MARKERI BIOCHIMICI, IMUNOLOGICI I GENETICI, N PATOLOGIE

Markeri biochimici
- lactat dehidrogenaza - copil 60-170 U/L; adult 100-190 U/L
- LDH1 - infarct
- LDH5 - afeciuni musculare, efort fizic, citoliz hepatic
- AST (GOT), ALT (GPT) - AST - 10-50 U/L; ALT - 4-36 U/L
- infecii virale hepatice, ALT persist mai mult
- AST - efort muscular intens, infarct miocardic, distrofie
muscular
- CPK (CK) - afeciuni musculare, miozit, hipertermie malign, leziuni musculare
- BB - leziuni cerebrale, neurochirurgie
- MM, MB - afeciuni miocardice, transplant cardiac
- foafataza alcalin - obstrucia cilor biliare, afeciuni osoase, cancer osos

- amilaza - pancreatit acut, traumatisme abdominale, radiografie abdominal

- lipaza - pancreatita acut
- G-6-P-DH-aza - anemie hemolitic
- anemie megaloblastic, hepatit viral
- aldolaza - 1,5-8,1 U/L
- injecii intramusculare, distrofie muscular, infarct miocardic
- atrofie muscular
- gama-GT - 5-27 U/L - hipotiroidism
- - hepatit, ciroz, colestaz, alcoolism, pancreatit

Markeri imunologici
- anticorpi antifosfolipidici (anticardiolipin) - negativ
- lupus, sindrom antifosfolipidic, avort spontan, sifilis
- anticorpi anticelul parietal - negativ
- anemie pernicioas, gastrit atrofic
- anticorpi antigliadin - Ig A/Ig G antigliadin < 20 EU
- boala celiac
- anticorpi anti-insulin - negativ
- diabet zaharat insulinorezistent
- ASLO - < 160 U/L
- infecie streptococic, RAA, glomerulonefrita acut
- factorul reumatoid - < 60 U/mL
- poliartrita reumatoid
- antigen H. pylori - negativ
- anticorpi anti-hepatitici - anti-HVA, antigenul HBs, anticorpi anti-HBs, anticorpi
anti-HCV

Markeri genetici
- sunt utilizai pentru:
- evidenierea afeciunilor genetice
- stabilirea cauzelor apariiei afeciunii genetice
- stabilirea riscului de transmitere a afeciunilor la descendeni - cancer, diabet
- analiza - materialulului genetic
- proteine, enzime

BIOCHIMIA STRESULUI OXIDATIV

Stresul oxidativ - dezechilibru balanei prooxidant/antioxidant
Radical liber - orice atom sau molecul care conine unul sau mai muli electroni
nepereche care intensific reactivitatea chimic a atomului sau moleculei

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

Inactivarea radicalilor liberi radicalilor liberi

- vitamine i substane naturale antioxidante - caroteni, vitaminele A, E, C;
flavonoide, licopen, acizi -3
- enzime antioxidante - catalaza, SOD
- compui endogeni cu aciune antioxidant - glutation, compui tiolici, acid uric,
metalotioneine

BIOCHIMIA INFLAMAIEI

- PL-aza A2 - inh. corticosteroizi

- COX 1, 2,3 - inh. AINS

MECANISME BIOCHIMICE N BOLILE NEURODEGENERATIVE

- mutaii genetice - afectarea sintezei i a realizrii structurii secundare, teriare i

cuaternare a proteinelor
- acumulare intracelular de proteine toxice - boala Huntington,
- stres oxidativ - scleroza lateral amiotrofic, Alzheimer
- dezechlibru ntre mediatori - boala Parkinson
- dezechilibru vitaminic - Alzheimer
- apoptoz neuronal

ENZIMOPATII
Metabolismul glucidic
- glucozo-6-P-DH-aza - anemie hemolitic, methemoglobinemie, infecii
- transcetolaza tulburri neurologice, comportamentale (sd. Wernicke-Korsakoff)
- glicogenoze
- deficit de galactokinaz
- deficit de lactz, trehalaz

Metabolismul proteic
- deficiene enzimatice n ciclul ureei - hiperamonemie
- fenilalaninhidroxilaza - fenilcetonurie
- homogentizic oxidaza - alcaptonurie
- tirozinaza - tirozinemie
- enzime pentru sinteza hemului - porfirii

Metabolismul lipidic
- lipaza pancreatic - steatoree
- glucocerebrozidaz - boala Gaucher
- hexozaminidaz A - boala Tay-Sachs

- sfingomielinaza lizozomal - boala Nieman-Pick A, B, C, D

MECANISME BIOCHIMICE N GERONTOPATOLOGIE

1. Stres oxidativ - producerea de compui cu aczivitate oxidant intens

2. Excesul de alimente
3. Suprastimularea axei hipotalamo-hipofizo-corticosuprarenal
4. Apoptoz celular
5. Stimularea proceselor inflamatorii

Bibliografie selectiv
Beckman K.B., Ames B.N. The free radical theory of aging matures, Physiol Rev 1998; 78: 547-572.
Burtis C.A.., Ashwood E.R. Tietz Textbook of Clinical Biochemistry, Third Edition, W.B. Saunders Company, Philadelphia,
1999.
de Diego-Otero Y., Romero-Zerbo Y., el Bekay R. Et al. Alpha-tocopherol protects against oxidative stress in the fragile X
knockout mouse: an experimental therapeutic approach for the Fmr1 deficiency. Neuropsychopharmacology 2009; 34 (4):
10111026.
Dejica D. Stresul oxidative n bolile interne, Ed. Casa Crii de tiin, Cluj-Napoca, 2000.
Ksiazek K., Passos J.F., Olijslagers S., von Zglinicki T. Mitochondrial dysfunction is a possible cause of accelerated
senescence of mesothelial cells exposed to high glucose. Biochemical and Biophysical Research Communications 2008; 366:
793-799.
Lin M.T., Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443 (7113):
787-795.
Messner K.R., Imlay J.A. Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate
dehydrogenase, and aspartate oxidase. J. Biol. Chem. 277 (45): 42563-42571.
Mitteldorf J., Pepper J. Senescence as an adaptation to limit the spread of disease. Journal of Theoretical Biology 2009; 260:
186-195.
Murgia C., Pritchard J.K., Kim S.Y., Fassati A., Weiss R.A. Clonal origin and evolution of a transmissible cancer. Cell. 2006;
126 (3): 477-487.
Seaver L.C., Imlay J.A. Are respiratory enzymes the primary sources of intracellular hydrogen peroxide? J. Biol. Chem. 2004;
279 (47): 48742-48750.
Valko M., Morris H., Cronin M.T. Metals, toxicity and oxidative stress. Curr. Med. Chem. 2005; 12 (10): 1161-1208.
Zdanov S., Bernard D., Debacq-Chainiaux F., Martien S. et al. Normal or stress-induced fibroblast senescence involves COX-2
activity. Experimental Cell Research 2007; 313: 3046-3056.
Wenk G.L. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2003; 64 (Suppl 9): 7-10.