Sec 11 Disorders of Melanocytes Flashcards
Ratio of melanocyte to keratinocytes
1:5-6
Pigmented polymer that is stored in cytosolic organelles
Melanin
Cytosolic organelles that are transferred to keratinocytes through melanocyte dendritic processes
Melanosomes
Describes a single epidermal melanocyte surrounded by several epidermal keratinocytes
Epidermal melanin unit
Major differentiated function of melanocytes
To synthesize melanin in specialized organelles within the melanocytes, the melanosomes, and to transfer melanosomes to neighboring keratinocytes in order to provide protection from UV irradiation
Are large (∼0.9 × 0.3 mm), elliptical in shape and contain a highly structured fibrillar glycoprotein matrix required for eumelanin synthesis.
Eumelanosomes
Are smaller (∼0.7 mm in diameter), spherical in shape and their glycoprotein matrix appears disorganized and loose
Pheomelanosomes
Dark, brown–black, and insoluble melanin
Eumelanin
Light, red–yellow sulfur-containing, and soluble melanin
Pheomelanin
Critical rate-limiting step in melanogenesis
Conversion of tyrosine to DOPA
The main function of melanin
To provide protection against UV-induced DNA damage by absorbing and scattering UV radiation (280–400 nm).
These proteins act as short cross-bridge structures connecting the organelle to the microtubules.
Kinesins (centrifugal, anterograde)
Dyneins (centripetal)
Potent stimulators of melanogenesis
MSH and ACTH
A diffusible free radical displaying pleiotropic bioregulatory effects in diverse cells and tissues which are produced by melanocytes and keratinocytes in response to inflammatory cytokines. Its production in keratinocytes is induced by UV irradiation increasing tyrosinase activity and melanogenesis
Nitric Oxide
A group of signaling molecules, primarily functioning as neurotransmitters and as endocrine hormones
Catecholamines
Most common inherited disorder of generalized hypopigmentation, with an estimated frequency of 1 in 20,000 in most populations.
Oculocutaneous albinism (OCA)
Results from the dysfunction of a normal complement of pigment cells, which results in complete or partial loss of cutaneous pigmentation.
Albinism
Caused by loss of function of the melanocytic enzyme tyrosinase resulting from mutations of the TYR gene. Most common type in non-Hispanic Caucasian patients.
OCA1
There is a complete inability to synthesize melanin in skin, hair, and eyes, resulting in the characteristic “albino” phenotype. They are born with white hair and skin and blue eyes, and there are no changes as they mature. The hair may develop a slight yellow tint due to denaturing of the hair protein due to sun exposure and/or shampoo use. The irides are translucent, appear pink early in life, and often turn a gray–blue color with time. No pigmented lesions develop in the skin.
OCA1A
Can range from minimal hair pigment to skin and hair pigmentation approaching the normal pigmentary phenotype for the individual’s genetic composition and continental ancestry. Most have very little or no pigment at birth and develop varying amounts of melanin in the hair and skin in the first or second decade of life. The hair color changes to light yellow, light blond, or golden blond first, as a result of residual pheomelanin synthesis, and eventually can turn dark blond or brown in adolescents and adults. The irides can develop light-tan or brown pigment, sometimes limited to the inner third of the iris, and iris pigment can be present on globe transillumination. Many individuals will tan with sun exposure. Pigmented lesions (nevi, freckles, lentigines) develop in the skin of individuals who have developed pigmented hair and skin.
OCA1B
Due to mutations of the P gene, which maps to chromosome arm 15q
OCA2
Hair is yellow at birth and remains so throughout life, although the color may turn darker. The skin is creamy white at birth and changes little with time. No generalized skin pigment is present, and no tan develops with sun exposure, but pigmented nevi, lentigines, and freckles often develop, since the cutaneous melanocytes in these individuals both remain susceptible to ultraviolet (UV)induced changes early in life and retain some ability to synthesize melanin later. The irides are blue–gray or light tan or brown.
OCA2
Due to mutations in the TYRP1 gene
OCA3
Distinct OCA phenotype in which the skin color is a mahogany brown with a slight reddish hue, and the hair color varies from deep mahogany to sandy red.
Rufous OCA