Chapter 20 Clinical Enzymology

Front 1

Electrophoretic migration of isoenzymes forms the basis of standard nomenclature. Any isoenzyme designated '1' has what migration pattern?

Back 1

The number '1' isoenzyme is the one that migrates the farthest toward the anode. Recall that the anode is positively charged, so the protein that migrates farthest toward it will be the one which is most negatively charged.

Front 2

Michael is-Menten equation

Back 2

v=Vmax[S]//([S] +Km)

Front 3

In the Michaelis-Menten equation, what is the velocity of a reaction when KM = S?

Back 3

1/2 Vmax

Front 4

When enzyme activity is measured in a sample, the reaction rate, V, is set to proceed at maximum velocity, Vmax · Using the Michaelis-Menten equation , what substrate concentration will allow the reaction to proceed at Vmax?

Back 4

A substrate concentration much, much greater than the KM will achieve this:
S>>>KM

Front 5

In clinical laboratory reactions that measure enzyme activity, what order kinetics is occurring?

Back 5

This is zero-order kinetics . Any reaction can be pushed to zero-order kinetics by increasing the substrate concentration high enough.

Front 6

What is the utility of acid phosphatase (ACP) in screening for and monitoring prostate cancer?

Back 6

ACP is less sensitive than prostate-specific antigen (PSA) in screening and lacks specificity, being elevated in benign prostatic hyperplasia. However, it is unaffected by androgen levels and may be used to monitor for recurrence in men on androgen deprivation therapy.

Front 7

A 38-year-old woman who is blood group O demonstrates an increase in her alkaline phosphatas e (ALP) level of 26 IU/L from her baseline in a sample taken immediately after a meal. When will her ALP return to her baseline ? How about in the woman's 31-year-old, group O sister who just delivered a baby and has increased ALP due to the placental contribution?

Back 7

The 38-year-old woman's ALP will return to baseline in a short time (within an hour), as the t112 of intestinal ALP is just minutes. Her sister will take a few weeks to normalize, as the t1;2 of placental ALP is 7 days.

Front 8

An overweight black male smoker who takes phenobarbital for a seizure disorder
has an ALP of 147IU/L. Give four reasons for this individual having an ALP above the upper reference limit .

Back 8

Black males have about 15% higher ALP than white males. Obesity and smoking both increase total ALP. Tobacco contributes via pulmonary placenta­ like ALP. In patients on phenobarbital , the liver fraction is elevated.

Front 9

A 59-year-old woman who takes Prempro and smokes 1/2-l pack of cigarettes per day has an angiotensin-converting enzyme (ACE) level of 25 IU/L. Her twin sister, a nonsmoker who takes no medications, has an ACE level of 52 IU/L. How do you explain these results?

Back 9

Smokers have ACE levels which are roughly 30% lower than those in nonsmokers. Also, postmenopausal estrogen replacement lowers the ACE levels by 20%.

Front 10

True/False . While angiotensin-converting enzyme (ACE) levels are not specific for sarcoidosis, they are fairly sensitive indicators of disease activity.

Back 10

True. If a sarcoidosis patient is known to have an elevated ACE level, then it may be useful as a monitor of granuloma activity.

Front 11

Clinical Consultation: A military medical officer is deploying with a unit which may be exposed to organophosphates as a chemical weapon. Although the soldiers will take prophylaxis, the medical officer is preparing for the event of exposure.
Before the unit deploys, what laboratory test do you recommend and why?

Back 11

The members of the unit should have a baseline pseudocholinesterase level. There is significant inter-individual variation, and symptomatic persons may have levels which are technically within the reference range. However, a fall from one's baseline, or significant intra-individual variation, can be documented and is clinically useful in anticipating symptoms.

Front 12

For the following disorders, give the lactate dehydrogenase isoenzyme that is typically elevated.
Skeletal muscle injury:
Leukemia:
Hemolytic anemia:
Toxic hepatic injury:

Back 12

Skeletal muscle injury - LD5
Leukemia - LD3
Hemolytic anemia - LD 1
Toxic hepatic injury - LD5

Front 13

How useful are myoglobin assays compared to other tests in diagnosing rhabdomyolysis?

Back 13

Not very useful. This is due to the insensitivity of assays for myoglobin and its short half-life. A very high CK (some suggest 20 times the upper reference limit), coupled with markers of cell lysis such as potassium and phosphate, is a better approach.

Front 14

Competitive

A. Inhibitor binds to a site on the enzyme apart from the active site.
B. Inhibitor binds to the enzyme 's catalytic site.
C. Inhibitor binds to enzyme-substrate complex and prevents it from dissociating.
D. KM and Vmax are both reduced.
E. KM increases, Vmax is unchanged .
F. KM is unchanged, Vmax decreases.

Back 14

B,E

Front 15

Noncompetitive

A. Inhibitor binds to a site on the enzyme apart from the active site.
B. Inhibitor binds to the enzyme 's catalytic site.
C. Inhibitor binds to enzyme-substrate complex and prevents it from dissociating.
D. KM and Vmax are both reduced.
E. KM increases, Vmax is unchanged .
F. KM is unchanged, Vmax decreases.

Back 15

A,F

Front 16

Uncompetitive

A. Inhibitor binds to a site on the enzyme apart from the active site.
B. Inhibitor binds to the enzyme 's catalytic site.
C. Inhibitor binds to enzyme-substrate complex and prevents it from dissociating.
D. KM and Vmax are both reduced.
E. KM increases, Vmax is unchanged .
F. KM is unchanged, Vmax decreases.

Back 16

C,D