The correct answer for the first question is B. α1-Antitrypsin (AAT) deficiency. This is a genetic disorder that can cause pulmonary damage and emphysema even without the use of cigarettes. When there is a deficiency of AAT, elastase activity is increased, leading to the destruction of elastin in the alveolar walls. AAT deficiency is suspected when a patient younger than 45 years old develops chronic obstructive pulmonary disease without a history of chronic bronchitis or tobacco use, or when multiple family members develop obstructive lung disease at an early age. Choices A, C, and E refer to collagen, not elastin.

For the second question, the correct answer is C. The child most likely has osteogenesis imperfecta. This condition is often caused by a defect in the genes responsible for encoding type I collagen. Affected patients have thin, osteoporotic, and frequently bowed bones that are prone to fractures. The presence of blue sclerae is also noted. There is no pulmonary involvement in this case. Marfan disease is characterized by impaired structural integrity in the skeleton, eyes, and cardiovascular system due to defects in fibrillin. Defects in type V collagen lead to the classic form of Ehlers-Danlos syndrome, which is characterized by skin extensibility, fragility, and joint hypermobility. Scurvy, caused by vitamin C deficiency, is characterized by capillary fragility.

Regarding the liver and lung pathology in α1-antitrypsin deficiency, the cirrhosis seen is a result of polymerization and retention of AAT in the liver, where it is synthesized. In the lung, the deficiency of AAT leads to alveolar damage due to the unopposed activity of elastase, a serine protease.

Proline hydroxylation in collagen occurs through the action of prolyl hydroxylase, an enzyme found in the endoplasmic reticulum. This process requires oxygen, ferrous iron, and vitamin C. Hydroxylation of proline increases interchain hydrogen bond formation, strengthening the triple helix structure of collagen. Vitamin C deficiency impairs the hydroxylation process.

Enzymes play a crucial role in mediating virtually all reactions in the body. These protein catalysts increase the rate of reactions without being altered in the overall process. By selectively directing substrates into useful pathways, enzymes control and regulate all metabolic events. This chapter examines the nature of enzymes as catalytic molecules and explores their mechanisms of action.

Each enzyme is assigned two names. The first is the recommended name, which is more convenient for everyday use. The second is the systematic name, used when precise identification of an enzyme is necessary.
Correct answer = B. α1-Antitrypsin (AAT) deficiency is a genetic disorder that can cause pulmonary damage and emphysema even in the absence of cigarette use. A deficiency of AAT permits increased elastase activity to destroy elastin in the alveolar walls. AAT deficiency should be suspected when chronic obstructive pulmonary disease develops in a patient younger than age 45 years who does not have a history of chronic bronchitis or tobacco use or when multiple family members develop obstructive lung disease at an early age. Choices A, C, and E refer to collagen, not elastin.
.3. A 7-month-old child “fell over” while crawling and now presents with a swollen leg. Imaging reveals a fracture of a bowed femur, secondary to minor trauma, and thin bones (see x-ray at right). Blue sclerae are also noted. At age 1 month, the infant had multiple fractures in various states of healing (right clavicle, right humerus, and right radius). A careful family history has ruled out nonaccidental trauma (child abuse) as a cause of the bone fractures. Which pairing of a defective (or deficient) molecule and the resulting pathology best fits this clinical description?
A. Elastin and emphysema
B. Fibrillin and Marfan disease
C. Type I collagen and osteogenesis imperfecta
D. Type V collagen and Ehlers-Danlos syndrome
E. Vitamin C and scurvy
Correct answer = C. The child most likely has osteogenesis imperfecta. Most cases arise from a defect in the genes encoding type I collagen. Bones in affected patients are thin, osteoporotic, often bowed, and extremely prone to fracture. Pulmonary problems are not seen in this child. Individuals with Marfan syndrome have impaired structural integrity of the skeleton, eyes, and cardiovascular system. Defects in type V collagen cause the classic form of Ehlers-Danlos syndrome characterized by skin extensibility and fragility and joint hypermobility. Scurvy caused by vitamin C deficiency is characterized by capillary fragility.
.2. What is the differential basis of the liver and lung pathology seen in α1antitrypsin deficiency?
With α1-antitrypsin (AAT) deficiency, the cirrhosis that can result is due to polymerization and retention of AAT in the liver, its site of synthesis. The alveolar damage is due to the retention-based deficiency of AAT (a serine protease inhibitor) in the lung such that elastase (a serine protease) is unopposed.
.4. How and why is proline hydroxylated in collagen?
Proline is hydroxlyated by prolyl hydroxylase, an enzyme of the endoplasmic reticulum that requires oxygen, ferrous iron, and vitamin C. Hydroxylation increases interchain hydrogen bond formation, strengthening the triple helix of collagen. Vitamin C deficiency impairs hydroxylation.
For additional ancillary materials related to this chapter, please visit thePoint.
I. OVERVIEW
Virtually all reactions in the body are mediated by enzymes, which are protein catalysts that increase the rate of reactions without being changed in the overall process. Among the many biologic reactions that are energetically possible, enzymes selectively channel reactants (called substrates) into useful pathways. Thus, enzymes direct all metabolic events. This chapter examines the nature of these catalytic molecules and their mechanisms of action.
II. NOMENCLATURE
Each enzyme is assigned two names. The first is its short, recommended name, convenient for everyday use. The second is the more complete systematic name, which is used when an enzyme must be identified without ambiguity.
A. Recommended name