Human Physiology, 14th edition (2016)

668 Chapter 19

Clinical Investigation CLUES

Marty took a topical psoriasis medicine that contained a

vitamin D derivative, and the physician mentioned that

vitamin D supplements could also help prevent bone

loss.

• By what mechanisms does vitamin D affect bones?


• By what mechanisms might vitamin D help treat
  Marty’s psoriasis?

Figure 19.1 Reactive oxygen species (ROS) production and defense. Normal physiology requires that the reactive
oxygen species (those that contain oxygen with an unpaired electron) be kept in balance.

• Cell death


• Diseases


• Aging

Excessive ROS Inadequate ROS

If

If

• Impaired immune function


• Impaired cell proliferation


• Other impaired responses

Exogenous

causes of ROS

production

Antioxidant

defenses

• Mitochondria


• Peroxisomes


• NADPH
  oxidase


• Other
  enzymes


• Inflammatory
  cytokines

Normal

physiology

Endogenous

sources of ROS

• Ultraviolet light


• Ionizing radiation


• Drugs


• Environmental
  toxins
  
  
  • Enzymes (catalase,
    superoxide
    dismutase, and
    glutathione
    peroxidase)
  
  
  • Glutathione
  
  
  • Vitamins A, C, and E
  
  
  • Other antioxidants
  
  
  
  

vitamin D have overlapping functions—all three are involved in
regulating gene expression and promoting differentiation (spe-
cialization) of tissues.

Minerals (Elements)

Minerals (elements) are needed as cofactors for specific enzymes
and for a wide variety of other critical functions. Those that are
required daily in relatively large amounts include sodium, potas-
sium, magnesium, calcium, phosphorus, and chlorine (see
table  19.2 ). In addition, the following trace elements are recog-
nized as essential: iron, zinc, manganese, fluorine, copper, molyb-
denum, chromium, and selenium. The trace elements are required
in much lower daily doses than the previously mentioned elements
(minerals; table 19.2 ).

Free Radicals and Antioxidants

The electrons in an atom are located in orbitals, with each
orbital containing a maximum of two electrons. When an
orbital has an unpaired electron, the molecule containing the
unpaired electron is called a free radical. Free radicals are
highly reactive in the body, oxidizing (removing an electron

from) other atoms, or sometimes reducing (donating their

electron to) other atoms. The major free radicals are referred

to as reactive oxygen species if they contain oxygen with an

unpaired electron, or reactive nitrogen species if they contain

nitrogen with an unpaired electron. Mitochondria are a major

source of reactive oxygen species, produced by the electron

transport chain as a byproduct of aerobic respiration (chapter 5,

section 5.2). Although most electrons reach the third pump of

the electron transport system (see fig. 5.9), about 1% to 3%

react with oxygen prematurely to form the superoxide radical.

The unpaired electron is symbolized with a dot superscript.

Thus, reactive oxygen species include the superoxide radical

( O • 2 ), the hydroxyl radical ( HO • ), and others. Reactive nitro-

gen species include the nitric oxide radical ( NO • ) and others.

These free radicals are produced by many cells in the body and

serve some important physiological functions. The superoxide

radical and nitric oxide radical produced in phagocytic cells

such as neutrophils and macrophages, for example, help these

cells destroy bacteria. The superoxide radicals in phagocytic

cells can be thought of as nonselective antibiotics, killing any

infecting bacteria (as well as the neutrophils) and perhaps also

injuring surrounding tissue cells, as these radicals contribute to

the inflammation reaction. In addition, the superoxide radicals

promote cellular proliferation (mitotic division) of fibroblasts,

so that scar tissue can form. The superoxide radicals have simi-

larly been shown to stimulate proliferation of lymphocytes in

the process of clone production (chapter 15). The nitric oxide

radical also has physiological actions, promoting relaxation of

vascular smooth muscle and thus vasodilation (chapter 14), so

that more blood can flow to the site of the inflammation. Thus,

free radicals do serve useful physiological roles in the body

( fig. 19.1 ).

Excessive production of free radicals, however, can damage

lipids, proteins, and DNA, and by this means exert an oxidative

stress on the body. Oxidative stress has wide-ranging ill effects

( fig. 19.1 ). It promotes cell death (apoptosis), contributes to aging