Skin biochem

Question 1

key properties of skin

Answer 1

6% of body weight
contains sweat glands, melanocytes and nerve endings

main protein is KERATINS (an intermediate filament)

Question 2

layers of SKIN

Answer 2

1. epidermis: keratinised stratified squamous peithelium).
2. dermis: upper loose CT and lower reticular region containing dense CT (mainly collagen + fibroblast cells)
3. hypodermis: areolar CT with adipose + blood vessels/nerves/etc.

Question 3

functions of skin (7)

Answer 3

1. thermoregulation
2. barrier for chem and phys damage
3. pathogen barrier
4. tactile sensation
5. metabolism (vitamin D synthesis)
6. antimicrobial secretions
7. endocrine function

Question 4

how do substances like drugs cross the skin

Answer 4

THROUGH PORES: they are there both for secretion (eg of sebum) AND for absorption of drugs and therapeutics

Question 5

layers of EPIDERMIS (5)

Answer 5

1. stratum basale: melanocytes, merkel cells, stem cells undergoing mitotic division
2. stratum spinosum: langherhans cells and TIGHT desmosome junctions
3. stratum granulosum: keratinocytes containing keratohyaline granules containing loricrin and profilagrin.
4. stratum lucidum: sometimes present
5. 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

Question 6

cells in the epidermis and functions (4)

Answer 6

1. keratinocytes: throughout all layers as they undergo terminal differentiation - for protection and waterproofing
2. melanocytes: SB, produces melanosome
3. merkel cells: SB, sensory nerve ending acting as mechanpreceptor
4. langerhans cell: SS, immune response

Question 7

what junctions are present in the epidermis

Answer 7

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

Question 8

skin keratins structure and function

Answer 8

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

Question 9

terminal differentiation across the layers

Answer 9

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

Question 10

brick and mortar model explanation

Answer 10

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

Question 11

what types of FAs are found in the SC

Answer 11

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

Question 12

what ions regulate the barrier function of the SC

Answer 12

CALCIUM (mainly bcs it is a secondary messenger) and also K

Question 13

what is the function of the brick and mortar SC structure

Answer 13

barrier function - against physical and chemical agents AND to prevent dehydration

Question 14

what is the structure formed below the membrane of the corneocytes at the SC

Answer 14

CORNIFIED ENVELOPE: higly cross linked insoluble proteins and extracelullar lipids.

SCAFFOLD PROTEINS: involucrin, loricrin, periplakin, envoplakin

intercellular lipid lammellae = CORNEODESMOSOMES containing desmogelin and desmocolin.

Question 15

what ion controls the cornified envelope structure

Answer 15

Ca2+ –> an increase in calcium upregulates the assembly of the CE

Question 16

production of filagrin

Answer 16

1. produced as profilaggrin and stored in keratohyaline granules in SG
2. cleaved into monomers via proteases which bind to keratins and IFs.
3. This forms the FLG-K bundle present in the corneocytes

Question 17

degradation of filagrin

Answer 17

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

Question 18

loricrin role

Answer 18

present in keratohyaline granules in the SG
-released to become a scaffold protein in the CE: it cross links to involucrin via transglutaminase

Question 19

role of transglutaminase

Answer 19

cross links loricrin to involucrin to form the CE

!! they are calcium ion dependent

Question 20

what are the contents of the lamellar bodies in keratinocytes

Answer 20

1:1:1 ratio of ceramide cholesterol and free FAs

Question 21

cermide sythesis and role

Answer 21

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

Question 22

what does the quality of lipids of the brick and mortar layer determine

Answer 22

permeability of the skin

Question 23

skin pH control

Answer 23

ACIDIC: 5.2-5.7
controlled by several sources of H+:
-free FAs
-lactic acid in sweat
-Na+/H+ antiporters
-melanin and flaggrin pathways

Question 24

why is pH maintenance important

Answer 24

1. allows balance between microorganism of the skin vs pathogenic organisms from the outside
2. optimum pH for cermanide synthesising enzymes is acidic
3. general regulation of epidermal differentiation and desquamation

Question 25

endocrine function of skin

Answer 25

steroid hormone synthesis from precursors (bcos of the presence of cholesterol):

ACTH, CRH glucocorticoids and cytokines

Question 26

sense receptors present in the skin

Answer 26

MECHANORECEPTORS: merkel cells, pacinian/ rufinni and meissner’s corpuscles

TRPV: thermoreceptor channels which open and close in response to temperature

Question 27

what compounds are responsible for the colour of the skin

Answer 27

1. melanin (2 types)
2. Hb (in blood vessels of the dermis)
3. carotene (yellow pigment)

Question 28

melanin types

Answer 28

1. EUMELANIN: brown/ black, highly protective to UV
2. PHEOMELANIN: red/ blone form, UV permeable

Question 29

how do melanocytes exert their function

Answer 29

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).

Question 30

synthesis of eu and pheo melanin + regulation

Answer 30

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)

Question 31

UV penetration through skin layres

Answer 31

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.