Biochemistry-Enzymes and Proteins in Clinical Diagnosis

Created by meeras89 

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Cell Damage or Abnormal Metabolism can Lead to disease

-this is often caused by insufficient enzyme activities
-enzyme deficiency can result from a genetic defect(-->abnormal AA composition which results in many defects) or from nutritional deficiency of coenzymes

Nutritional Deficiency

-can be due to:
a. lack of dietary AA for enzyme synthesis
b. lack of energy to synthesize the enzymes
c. lack of vitamins or minerals for the formation of coenzymes

Toxins

-lead to deficiency by:
a. interaction with metal cofactors
b. binding to SH group
c. irreversible inhibition by modification of active site

Myocardial Cells

-Myocardial cells must die in order for intracellular contents to be released in measurable amounts
-brief schemic episodes (angina pectoris) DN result in release of intracellular enzymes or proteins tha lead to measurable changes
-time course of elevated levels of myocardial enzymes in serum depends of rate of diffusion of enzymes through damaged tissue and lifetime of enzymes

Myocardial enzymes

1. Creatine kinase- 18 hrs of lifetime in the blood
2. Aspartate amino transferase- cytosolic is 24 hrs and mitochondrial is 1 hr
3. LDH- is 5 days (and also biggest enzyme)

Creatine Kinase

-catalyzes the reversible reaction of creatine to phosphocreatine
-has different isoenzymes (catalyze same rxn but differ in their AA comp. Often tissue specific and useful for diagnosis or the tissue type of damaged cells).
-CK is found in cytosol and mitochondria and used as an injury marker
-mainly found in heart, muscle, and brain, NOT in liver
-sCK (serum CK) is used as a marker for acute myocardial infarction, rhabdomyolysis, muscular dystrophy, acute renal failure
-CK contains two subunits: B and M
-CKBB (CK1) : found in brain, smooth intestinal muscle and DN accumulate in the serum
-CKMB (CK2): found in the highest quantity in the heart (than skeletal or smooth)
-myocardium has 30% CKMB and 70% CKMM
-during an MI: increase in serum of CKMB to more than 5% of total sCK is an indicator. CKMB and CKMM are increased in the serum. % of CKMB of total CK is indicator to severity of the damage
-Skeletal muscle has 98% CKMM and less than 1% of CKMB
-muscular dystrophy or rhabdomyolysis lead to elevated sCK MM
-CK isozymes are negatively charged and migrate toward positive anode

Early MI markers in serum

1. CK, CKMB (can be measured right after MI, but levels return to baseline two days after MI)
2. cardiac troponin 1 (cTroponin) (protein found in muscle and does not have specific isoprotein for the heart) - can even be measured days after an MI (up to 6 days after large MI) . can be measured when CKMB goes back to baseline. this is usually measured instead of LDH)
3. Myoglobin (unspecific for the heart)- can be measured also in hrs after MI
4. Serum LDH levels- not used as an early marker because they peak after two days. they can be used when CK is down to baseline.

LDH

-have subunits H and M (H4, H3M, H2M2, HM3, M4)- in heart, RBC, muscle, and liver
-it is normal that RBCs destroyed in blood and leak into serum from RBCs
-normal serum shows a low LDH1/LDH2 ratio
-but during an MI, heart LDH isozymes leak into blood (heart has high LDH1/LDH2) --> and this will be seen in blood-->increase of LDH 1 is known as the FLIP

Liver Damage

-liver damage--> hepatocytes releasing enzymes after injury. but these cells are damaged not dead.
-Liver Failure: functional liver failure DN occur until 80% of liver's capacity has been damaged beyond repair
-Liver damage seen to be severe when have increase in NH4 ions and decrease in serum albumin decreases
-liver damage due to ethanol toxicity shows serum levels AST/ALT >2. This is bc AST leaks out from hepatocytes not only from cytosol but from mitochondria too

Enzymes of the Liver

1. ALT- alanine amino transferase: cytosolic enzyme found in higher conc in liver cytosol than in other organs. Needed for gluconeogenesis.
2. AST- Aspartate Aminotrasferase: found in cytocol and mitochon and is not specific for the liver (has been used for cardiac marker in the past). Used as a liver injury marker together with other injury markers
3. ALP- Alkaline phosphatase: found in liver, bone, intestine and placenta. located on the canicular surface of the hepatocyte. Obstructive processes (cirrhosis, galstones) induce ALP to be released into serum.
4. GGT- gamma-glutamyltranspeptidase- involved in gamma-glutamyl cycle in liver and kidney (in the cytosol and cleaves and re-synthesizes glutathione during uptake of AAs). It can be induced in the liver and released into serum after high ethanol uptake OR after medical drugs.

Liver Bile Duct Obstruction

-intra-hepatic bile ducts are obstructed in patients with liver cirrhosis.
-extra-hepatic bile ducts are obstructed by gallstones or tumors
-ALP, GGT, and conjugated billirubin will be elevated in the serum

Bone Injury Marker

-sALP is also a bone injury marker for bone diseases or bone tumors
-high sALP is normal in children with growing bones or in women during pregnancy

Prostate Cancer

-PSA test: prostate specific antigen test
-for liver cancer, use alpha fetoprotein

Acute Pancreatitis

-High lipase/amylase ration is indicator for ethanol induced pancreatitis
-(serum amylase and serum lipase)

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