Skin biochem Flashcards
key properties of skin
6% of body weight
contains sweat glands, melanocytes and nerve endings
main protein is KERATINS (an intermediate filament)
layers of SKIN
- epidermis: keratinised stratified squamous peithelium).
- dermis: upper loose CT and lower reticular region containing dense CT (mainly collagen + fibroblast cells)
- hypodermis: areolar CT with adipose + blood vessels/nerves/etc.
functions of skin (7)
- thermoregulation
- barrier for chem and phys damage
- pathogen barrier
- tactile sensation
- metabolism (vitamin D synthesis)
- antimicrobial secretions
- endocrine function
how do substances like drugs cross the skin
THROUGH PORES: they are there both for secretion (eg of sebum) AND for absorption of drugs and therapeutics
layers of EPIDERMIS (5)
- stratum basale: melanocytes, merkel cells, stem cells undergoing mitotic division
- stratum spinosum: langherhans cells and TIGHT desmosome junctions
- stratum granulosum: keratinocytes containing keratohyaline granules containing loricrin and profilagrin.
- stratum lucidum: sometimes present
- stratum corneum: brick and mortar structure (between corneocytes and lipids), superficial layer of terminal keratinocytes is continuously shed off, cells are dead (no organelles) BUT are metabolically active
cells in the epidermis and functions (4)
- keratinocytes: throughout all layers as they undergo terminal differentiation - for protection and waterproofing
- melanocytes: SB, produces melanosome
- merkel cells: SB, sensory nerve ending acting as mechanpreceptor
- langerhans cell: SS, immune response
what junctions are present in the epidermis
DESMOSOMES (connect cell cytoskeleton to keratins AND HEMIDESMOSOMES (adhere cells to the basal lamina)
-intracellular proteins = cadherins which connect with the keratins
-desmoplakin, desmogleins and laminins
skin keratins structure and function
INTERMEDIATE FILAMENT: two types, one is acidic and the other neutral basic,
These 2 types form dimers, then tetramers, octamers, protofilaments and filaments.
-contain disuflide bonds and cross links
FUNCTION: provide structural resilience against mechanical stress
terminal differentiation across the layers
SB: proliferation and mitotic division of keratinocytes. Keratins 5/14
SS: transglutaminase (cross linking), keratins 1/10
SG: keratohyaline granules and lamellar bodies in the keratinocyte cells
SC: terminal keratinocytes (no organelles), lipid secretion by lamellar bodies to form brick and mortar model, desquamation
brick and mortar model explanation
Brick = corneyocytes
Mortar = lipids
-corneocytes replace keratinocytes –> they retain the keratin within a flagrin matrix, and the plasma membrane of the KCs is relplaces by the cornified lipid envelope with lipids secreted by lamellar bodies (forming the mortar)
-corneocytes are attached with tight corneodesmosomes
-contains a 1:1:1 molar ratio of ceramide, cholesterol and free FAs
what types of FAs are found in the SC
Mainly saturated and long (to make the packed configuration of the brick and mortar without kinks)
BUT there are a few unsaturated ones for the role of the skin as hormone producing
what ions regulate the barrier function of the SC
CALCIUM (mainly bcs it is a secondary messenger) and also K
what is the function of the brick and mortar SC structure
barrier function - against physical and chemical agents AND to prevent dehydration
what is the structure formed below the membrane of the corneocytes at the SC
CORNIFIED ENVELOPE: higly cross linked insoluble proteins and extracelullar lipids.
SCAFFOLD PROTEINS: involucrin, loricrin, periplakin, envoplakin
intercellular lipid lammellae = CORNEODESMOSOMES containing desmogelin and desmocolin.
what ion controls the cornified envelope structure
Ca2+ –> an increase in calcium upregulates the assembly of the CE
production of filagrin
- produced as profilaggrin and stored in keratohyaline granules in SG
- cleaved into monomers via proteases which bind to keratins and IFs.
- This forms the FLG-K bundle present in the corneocytes
degradation of filagrin
Degraded from the FLG-K bundles in corneocytes
this releases free amino acids –> UCAs and PCAa. These are important UV absorbing aa and maintain skin pH
loricrin role
present in keratohyaline granules in the SG
-released to become a scaffold protein in the CE: it cross links to involucrin via transglutaminase
role of transglutaminase
cross links loricrin to involucrin to form the CE
!! they are calcium ion dependent
what are the contents of the lamellar bodies in keratinocytes
1:1:1 ratio of ceramide cholesterol and free FAs
cermide sythesis and role
de novo synthesis starting in ER from 16C palmitoyl coA.
ROLE: precursor of sphingolipids, forms part of brick and mortar bcos it is present in the lipid ECM
what does the quality of lipids of the brick and mortar layer determine
permeability of the skin
skin pH control
ACIDIC: 5.2-5.7
controlled by several sources of H+:
-free FAs
-lactic acid in sweat
-Na+/H+ antiporters
-melanin and flaggrin pathways
why is pH maintenance important
- allows balance between microorganism of the skin vs pathogenic organisms from the outside
- optimum pH for cermanide synthesising enzymes is acidic
- general regulation of epidermal differentiation and desquamation
endocrine function of skin
steroid hormone synthesis from precursors (bcos of the presence of cholesterol):
ACTH, CRH glucocorticoids and cytokines
sense receptors present in the skin
MECHANORECEPTORS: merkel cells, pacinian/ rufinni and meissner’s corpuscles
TRPV: thermoreceptor channels which open and close in response to temperature
what compounds are responsible for the colour of the skin
- melanin (2 types)
- Hb (in blood vessels of the dermis)
- carotene (yellow pigment)
melanin types
- EUMELANIN: brown/ black, highly protective to UV
- PHEOMELANIN: red/ blone form, UV permeable
how do melanocytes exert their function
found in SB, release melanosome. This is transfered to keratinocytes and as they terminally differentiate they move to superior layers where melanosome is exposed to UV and becomes melanin (providing colour).
synthesis of eu and pheo melanin + regulation
synthesised within melanosomes of melanocytes –> driven by 2 main pathways: POMC and CAMP activated cascades. Tyrosinase also allows synthesis from phenylanine
Upregulated by: TFs (like MITF), MSH (melanin stimulating hormone)
UV penetration through skin layres
there are many diff types of UV radiation (A,B,C) and some are stopped by keratinocytes / CT but other are FULLY able to pass through it. Thats why protection is needed to prevent burns or mutations that cause cancer.
