity for detecting cholestasis in cats? Dogs? Horses? Cattle?
Poor in cats
High sensitivity in dogs
Poor in horses
Moderate in cattle
What does it mean if ALP has poor sensitivity for cholestasis?
Animal will be icteric before ALP increases
What does it mean if ALP has good sensitivity for cholestasis?
Animal will have an increase in ALP before being icteric
What happens to the ALP:GGT ratio in cats with lipidosis?
Increased; ALP increased more than GGT
What causes increased activities of ALP in hyperthyroid cats?
L-ALP and B-ALP
What does gamma-glutamyltransferase (GGT) do?
Catalyzes transfer of glutamyl groups between peptides and is involved in glutathione reactions
What is GGT associated with?
Cell membrane
What cells have GGT activity?
Biliary epithelial cells Hepatocytes Mammary epithelium Pancreatic acinar cells Renal tubular epithelial cells
What has a high activity of GGT in cattle?
Colostrum
Postsuckling calves have up to 16x the presuckling values
What are the values of GGT in pups compared to adults?
Values are up to 100x URL of adults
What may the synthesis of GGT be stimulated by?
Similar to ALP, increased constituents of bile
What is increased serum GGT activity associated with?
Drugs or hormones (phenobarbital)
What is a cause of hepatocyte damage in horses related to GGT?
Acute hepatocellular necrosis –> mild increase
In horses, what has better diagnostic activity for cholestasis, ALP or GGT? Cattle? Dogs?
GGT for horses and cattle
Probably ALP in dogs
What are the increases of GGT like in dogs with cholestatic diseases?
Tend to parallel increase in ALP activity
What causes GGT activity in urine?
Damage to renal epithelial cells increases urinary excretion of renal GGT and no changes in serum GGT
What does creatine kinase (CK) do?
Catalyzes transfer of phosphate from creatine-PO4 to adenosine diphosphate to form ATP
Where is CK made?
Cytoplasm of:
Skeletal mycocytes
Cardiac myocytes
Smooth muscle myocytes
What causes increased serum CK activity?
Damage to muscle fibers
Mild to marked increases in anorectic cats with nasophageal tubes
Hypothyroidism in dogs
In vitro hemolysis will cause falsely increased CK activity
Smooth muscle damage
What is the CK activity in animal with neurologic disease?
Brain and other tissues of CNS contain high CK activity
Necrosis or demyelination may cause increase CK activity
What does amylase (AMS) do?
Catalyzes hydrolysis of complex starches
Where is amylase made?
Cytoplasm:
Pancreatic acinar cells
What is the route of plasma AMS excretion or inactivation?
Kidneys
What causes increased AMS?
Pancreatic acinar cell damage
Decreased renal inactivation or excretion
What is the most common cause of pancreatic acinar cell damage?
Acute pancreatitis
What is the AMS value for dogs with pancreatic acinar cell damage?
WRI to >10x URI
What is the AMS value for cats with pancreatic acinar cell damage?
WRI to <3x
What does lipase (LPS) do?
Catalyzes hydrolysis of triglycerides
Where is LPS made?
Cytoplasmic:
Pancreatic acinar cells
Liver neoplasms
Gastric mucosa
What causes increased LPS?
Pancreatic acinar cell damage (acute pancreatitis)
Proliferation of cells in pancreatic or extrapancreatic neoplasia
Decreased renal inactivation or excretion
Dexmethasone treatment in dogs
What is the value of LPS in a dog with acute pancreatitis?
WRI to >10x URL
What is the value of LPS in a cat with spontaneous pancreatitis?
WRI to <5x URL
When is pancreatic lipase immunoreactivity (PLI) decreased?
Exocrin pancreatic insufficiency
What has the greater diagnostic sensitivity for pancreatitis, PLI, LPS, or TLI?
PLI
What was PLI like in cats with experimental pancreatitis?
PLI increased more and was more persistent than TLI
What has more diagnostic sensitivity for spontaneous pancreatitis, PLI, TLI, or abdominal US?
PLI
When is TLI increased?
Active pancreatitis
When is TLI decreased?
Exocrine pancreatic insufficiency
