Elastin Metabolism and Composition

ATP7A Gene and Related Conditions

• ATP7A gene provides instructions for making a copper-transporting ATPase, essential for copper homeostasis.
• Autosomal recessive forms of cutis laxa often present with more severe manifestations compared to the milder autosomal dominant forms.
• The X-linked form of cutis laxa is often referred to as "X-linked cutis laxa."

Supravalvular Aortic Stenosis (SVAS)

• The gene associated with causing Supravalvular aortic stenosis is ELN (elastin gene).
• Aortic narrowing due to SVAS can lead to increased pressure in the heart, potentially causing heart failure.

Menkes Syndrome and Melanin

• A mild type of Menkes syndrome is known as "occipital horn syndrome."
• Pheomelanin is a pigment in the skin that resembles melanin and is diffusely located throughout the epidermis.
• Eumelanin is composed of a polymer of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA).

Hair and Freckles

• Pheomelanin is largely responsible for red hair and freckles.
• The precursor of melanin synthesis is tyrosine.
• The organ affected by melanin synthesis is primarily the skin.

Hemoglobin and Elastin

• Hemoglobin has a characteristic red color.
• Elastin has an estimated half-life of about 70 years in the human body.
• There are two tropoelastin genes in humans which encode the precursor of elastin.

Elastin and Connective Tissue Disorders

• The enzyme lysyl oxidase catalyzes the reaction that links soluble tropoelastin proteins to form elastin.
• Ehlers-Danlos syndrome is characterized by loose, sagging skin, a risk of aneurysm, and emphysema.
• Lysyl oxidase's main role in elastin metabolism is to facilitate the cross-linking of collagen and elastin fibers.

Genetic Disorders and Connective Tissue Abnormalities

• Williams syndrome is associated with a genetic pattern of deletion in the 7q11.23 region.
• The gene associated with Williams syndrome is the ELN gene (elastin).
• Connective tissue abnormalities in Williams syndrome are due to the disruption of elastin production.

Marfan Syndrome

• The gene responsible for encoding fibrillin-1 protein in Marfan syndrome is the FBN1 gene.
• The Fibrillin-1 protein plays a crucial role in maintaining connective tissue integrity and elasticity.
• Marfan syndrome is characterized by unusual tall stature, long limbs, and thin fingers.

DNA Repair and Skin Cancer

• In the excision repair process, the likelihood that the replacement base is the same as the removed base is quite low.
• Excision repair can significantly lower the risk of developing skin cancer by repairing DNA damage caused by UV radiation.
• Melanin's role includes protecting the skin from UV rays by absorbing and dissipating harmful radiation.

UV Radiation and Natural Skin Color

• The photochemical process that converts UV-photon energy into heat is known as "thermalization."
• If UV-photon energy is not converted into heat, it can result in DNA damage, leading to skin aging or cancer.
• Individuals with darker natural skin color have enhanced photoprotection due to higher melanin concentrations, which absorb more UV radiation.