ENZIME.

EFECTORI ENZIMATICI
- proteine sintetizate n celule; catalizeaz reacii biochimice

Structura enzimelor
- proteine simple
- heteroproteine partea proteic apoprotein (apoenzim)
specificitate de substrat
- partea neproteic cofactor aciunea catalitic
- organic (coenzim, grupare prostetic),
- anorganic (ioni metalici)

- nucleoproteine
Clasificarea enzimelor
- dup sistemul IUBMB
1. Oxidoreductaze - dehidrogenaze, oxidaze, oxigenaze, hidroperoxidaze
2. Transferaze - aminotransferaze, kinaze, glicoziltransferaze, metiltransferaze
3. Hidrolaze - fosfataze, proteaze, fosfolipaze, tiolaze, lipaze
4. Liaze - decarboxilaze, dehidraze,
5. Izomeraze - epimeraze, mutaze
6. Ligaze
 Aplicaiile enzimelor n medicin i farmacie

1. Reactivi analitici
- dozarea medicamentelor - tehnica ELISA
- dozarea compuilor endogeni - glucoza, uree, acid uric
- dozarea unor compui exogeni alcool
2. Ageni terapeutici
- streptokinaza, urokinaza
- reptilaza
- hialuronidaza
- asparaginaza
- enzime proteolitice tripsina, chimotripsina
- PEG-adenozin deaminaza (Adagen)

3. Indicatori paraclinici
- cantitatea eliberat depinde de - gradul afectrii celulare
- concentraia intracelular a enzimei
- masa de esut afectat
- inactivare/eliminare din ser - denaturare
- separarea de coenzim/metal
- inhibitori plasmatici
- distrugere de ctre proteaze
- eliminare renal
3. Indicatori paraclinici
- lactat dehidrogenaza - copil 60-170 U/L; adult 100-190 U/L
- LDH1 - infarct miocardic
- LDH5 - afeciuni musculare, efort fizic, citoliz hepatic
- AST (GOT; 10-50 U/L), ALT (GPT; 4-36 U/L)
- cresc n infecii virale hepatice; ALT persist mai mult
- infarct miocardic, distrofie muscular, efort muscular intens AST
- gama-GT - hipotiroidism
- - hepatit, ciroz, colestaz, alcoolism, pancreatit
- CPK (CK) - copii
- MM i MB - afeciuni miocardice, transplant, hipertermie malign
- BB - leziuni cerebrale, neurochirurgie
3. Indicatori paraclinici
- fosfataza alcalin - - obstrucia cilor biliare, colestaz, hepatit,
afeciuni ale oaselor, acromegalie; sarcin

- fosfataza acid afeciuni ale prostatei

- amilaza
- pancreatita acut, traumatisme abdominale, radiografie abdominal

- lipaza - pancreatita acut

- glu-6-P-DH-aza - anemie hemolitic

- anemie megaloblastic, hepatit viral
 OXIDAREA BIOLOGIC.
BIOTRANSFORMAREA XENOBIOTICELOR

Oxidarea - sub aciunea oxido-reductazelor

- grupate n 23 de subclase n funcie de natura substratului donor sau acceptor
de H i e-
- n funcie de prezena sau absena oxigenului - aerob
- anaerob
Oxidoreductaze
EC 1.1. Oxidoreductaze care acioneaz asupra substraturilor care conin gruparea
CH-OH
EC 1.2. Oxidoreductaze care acioneaz asupra substraturilor cu grupare carbonilic
EC 1.3. Oxidoreductaze care acioneaz asupra legturii CH-CH din substrat
EC 1.4. Oxidoreductaze care acioneaz asupra substraturilor care conin gruparea
-CH-NH2
EC 1.5. Oxidoreductaze care acioneaz asupra substraturilor care conin gruparea
-CH-NH-
EC 1.6. Oxidoreductaze care utilizeaz NADH sau NADPH ca donori de H i electroni
EC 1.7. Oxidoreductaze care utilizeaz compui cu azot ca donori de H i electroni
EC 1.8. Oxidoreductaze care utilizeaz compui cu sulf ca donori de H i electroni
EC 1.9. Oxidoreductaze care utilizeaz hemul ca donor de electroni
EC 1.10. Oxidoreductaze care utilizeaz difenolii ca donori de H i electroni
EC 1.11. Oxidoreductaze care utilizeaz peroxidul de hidrogen ca donor de H i
electroni
EC 1.12. Oxidoreductaze care utilizeaz hidrogenul ca agent reductor
EC 1.13. Oxidoreductaze care utilizeaz un singur agent reductor pentru reducerea O2
EC 1.14. Oxidoreductaze care utilizeaz o pereche de ageni reductori pentru
reducerea O2
EC 1.15. Oxidoreductaze care catalizeaz reacii n care superoxidul este acceptor de
echivaleni reductori
EC 1.16. Oxidoreductaze care catalizeaz reacii de oxidare a ionilor metalici
EC 1.17. Oxidoreductaze care catalizeaz oxidarea unor grupe CH sau CH2
EC 1.18. Oxidoreductaze care utilizeaz proteinele cu Fe i S ca donori de echivaleni
reductori
EC 1.19. Oxidoreductaze care utilizeaz flavodoxina ca donor de echivaleni redctori
EC 1.20. Oxidoreductaze care catalizeaz oxidarea fosfonailor i arseniilor
EC 1.21. Enzime care acioneaz oxidativ asupra compuilor de tip X-H i Y-H cu
formarea compuilor de tip X-Y
EC 1.22. Oxidoreductaze care utilizeaz derivai halogenai ca ageni reductori
EC 1.97. Alte oxidoreductaze
Biotransformarea xenobioticelor
- reacii din faza I - oxidare
- reducere
- hidroliz
- reacii din faza a II-a - conjugare cu compui endogeni
- acid glucuronic, sulfat, cistein, glutation, glicocol, acetat
 BIOCHIMIA RADICALILOR LIBERI

Sinteza radicalilor liberi

1. iniiere are loc scindarea unui compus
2. propagare radicalul liber reacioneaz cu un atom sau o molecul i determin
apariia unor noi radicali liberi
3. finalizare radicalii liberi reacioneaz cu biomolecule pe care le afecteaz

Surse de radicali liberi:

- exogene expunerea la radiaii UV, oxidani, hipoxie,
- endogene n cursul reaciilor oxidative din mitocondrie, peroxizomi, lizozomi
Radicali liberi i specii reactive ale oxigenului
- anionul superoxid
- radicalul hidroxil - HO
- radicalul hidroperoxil - HO2
- radicalul peroxil - RO2
- radicalul alcoxil - R-O
- peroxidul de hidrogen - H2O2
- specii reactive din azot - peroxinitrit
- acidul hipocloros

Efectele negative ale radicalilor liberi

- afectare cerebral
- diabet
- ateroscleroz
- boli autoimune
- carcinogenez
 BIOCHIMIA ACIDULUI ARAHIDONIC
MEDIATORI BIOCHIMICI N INFLAMAIE I N REACIILE ALERGICE

acid arahidonic
(C20:4), -6
 BIOCHIMIA UNOR OLIGO- I POLIPEPTIDE BIOLOGIC ACTIVE

Hormoni
- hipofiz - STH, ACTH, prolactina, TSH, FSH, LH, ADH, oxitocina
- tiroida - calcitonina
- paratiroide - PTH
- pancreas - insulina, glucagon

GRELINA
hormonul foamei
- 28 aa +/- n-octanoil
- sintez - stomac, intestin, cel. pancreatice, testicule
- efort fizic, obezitate [grelina]
- stres psihic - expresia genelor pt. Grelin
- ingestia de alimente de 4-6 ori, secr. i motilitatea gastric
- riscul de ateroscleroz
OBESTATINA
- sintez - stomac, IS, pancreas, splin, glanda mamar
- activare - amidare - COOH terminal
- obezi - [obestatina]

OREXINA A i B
- sintez - aria hipotalamic lateral
- aciune - ingestia de alimente

LEPTINA
- sintez - adipocite, cerebral
- ingestia de alimente
- dezvoltarea esutului adipos
NEUROPEPTIDE
- Y - antiepileptic, efecte GABA-ergice
- S - anti-nociceptiv

- i -DEFENSINA
- secreie - celule mucoasa bronic, epiteliu, neutrofile
- aciune - - antimicrobian, chemotaxie
- - inhib fibrinoliza
 BIOCHIMIA SENESCENEI
Mecanisme biochimice - stres oxidativ
- exces de glucide n alimentaie
- stimularea axei hipotalamo-hipofizo-corticosuprarenale
- apoptoza celular
- procese inflamatorii
Mecanisme genetice - afectarea transcripiei genice
- gena mbtrnirii
- scurtarea telomerilor
- activarea oncogenelor

Indicatori paraclinici pentru evaluarea procesului de senescen

Progeria

Prevenirea i reducerea ritmului senescenei

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