schulze

• phosphorylation of tyrosine amino acids

• binding hormones and growth factors

• conserved intracellular domain for autophosphorylation and phosphorylation of substrate

• insulin receptor

  • IR-IRS-Pl3k-PDK-akt (among other)

• cytokines, chemokines, interleukins, interferons

• JAK = janus kinase

• STAT = signal transducer and activator of transkription

• ligand binding -> activates JAK -> phosphorylates receptor and STAT

• receptor binds STAT -> dimerization -> transkription regulation

Integrins

• attachement, cell-cell-interaction

• Outside-in signalin

  • fibronectin binds

  • cell polarity, proliferation, expression

• Inside-out signaling

  • talin binds

  • cell adhesion, migration, ECM assembly

• hormone binding -> receptor activation and G-protein activation

• exchange of GDP -> GTP subunits seperate

• hydrolysis GTP -> GDP reassociation

• GDP bound inactive state

• first messanger -> discriminator -> signal transducer -> amplifier -> second messanger

• Galpha S -> stimulates [cAMP]

• Galpha i -> inhbits [cAMP]

• Galpha q -> activation Phospholipase C

• Galpha 12/13 -> remodelling cytosceleton

• membrane bound

• binds alpha subunit of heteromeric G-protein

• activation/inhibition

• conversion of ATP into cAMP

hydrolysis of PIP2 -> IP3 + DAG

• cAMP -> metabolic regulation (Gluconeogenesis, Lipolysis)

• DAG -> muscle contraction, secretion, Vasobronchoconstriktion

• Pl3 -> activation of PKC

= programmed cell death

• requires a distress signal

• apoptotic bodys are phagocytosed by macrophages

• intrinsich

  • release of Cytochrome C by mitochondria

  • apoptosome formation

• extrinsic

  • DISC (death inducing signaling complex)

  • conversion of proaspase8 into caspase 8

apoptosis

= cell breaks into several apoptotic bodys

organells are still functional

necrosis

=cell membane ruptures -> release of content

no functional organell

• hydrophilic phosphate head

• hydrophobic tail

• structure, barrier, synthesis, isolator, signaling

• energy neutral transfer -> high exchange, unidirectional

• mechanism of action

  • voltage

  • ligand

  • temperature

  • mechanic

  • pH

• ion selectivity

• protein superfamily

Na+K+ATPase

• outside binding of 2 K+

• inside binding of 3 Na+

• complete binding ATPase activity

• faciliates resting membrane potential

Co-transport

• transfer only upon binding of co-substrate

• e.g. Glucose

Counter-transport

• transfer only upon binding of counter-substrate

• Ca2+

• subcutanous

  • abdominal and gluteal

  • low risk factor

• intraabdominal

  • covers inner organs

  • risk of metabolic syndrome

• high energy storage, temperature isolation, mechanic protection, endocrine organe (Leptin, Adiponectin)

• mainly lipid droplets

• new borns

  • between shoulder blades

  • around adrenal gland

• adults

  • cervical

  • supraclavicular

  • paravertebral

• increase energy expenditure, metabolizes lipids

• thermogenesis by uncoupling protein 1 (UCP1)

• lipid induced metabolic organ tissue damage

• when capacity from lipid storages are surpassed

• insulin resistance

  • fatty acids induce pro inflammatory cytokine production via NFkB pathway

  • FFA binds to toll like receptor 4

  • TNFalpha causes insulin resistance by blocking insulin signaling

  • inhibitory serine phosphorylation of IRS1/2

• transport, synthesis, degradation, excretion, movement, immune function require energy

• oxidative phosphorylation, citric acid cycle, ATP synthesis produce energy

• metabolic energy = energy food - energy lost (feces, urine,..)

TDEE = total daily energy expenditure

• resting energy expenditure = REE

  • BEE + DIT = REE

• basal energy expenditure = BEE

  • mainainance of vital body functions

• diet induced thermogenesis = DIT

  • energy required for digestion, absorption, storage

• physical activity level = PAL

  • exercise/no exercise

• indirect calorimetry (measurment of O2 consumption over time)

• direct calorimetry (measurement of heat production over time)

• hydrodensitometry

  • under water

• bioelectrical impedance analysis

• skinfold measurement

• alpha cells

  • secretion of Glucagon (elevates blood glucose level)

• beta cels

  • production of Insulin, C-peptide, Amylin

• delta cells

  • somatostatin (regulates secretion of insulin and glucagon)

• PP cells

  • pancreatic polypeptide secretion

  • regulation of pancreatic hormones

• epsilon cells

  • production of ghrelin (regulation of satiety/hunger)

• GLUT4 vesicles to membrane

• increased glycogen synthesis

• decresed gluconeogenesis

• increased lipogenesis

non alcoholic liver disease

• triglyceride accumulation in hepatocytes

• disfunctional lipoprotein synthesis

• insulin resistance

non alcoholic steatohepatitis

• in addition to NAFLD

• inflammation

• insulin resistance

• fibrosis

• Rigor complex: Myosin-Actin

• ATP binding: Myosin-ATP

• ATP hydrolysis: Myosin-ADP+Pi

• Myosin-Actin + Myosin-ADP-pi

• force generation -> Myosin-Actin

• loss f skeletal muss mass, quality and strength

• associated with aging

• accumulation of non-contractile protein aggregates

• loss of bon mineral density

• weakening of bones, fracture

• T-score

• Osteopenia, Osteoporosis, severe osteoporosis

• de novo formation and turnover of bones

• intramembranous

  • flat bones without bone marrow

• echondriale ossification

  • commited cartilage cells -> proliferating chondrocytes

  • hypertrophic chondrocytes and pre-hypertrophic chondrocytes

  • secondary ossification -> bone formation

ossification

• osteogenesis

calcification

• assimilation of calcium based crystals

osteoblasts

• bone formation

osteoclasts

• bone resorption

homeostasis

• endocrine regulation of calcium metabolism

• Parathyroid hormone -> activation osteoclasts

• Calcitonin -> inhibition of Osteoclasts