describe general chemical structure of an alpha amino acid
includes amino group, carboxyl group, hydrogen and R group
diagnosic approach to protein abnormalities
1. patient presents
2. total serum
3. albumin level (albumin/globulin levels)
4. if a/g abnormal then do serum protein electrophoresis
5. if Serum pe is normal then do urine PE
if Urine PE is normal there is no problem
2. total serum
3. albumin level (albumin/globulin levels)
4. if a/g abnormal then do serum protein electrophoresis
5. if Serum pe is normal then do urine PE
if Urine PE is normal there is no problem
albumin/globulin ratio
norms, and diseases associated
norms, and diseases associated
Norm is greater than one. anything less than one is indicator of disease.
If liver malfunctions Alb goes down, but total unaffected.
Hyperproteinemia-lots of protein in blood stream
causes: dehydration (proportionate decrease in all fractions
or multiple myeloma-increases in one clone of Ig but alb does not change->low alb/glu
Hypoproteinemia-
decrease protein in blood
alb/glb ratio decreased
decreased intake-malnutrition or malabsorption-=-> no change or decrease in ratio
If liver malfunctions Alb goes down, but total unaffected.
Hyperproteinemia-lots of protein in blood stream
causes: dehydration (proportionate decrease in all fractions
or multiple myeloma-increases in one clone of Ig but alb does not change->low alb/glu
Hypoproteinemia-
decrease protein in blood
alb/glb ratio decreased
decreased intake-malnutrition or malabsorption-=-> no change or decrease in ratio
albumin/globulin ratio
norms, and diseases associated
norms, and diseases associated
Norm is greater than one. anything less than one is indicator of disease.
If liver malfunctions Alb goes down, but total unaffected.
Hyperproteinemia-lots of protein in blood stream
causes: dehydration (proportionate decrease in all fractions
or multiple myeloma-increases in one clone of Ig but alb does not change->low alb/glu
Hypoproteinemia-
decrease protein in blood
alb/glb ratio decreased
decreased intake-malnutrition or malabsorption-=-> no change or decrease in ratio
If liver malfunctions Alb goes down, but total unaffected.
Hyperproteinemia-lots of protein in blood stream
causes: dehydration (proportionate decrease in all fractions
or multiple myeloma-increases in one clone of Ig but alb does not change->low alb/glu
Hypoproteinemia-
decrease protein in blood
alb/glb ratio decreased
decreased intake-malnutrition or malabsorption-=-> no change or decrease in ratio
Method of Guthrie test
uses bacillus subtilis and beta 2 thienylalamine on a medium.
betal 2 theinylalmine
betal 2 theinylalmine
What is positive for PKU in guthrie test and why?
The bacteria grows on the plate.
because the extra phenylalanine created in infants with PKU inhibits the b-2 thienylanamine which inhibits growth (double negative=postive growth)
because the extra phenylalanine created in infants with PKU inhibits the b-2 thienylanamine which inhibits growth (double negative=postive growth)
tyrosinemia
inhibits fumurate synthesis pathway
fumarylacetoacetate hydrolase defficiency which produces the byproducts succinyl acetoacetate, and succinyl acetone
symptoms includ cabbage like odor ricketts, failure to thrive
fumarylacetoacetate hydrolase defficiency which produces the byproducts succinyl acetoacetate, and succinyl acetone
symptoms includ cabbage like odor ricketts, failure to thrive
alkaptonuria
inhibits fumarate synthesis pathway
caused by homogentisate oxidase deficieny
causes buildup of homogentisic acid
symptoms include benign igment deposit->arthritis
andnd brown/black urine
changes in diet for treatment (low in tyrosine/phenylalanine)
caused by homogentisate oxidase deficieny
causes buildup of homogentisic acid
symptoms include benign igment deposit->arthritis
andnd brown/black urine
changes in diet for treatment (low in tyrosine/phenylalanine)
Maple Syrup Urine disease
block in anabolisis of branched chain amino acids
can't changed branced alpha keto acids to CoA deriviatives because of lack in alpha ketoacid dehydrogenase deficiency
branched chain ketoacids create maple syrup (ketones smell sweet)
symptoms-difficult to feed, vomiting, lethargy, ketosis, urin smells like maple syrup, neuro damage,
treatment-diet of mixed pure amino acids
can't changed branced alpha keto acids to CoA deriviatives because of lack in alpha ketoacid dehydrogenase deficiency
branched chain ketoacids create maple syrup (ketones smell sweet)
symptoms-difficult to feed, vomiting, lethargy, ketosis, urin smells like maple syrup, neuro damage,
treatment-diet of mixed pure amino acids
Homocystinuria
block in methionine to cystein chain
type I homocystinuria can't change homocystein to cystathionine because of lack of cystathione synthase.
homocysteine builds up and is excreted in urine
symptoms-thrombosis, osteoporosis, dislocated lens, mental retardation, scoliosis, concave in chest
treatment-diet- restricted methionine, increased cystein, high vitamin B6
type I homocystinuria can't change homocystein to cystathionine because of lack of cystathione synthase.
homocysteine builds up and is excreted in urine
symptoms-thrombosis, osteoporosis, dislocated lens, mental retardation, scoliosis, concave in chest
treatment-diet- restricted methionine, increased cystein, high vitamin B6
describe a peptide bond
The carboxyl of one aa and the amino group of another condense (lose h20) an dform peptide bond. so chain is NCC NCC. peptide bond is shorter and stronger than the CN bond.
the CCNC bonds are in a plane
the CCNC bonds are in a plane
levels of protein structure
primary-chain of amino acids, not functional, but eventually determines structure
secondary- alpha helix or beta pleated sheets, formed by h bonding with itself (alpha) or between chains (beta)
Tertiary- folding of a chain and secondary structure to form subunits, uses disulfide bonds, hphobic/hphilic interactions
quarternary-very functional form of protein-spacial arrangement of subunits via diverse bonding mechanisms
secondary- alpha helix or beta pleated sheets, formed by h bonding with itself (alpha) or between chains (beta)
Tertiary- folding of a chain and secondary structure to form subunits, uses disulfide bonds, hphobic/hphilic interactions
quarternary-very functional form of protein-spacial arrangement of subunits via diverse bonding mechanisms
Kjeldahl reaction
reference method that finds nitrogen in a sample to find amount of protein
sometimes a problem bc n is sometimes in r group
protein and sulfuric acid heated and added to acid until ammonia forms. measure ammonia to find nitrogen content
sometimes a problem bc n is sometimes in r group
protein and sulfuric acid heated and added to acid until ammonia forms. measure ammonia to find nitrogen content
Normal behavior in serum protein electrophoresis
in 8.6 solution, acids are negative and go to positive pole(cathode).
The largest/closest to (+) is albumin, followed by alpha 1, alpha2 bumps of about a quarter of the size followed by beta, a little smaller and a wide spread gamma charge.
The largest/closest to (+) is albumin, followed by alpha 1, alpha2 bumps of about a quarter of the size followed by beta, a little smaller and a wide spread gamma charge.
rank 5 protein fractions by speed of migration
albumin, alpha 1, alpha 2, beta, gamma
albumin and electrophoresis
maintains colloidal osmotic pressure and is a transport protein
is a negative acute phase protein meaning if bump is smaller there's probably some sort of inflammation. when it is decrease there is less osmotic pressure and edema increases
is a negative acute phase protein meaning if bump is smaller there's probably some sort of inflammation. when it is decrease there is less osmotic pressure and edema increases
alpha 1 globulin and electrophoresis
includes alpha1 antitrypsin which inhibits trypsin, if low it indicates emphysema, but if high it indicates inflammation (acute phase protein
alpha 1 acid glycoprotein increases in cronic inflamation and increases a lot in malignant disease (acute phase protein
alpha 1 fetoprotein-fetal protein at embryonic stage, increases in maternal serum and amniotic fluid lead to fetal open neural tube defect, extreme rises in adults indicates hepatocellular or germ cell carcinoma. if decreased in embryo, may cause down's syndrome
alpha 1 acid glycoprotein increases in cronic inflamation and increases a lot in malignant disease (acute phase protein
alpha 1 fetoprotein-fetal protein at embryonic stage, increases in maternal serum and amniotic fluid lead to fetal open neural tube defect, extreme rises in adults indicates hepatocellular or germ cell carcinoma. if decreased in embryo, may cause down's syndrome
alpha 2 globulin types and behavior in electrophoresis
increases
alpha macroglobulin- inhibits trypsin which lead to dephrotic syndrome which leads to loss of protein. also increases in cirrhosis and diabete millitus
haptoglobin- binds to free hemoglobin and is lowered in hemolytic anemia, but increased in inflammation (acute phase protein)
ceruloplasmin binds copper and is lwoered in disease and increase in inflammation (acute phase protein)
alpha macroglobulin- inhibits trypsin which lead to dephrotic syndrome which leads to loss of protein. also increases in cirrhosis and diabete millitus
haptoglobin- binds to free hemoglobin and is lowered in hemolytic anemia, but increased in inflammation (acute phase protein)
ceruloplasmin binds copper and is lwoered in disease and increase in inflammation (acute phase protein)
beta globulin types and electrophoresis behavior
transferrin-binds and transports iron, raised in iron defiiciney anemia, lowers in acute phase reaction
complement- acute phase protein, lowers in auto immune disease
complement- acute phase protein, lowers in auto immune disease
gamma globulin types and electrophoresis behavior
immuno globulins
C reactive protein-increase in inflammation
C reactive protein-increase in inflammation
acute phase reactants and biggest/most responsive
alpha 1 antitrypsin -2
alpha 1 acid glycoprotein
haptoglobin
ceruloplasmin
complement-3 (C3 especially)
fibrinogen
CRP-biggest and most responsive
alpha 1 acid glycoprotein
haptoglobin
ceruloplasmin
complement-3 (C3 especially)
fibrinogen
CRP-biggest and most responsive
paraproteins
protein like substances like Ig's or Ig light chains. presence indicates multiple myeloma
M-band or Spike
one very large spike in EP that is not albumin that indicates monoclonal expansion
monoclonal gammopathies
multiple myelomas- (decreased normal plasma cells) decreased antibodiesholes in bones lead to calcium release) and . elevated monoclonal Ig's in serum/urine. must have 1 major and 1 minor indicator or 3 minor indicators
waldenstrom's macroglobulinemia (IgM class malignancy) causes fatigue mucous membrane bleeding and enlarged lymph nodes and spleen-increased protein/viscosity, normochromic/normocytic anemia, rouleaux blood smear, hypercellular bone marrow, lots of IgM (plasmaphoresis and chemo)
clone of differentiated B cells creates Ig with either light chain only or heavy chain only
waldenstrom's macroglobulinemia (IgM class malignancy) causes fatigue mucous membrane bleeding and enlarged lymph nodes and spleen-increased protein/viscosity, normochromic/normocytic anemia, rouleaux blood smear, hypercellular bone marrow, lots of IgM (plasmaphoresis and chemo)
clone of differentiated B cells creates Ig with either light chain only or heavy chain only
characteristics of EP with nephrotic syndrom
all proteins lowered but alpha 2 (high haptoglobin and high alpha 2 amcroglobulin)
Acute phase rxn EP
little lower albumin
increase in alpha1 and alpha 2
beta may change (transferrin lowers but c3/c4 raise)
gamma increase (increased crp)
increase in alpha1 and alpha 2
beta may change (transferrin lowers but c3/c4 raise)
gamma increase (increased crp)
liver cirrhosis EP
creases beta gamma bridge and lowers albumin because it's made in liver. (IgA, M and G increased)
normal composition of urine proteins
lots of albumin (glomerular filtration) with a little uromucoid (tubular secretion) and minor other proteins
50-80 gm/day (at rest)
50-80 gm/day (at rest)
CSF protein composition and contents
15-45 mg/dL
low moleular weight plasma proteins
retinal binding protein, albumin transferrin, IgG and other come from outside of the cavity
transferrin, IgG are synthesized intrathecally.
low moleular weight plasma proteins
retinal binding protein, albumin transferrin, IgG and other come from outside of the cavity
transferrin, IgG are synthesized intrathecally.
Case: 65 y/o with sever back and leg pain. has unexplained wight loss, frequent bloody noses and reoccuring infection.
Lab: normal WBC, lower RBC, Heme-decreased, platelets low, calcium high, Alb/Glob less than one, albumin a little low
Lab: normal WBC, lower RBC, Heme-decreased, platelets low, calcium high, Alb/Glob less than one, albumin a little low
possible multiple myeloma
Calcium produced by holes in bones, Red blood cells are decreased
has decreased plasma cells so reoccuring infection is caused by no Ab's, platelets are low because of thromboocytothemia
Calcium produced by holes in bones, Red blood cells are decreased
has decreased plasma cells so reoccuring infection is caused by no Ab's, platelets are low because of thromboocytothemia
polyclonal gammopathy
many kinds of clones being produced Antigen causes multiple types of Ab's to be created. Ab's target one epitope so many Ab's react to same Ag
caused by infection autoimmune disease or neoplasm
caused by infection autoimmune disease or neoplasm
Biuret reaction
method for finding amount of protein in sample
add copper and biuret. copper crosslinks C=O groups.
must have a tripeptide to be detected because in order to crosslink the c=o's there has to be that many.
test shows c=o's not just amino acids
add copper and biuret. copper crosslinks C=O groups.
must have a tripeptide to be detected because in order to crosslink the c=o's there has to be that many.
test shows c=o's not just amino acids
refractive index
principe: light changes direction when passing from one medium to another. more protein more refraction sin theta incidence/sin theta r
sources of error-altered proteins, hemolysis, temperature (as temp increases RI decreases, standard and sample should be same temp,
Sensitivity: high concentrations (grams/dL)
sources of error-altered proteins, hemolysis, temperature (as temp increases RI decreases, standard and sample should be same temp,
Sensitivity: high concentrations (grams/dL)
turbidimetry
principle: reduction of light transmitted (light blocked)
protein must be exposed to weak acid to create particulate proteins suspended
sources error: # and cross sectional area of particles, timing (longer you let sit, the more transmittance), temp- high temp makes particulates faster and more likely to deflect light, problems with alb/ glob ratio
sensitivity low concentrations (mg/dL) good for urine and spinal fluid
protein must be exposed to weak acid to create particulate proteins suspended
sources error: # and cross sectional area of particles, timing (longer you let sit, the more transmittance), temp- high temp makes particulates faster and more likely to deflect light, problems with alb/ glob ratio
sensitivity low concentrations (mg/dL) good for urine and spinal fluid
2 major functions of gamma glutamyl cycle
1. transport of amino acids across cell membrantes to be assembled
2. synthesis of glutathione (which is glutamyl reduced by NADPH)
2. synthesis of glutathione (which is glutamyl reduced by NADPH)
functions of gluatathione
antioxidant, iron in ferrous state, cell membrane structure
what happens in glutathione deficiencies?
hemolytic anemias because of lack of cell membrane support.
aminoacidopathies definition
inborn errors of amino acid metabolism
includes: PKU, thyrosinemia, alkaptonuria, maple syrup urine diseases and homocystinuria
includes: PKU, thyrosinemia, alkaptonuria, maple syrup urine diseases and homocystinuria
PKU types
-Type 1-Phenylalanine hydroxylase deficiency
-Type 4 and 5- dihydropteridine reductase deficiency
-Type 4 and 5- dihydropteridine reductase deficiency
symptoms of PKU
mental retardation, impaired psychomotor development, light/fair skina and blue eyes (bc phenylalanine makes melanin, no melanin, no tint), musty odor (increased phenylacetate) seizures, hyperactivity
Testing for PKU
Guthrie Test, Tandem Mass Spec and others (ELISA, chromatograph, fluorometric)
Testing for PKU
Guthrie Test, Tandem Mass Spec and others (ELISA, chromatograph, fluorometric)
Testing for PKU
Guthrie Test, Tandem Mass Spec and others (ELISA, chromatograph, fluorometric)
Testing for PKU
Guthrie Test, Tandem Mass Spec and others (ELISA, chromatograph, fluorometric)
Define Zwitterion
aka ampholyte
a molecule that can be turned into a negative or poisitive ion (amino acids are zwitterions)
a molecule that can be turned into a negative or poisitive ion (amino acids are zwitterions)
how do amino acids behave in acids/bases
in acids a.a. becomes positive and in bases amino acid becomes negative
hydrophobic Amino acids
glyceine, alanine, proline, valine, methionine, isoleucine, leucine, tryptophan
hydrophilic amino acids
tryptophan, phenyalanine, cysteine, threonine, serine, gutamine, asparagine
behavior of charged a.a.'s in water
go to surface of molecule-->wants to be closest to water
Roles of Amino Acids
1. Biosynthesis-proteins and other (heme, nucleotides, amino acids, hormones)
2. Energy-Keto and Glucogenic
2. Energy-Keto and Glucogenic
Ketogenic vs. glucogenic
Keto -enters at acetyl Co A with Acetoacetyl CoA (fat pathway)
Glucogenic-enters as pyruvate
both types of energy contribute to kreb's cycle and create NH2 as a waste product which is disposed of in urea
Glucogenic-enters as pyruvate
both types of energy contribute to kreb's cycle and create NH2 as a waste product which is disposed of in urea
digestive enzyme and pathway of it in stomach
pepsinogen + acid > pepsin
pepsin + protein> peptides and a few free amino acids
pepsin + protein> peptides and a few free amino acids
pancreatic digestive enzyme and pathway
trypsinogen (inactive) + enterokinase (from intestines)> trypsin (active)
Trypsin + Pancreatic zymogens (inactive)>proteases
Trypsin + Pancreatic zymogens (inactive)>proteases
Kartensatzinfo:
Autor: skunz11
Oberthema: Bio Chemisty
Thema: Clinical Bio Chem
Veröffentlicht: 02.03.2010
Tags: Proteins
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