B7/8 plasma proteome + albumin Flashcards
what is the role of the blood (9)
-oxygen transport
-nutrient transport
-hormone transport
-waste removal
-thermoregulation
-clotting
-pH balance
-osmotic balance
-immune function
what are the components of blood when separated
!! centrifugation with fibrinogen as a clotting factor:
- Plasma (55%)
- cellular component (44%)
- buffy coat (1%) - leukocytes
what are the general components of blood plasma
91% water
7% proteins: albumins, globulins, fibrinogen, prothrombin
2% other solutions like ions, nutrients, waste products and gases
Describe the electrolyte composition of plasma, interstitial fluid and intracellular fluid (ions)
SOS: blood plasma and interstitial fluid have similar compositions, but intracellular fluid is the opposite
Plasma: Na+/Cl-
ICF: K+ / HPO4-
HCO3- is the exeption bcos its conc is almost the same in ICF/plasma
what are the ways in which the body inputs and outputs fluids
INPUT: food, drinks, oxidation (H20 product)
OUTPUT: urine, skin/lungs and faeces
!! under physiological conditions these are equal in magnitude
what factors does the fluid volume and distribution of a person depend on?
! ratio of skeletal muscle to adipose tissue
-overal weight
-age / sex
-diet and water intaken
-genetics
pH level in the blood + reasoning
VERY NARROW RANGE: 7.35-7.45
4 CHEMICAL BUFFERS:
-carbonic acid/bicarbonate
-plasma proteins
-Hb
-phosphates
what is the normal range of glycemia
70-100 mg/dl
(there is a sharp increase after meals which induces insulin release, and an intolerance to this leads to diabetes)
why is it imporant that cholesterol doesnt build up in the blood
- there is no biochemical way to catabolise cholesterol (only when it is incorporated into substances like steroids)
- a buildup of cholesterol leads to plaque formation and atherosclerosis
what are the main lipids of plasma and what are their origins
-cholesterol (free or ester)
-TAGs
-fatty acids bound on albumin protein
-phospholipids and sphingolipids
-bile acids
ORIGINS: dietary, breakdown of adipose tissue, endogenous biosynthesis in the presence of glucose
describe the role of the lipoproteins present in blood plasma
- chylomicrons: transport EXOGENOUS TAGs and cholesterol to peripheral tissues and liver from the small intestine where they are digested
- VLDL: made by liver and released to the bloodstream to carry ENDOGENOUS TAGs to tissues
- LDL: transport cholesterol from the liver into the bloodstream
- HDL: remove cholesterol from the blood stream and into the liver
what are the amino acids present in plasma and what is their origin
-alanine (product of skeletal muscles)
-glutamine (main NH3 carrier)
!! very low values of acidic aa (so that the pH isnt thrown off)
SOURCES: diet, breakdown of proteins (catabolism), biosynthesis (from carbs, amino acids & lipids)
what are the functions of the plasma proteins (5)
-create colloid osmotic pressure
-binding and transport of substances
-buffer properties
-Coagulation cascade
-hormone precursors
describe the general features of plasma proteins
-liver synthesised (usually on membrane bound polyribosomes)
-usually undergo post translational modifications and most are glycoproteins
-each has a diff characteristic half life and circulation time
half life of Hb and albumin
Hb: 120 days
Albumin: 15-19 days
what are the diff classes of the globulin protein family + where are they synthesised
alpha1, alpha2, beta -> synthesised in liver
gamma-> synthesised in reticuloendothelial system
proteins of the alpha1 globulin fraction (3)
- orosomucoid: carb rich, transports hexosamine to tissues used for glycosylation
- a1-glycoprotein
- a-lipoprotein: transport carrier of lipids in blood
proteins of the alpha 2 globulin fraction (5)
- a2-glycoproteins
2/3. prothrombin & plasminogen: inactive precursors of plasmin and thrombin for clotting
- haptoglobulin: glycoproteins that bind with any Hb found in the plasma after RBC lysis (hence prevents the excretion of Hb and Fe)
- ceruloplasmin: glycoprotein for copper metabolism (95% of Cu of body bound to this protein)
proteins of the beta globulin fraction (1)
VERY LIPID RICH beta lipoproteins:
1. transferrin: transport non heme Fe
describe gamma globulins
IMMUNOGLOBULINS:
-antibody activity
-IgG/A/M classification based on their elecrophoretic mobility
what technique is used to measure amount of globulins
CELLULOSE ZONE ELECTROPHORESIS: uses a small amount of serum applied to acetate cellulose strip to separate and visualise the protein bands and create SERUM PROTEIN PROFILES (which can be interpreted as either physiological or abnormal)
diagnostic relevance of plasma proteins
-transport proteins (albumin /ceruloplasmin/ haptoglobin / transferrin)
-proteins that show immune response (gamma globulins and clotting proteins)
-enzymes
describe the structure of albumin
- strongly negatively charged
- 3 DOMAINS each one having a subdomain A and B containing 4 and 6 helixes respectively
SOS: Large amount of acidic aa (glutamine / aspartate) and basic aa (lysine / arginine) which makes it HIGHLY SOLUBLE IN AQUEOUS ENVIRONMENTS
-presence of disulfide bonds
!!! coded for by the ALB gene and has more than 80 genetic variations
what is the distribution of albumin?
40% in plasma and 60% in extracellular space
-also present in CSF and amniotic fluid
!! if found in urine it shows pathological proteinuria
desribe the process of albumin turnover
RATIO between synthesis and degradation
SYNTHESIS: preproalbumin - proalbumin - albumin
DEGRADATION:
-catabolised by various tissues (muscles, kidneys, liver, GI system) by being taking up via endocytosis and then proteolysis –> aa then recycle into body pool
what factors control the albumin turnover (3)
-colloid osmotic pressure
-protein intake
-inflammatory cytokines (decrease albumin synthesis)
describe how albumin is taken into cells
ENDOCYTOSIS: interacts with several receptors:
- FcRn-albumin complex: protects albumin from lysosomal degradation
- Megalin-cubilin complex: binds to albumin and internalises it via endocytosis and degradation into lysosomes
describe the role of albumin as a multifunctional protein (5)
- establishes 80% of oncotic pressure (large and doesnt pass through endothelium - hence low albumin causes edema)
- acid base balance (95% of non bicarbonate buffering capacity bcos it has acidic and basic aas)
- SUBSTANCE binding and transport (Ca / PUFAs / ROS / Cu2+ / bilirubin) bcos of diff binding sites
- DRUG binding and transport (warfarin, salicylates) - can also bind heme which inhibits drug binding
- antioxidant (Cys34 binding site binds and neutralises ROS bcos it contains SOD/ glutathione) - doesnt exist under certain genetic variations
What are AGE?
ADVANCED GLYCATED END PRODUCTS: accumulate in tissues of individuals with prolonged hyperglycemia (eg poorly controlled diabetes)
EG - > glycated Hb or albumin (the longer the half life of the protein the longer the glycated version will stay in the blood and hence they can act as markers for hyperglycemic diseases)
How are AGEs formed?
MAILLARD REACTION: spontaneous chemical reaction (non enzymatic) where reducing sugar groups are added to aa groups of proteins (usually lysine or arginine) due to prolonged conditions of hyperglycemia
RESULT: forms a schiff base and an AMADORI PRODUCT (stable and irreversible ketamine)
what does albumin glycation result in?
-loss of function, decrease in binding ability due to structural modification, loss of antioxidant functions –> can cause inflammation and membrane damage
!! can also act as a marker for hyperglycemic disease
what might cause changes in albumin content + what does an abnormal albumin content indicate clinically?
SLIGHT DECREASE: injured hepatocytes, cirrhosis, malnutrition and inflammatory conditions
EXTENSIVE DECREASE: proteinuria, loss from burns, protein-losing intestinal diseases
HIGH: dehydration from diarehea or acute infection
!! a low albumin can cause edemas
