315 Proteins and heme derivatives

amino acids are made up of:

carboxyl group, amino group, hydrogen, r group

essential amino acids

MUST come from diet

nonessential amino acids

can be synthesized from self

protein basic structure:

made up of C,H,N,O and sometimes S

proteins are:

polymers of amino acids linked by peptide bonds

primary protein structure:

order of amino acids in chain

secondary protein structure:

local shapes within chain (alpha helix, beta pleats)

tertiary protein structure:

3d shape of protein

quaternary protein structure:

multiple protein chains form working protein

is ionizable means:

can hold or release protons (resists changes in pH)

isoelectric point pI:

pH where protein has NO net charge

below pI:

protein positively charged (protonated)

above pI:

protein negatively charges (deprotonated)

Isoelectric focussing (IEF)

used in lab to separate proteins by pI

henderson hasselbach:

pH = pka + log (conj. base)/(conj. acid)

protein synthesis step 1:

transcription in nucleus : DNA - pre mRNA - mRNA

protein synthesis step 2:

translation in cytoplasm: mRNA codons read by ribosomes then tRNA beings a.a. then polypeptide chain forms

plasma proteins are synthesized in the:

liver

Albumin known as

major plasma protein

plasma proteins consist of:

prealbumin, albumin, globulins

prealbumin (transthyretin) function:

transports thyroxins and retinol (vitamin A)

prealbumin decreases in:

malnutrition, liver disease, inflammation (negative acute phase reaction)

prealbumin increases in:

steroid therapy, chronic renal failure

prealbumin key facts:

Transports thyroxine & retinol (vitamin A). Starvation marker. ↓ in malnutrition, liver disease, inflammation (negative acute phase). ↑ in steroid therapy, chronic renal failure.

most abundant plasma protein?

albumin

functions of albumin?

maintains colloid osmotic pressure, carrier protein, acts as an acid-base buffer

is albumin a positive or negative acute phase reactant?

negative acute phase reactant

what is the main cause hyperalbuminemia?

rare, usually due to dehydration (increases bc not enough water)

what conditions cause hypoalbuminemia?

liver disease, nephrotic syndrome, malnutrition, malabsorption

Why is albumin important in drug dosing?

Most drugs bind to albumin, so low albumin alters free drug levels and dosing.

How is albumin measured in the lab?

Using bromocresol green or bromocresol purple dye binding with spectrophotometry.

Albumin – key facts?

Most abundant plasma protein; maintains osmotic pressure, carrier, buffer; negative APR; ↓ in liver disease, nephrotic syndrome, malnutrition, malabsorption; ↑ rare (dehydration); binds drugs; measured by bromocresol dye + spectrophotometry.

What separates albumin and globulins in the lab?

Serum protein electrophoresis (SPE).

What is the main α₁ globulin?

α₁-antitrypsin (AAT).

Function of α₁-antitrypsin?

protease inhibitor

what happens with AAT deficiency?

emphysema (lung damage causing shortness of breath) and liver cirrhosis

is AAT an acute phase reactant?

yes, positive acute phase reactant

what is the function of haptoglobin

binds free hemoglobin released from RBCs

what does low haptoglobin indicate?

increased hemolysis

is haptoglobin acute phase reactant?

yes, positive acute phase reactant

what is the function of ceruloplasmin?

transports copper

what disease is associated with low ceruloplasmin?

wilson’s disease (copper accumulation in organs)

is ceruloplasmin an acute phase reactant

yes positive acute phase reactant

what is the function of of transferrin?

transports iron

what happens to transferrin in iron deficiency anemia?

increased levels (low saturation, but more protein trying to bind iron)

is transferrin an acute phase reactant?

negative acute phase reactant (decreases in inflammation)

what happens when transferrin is low?

less iron transport —> decreased hemoglobin —> anemia

what are beta compliment proteins (C3 and C4)?

part of innate immunity, tag and destroy pathogens

what are gamma globulins?

immunoglobulins (antibodies) produced by plasma cells

what type of immunity are gamma globulins?

adaptive immunity (recognize and neutralize pathogens)

what is hypogammaglobulinemia?

low antibodies —> immunodeficiency

what is hypergammaglobulinemia?

high antibodies, can be polyclonal (chronic inflammation, liver disease) or monoclonal (plasma cell neoplasm ex. multiple myeloma)

Globulins – key points?

• α₁: AAT (protease inhibitor; deficiency → emphysema, cirrhosis; +APR)

• α₂: Haptoglobin (binds free Hb, ↓ in hemolysis; +APR), Ceruloplasmin (copper transport; ↓ in Wilson’s; +APR)

• β: Transferrin (iron transport; ↑ in IDA; –APR), Complement C3/C4 (innate immunity)

• γ: Immunoglobulins (adaptive immunity; ↓ = immunodeficiency, ↑ = polyclonal inflammation/liver disease or monoclonal neoplasm).

what does troponin C do?

binds calcium

what does troponin I do?

inhibits actin-myosin interaction

what does troponin T do?

binds tropomyosin

what is the gold-standard biomarker for myocardial infarction (MI)?

cardiac troponins

troponin timeline in MI?

detectable 3-6 hours, peaks 12-24 hours, remains elevated up to 14 days

what triggers secretion of natriuretic peptides?

myocardial stretch and volume overload

what are the types of natriuretic peptides and their sources?

• ANP – atria

• BNP – ventricles

• CNP – endothelium

• DNP – snake venom

which natriuretic peptide is clinically used for heart failure?

BNP and NT-proBNP

what do BNP/NT-proBNP levels indicate?

elevated: ventricular dysfunction

low levels rule out heart failure

what is fibronectin

high molecular weight glycoprotein in plasma and extracellular matrix (‘biological glue)

functions of fibronectin?

cell adhesion, wound healing, tissue repair, embryonic development, blood clotting

what is fetal fibronectin testing used for?

vaginal swab to predict risk of preterm labor (high negative predictive value)

when are fibronectin levels decreased?

disseminated intravascular coagulation (DIC), due to consumption

where is fibronectin synthesized?

liver and connective tissue

what is cystatin C

small cysteine protease inhibitor, produced constantly by all nucleated cells

how is cystatin C handled in the kidney?

filtered by glomerulus → reabsorbed and catabolized in proximal tubules

what does cystatin C measure clinically?

marker of glomerular filtration rate (GFR)

why is cystatin C more reliable than creatinine?

independent of muscle mass, better for elderly, children, or malnourished patients

how is cystatin C measured?

immunoassays

what does high Cystatin C indicate?

reduced kidney function (low GFR)

troponin key points:

MI marker; C binds Ca²⁺, I inhibits actin-myosin, T binds tropomyosin; ↑ 3–6 hrs, peak 12–24 hrs, persists 14 d.

natriutetic peptides - key points

ANP (atria), BNP (ventricles), CNP (endothelium), DNP (snake venom); BNP/NT-proBNP → HF diagnosis (↑ = dysfunction, ↓ rules out).

fibronectin - key points

ECM glycoprotein for adhesion, repair, clotting; fetal fibronectin predicts preterm labor; ↓ in DIC.

cystatin C - key points

Constantly made by all nucleated cells; tracks GFR; more reliable than creatinine; ↑ = kidney dysfunction.

what is hypoproteinemia

low total serum protein (esp. albumin)

what clinical feature is associated with hypoproteinemia?

edema (low albumin → ↓ oncotic pressure → fluid leaks into tissues)

what happens to urine protein in nephrotic syndrome?

proteinuria (albuminuria)

what kidney condition causes protein loss?

nephrotic syndrome → albuminuria

what GI condition causes protein loss?

protein-losing enteropathy

what condition causes increased protein breakdown?

trauma, sepsis, burns, malignancy

what causes decreased protein intake/absorption

malnutrition and malabsorption (celiacs, Crohns)

what is hyperproteinemia?

elevated serum protein

which protein fraction usually increases in hyperproteinemia?

globulins (increase total proteins, increase globulins)

what lab method distinguished monoclonal from polyclonal increases?

Serum protein electrophoresis (SPE)

what does an M spike on SPE indicate?

monoclonal gammopathy (ex. multiple myeloma)

what cuases relative hyperproteinemia?

dehydration (vomiting, diarrhea, sweating)

what causes polyclonal gammopathy?

chronic infection and autoimmune disease

what causes monoclonal gammopathy

plasma cell neoplasms (ex. multiple myeloma)

what is hyperviscosity syndrome?

complication of hyperproteinemia causing blurred vision, headache, and thrombosis

what conditions can lead to hyperviscosity syndrome?

severe hyperproteinemia (ex. multiple myeloma, dehydration)

what is the structure of hemoglobin?

quaternary protein, tetramer (2 alpha and 2 beta chains) each with a heme group containing iron.

how many o2 molecules can each hemoglobin carry?

up to 4

what is the main function of hemoglobin?

transports o2 from lungs to tissues and co2/h+ back to lungs, also buffers blood pH.

where is hemoglobin synthesized

in immature RBCs in bone marrow

what is the overall role of hemoglobin

o2 transport with cooperative binding (teamwork)

what is the structure of myoglobin?

small heme-containing monomeric protein in skeletal and cardiac muscle.

what is the function of myoglobin?

acts as an o2 reservoir in muscle and facilitates o2 diffution within cells