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Proteins
Proteins
126
Chemistry
01/18/2012

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Term
nucleoside
Definition
contain purine/pyrimidine base covalently bonded to a sugar
Term
nucleotide
Definition
monomer of nucleic acids, nucleoside to which 1-3 Phosphate groups are covalently bonded
Term
nucleic acids
Definition
polymer of nucleotides covalently linked by phosphodiester bonds. 2 Types: deoxyribonucleic and ribonucleic acids
Term
deoxyribonucleic acid (DNA)
Definition
double-stranded nucleic acid molecule composed of repeating nucleotides
Term
ribonucleic acid (RNA)
Definition
single-stranded nucleic acid molecule found in every living cell
Term
gene
Definition
single-stranded section of DNA, codes for proteins
Term
chromosomes
Definition
linear double-stranded DNA molecules that carry all of an organisms genetic info. During cell division a new copy of chrom. is produced for new cell, thereby conserving genetic info.
Term
metabolism
Definition
sum of all biochem. reactions that occur w/in cell. Includes building up and breaking down of 4 key bio. molecules
Term
nitrogenous base
Definition
heterocyclic amines, consists of carbon and nitrogen
Term
purines
Definition
contain 2 ring structures fused together
Term
pyrimidines
Definition
contain 1 ring structure
Term
Chemical components of nucleotides
Definition
a) pentose sugar
b) 1 to 3 phosphate groups (-PO4 ^3-)
c) nitrogenous base
d) double-stranded DNA, purine complementary paired to pyrimidine
Term
DNA components
Definition
1) nitrogenous bases
a)adenine b)guanine c)thymine d)cytosine

2)pentose sugar
3)phophate groups [-PO4 ^3-]
Term
DNA structure
Definition
1) double helix
2)nitrogen pairing always complementary, A-T and C-G, held together by weak hydrogen bonds. Called complementary base pairing.
3) 6x10^9 nucleotides in human DNA, called genome. Within genome are genes, code for proteins. Contains about 30,000 genes.
4)2 pairs of 23 chromosomes, 46 total. 23 from mom, 23 from dad.
5)mutation, change in DNA sequence. Can result in nucleotide substitutions, insertions, or deletions. Can have no effect, loss of protein function, or creation of new function.
Term
ribonucleic acid (RNA) components
Definition
1)nitrogenous base
a)adenine b)guanine c) uracil (replaces thymine) d)cytosine

2)pentose sugar
3)phosphate groups
Term
RNA structure
Definition
1)single stranded
2)complementary base pairing, A-U and G-C
Term
messenger RNA (mRNA)
Definition
carries genetic info. for protein from DNA to ribosomes
Term
ribosomal RNA (rRNA)
Definition
major structural and functional component of ribosomes. Are "platforms" on which protein synthesis occurs
Term
transfer RNA (tRNA)
Definition
in protein synthesis, role is to deliver correct amino acid to ribosome for incorporation into new protein molecule
Term
Transcription DNA-->RNA
Definition
a) gene (single strand of DNA) serves as a template for synthesis of RNA molecule. RNA produced will complement DNA coding.
b) occurs in cell nucleus and is catalyzed by enzyme RNA polymerase. Final RNA product is exported from nucleus to cell cytoplasm.
Term
Translation mRNA-->protein
Definition
a) mRNA is used as template to synthesize protein
b) occurs in cell cytoplasm on ribosomes.
c)converts sequence of nucleotides in mRNA into sequence of amino acids synthesize new polypeptide. Every 3 mRNA nucleotides encode single amino acid, this sequence is called codon.
d) tRNA decodes info. in mRNA into amino acid sequence by recognizing codon thru complementary base pairing
e) each tRNA binds 1 specific amino acid, recognizes one codon thru complementary base pairing. Results in correct amino acid being delivered to ribosomal complex and being incorporated in correct order into new protein
Term
replication
Definition
a) DNA is copied. Bases for biological inheritance in all living organisms as cells must replicate DNA before dividing
b) occurs in nucleus
c)DNA strands separated, permits enzyme DNA polymerase to produce 2 complementary base paired DNA strands.
d)each DNA molecule will include 1 of the original strands and 1 new complementary strand. Process is semiconservative in nature.
Term
protein
Definition
polymer of amino acids covalently joined by peptide bonds. Chemical elements in all proteins: Carbon, hydrogen, oxygen, and nitrogen. 20 common amino acids, rep. by single letter or 3 letter abbrev., have variable radical-R group. Over 50,000 estimated human proteins.
Term
R group
Definition
either hydrophobic/hydrophilic, can be acidic/basic. Chemical properties result in protein's function.
Term
amino acids
Definition
monomeric subunit of proteins, composed of central carbon atom bonded to amino group (-NH2), carboxyl group (-COOH), hydrogen atom, and variable radical group of atoms denoted by letter R.
Term
peptide bond
Definition
covalent bond formed btwn carboxyl group of 1 amino acid and amino group of another. Polymers, of more than 2 amino acids are called polypeptides instead of proteins.
Term
zwitterion
Definition
ion that has both pos. and neg. charge. At physiological pH, amino acids form these as amino group is protonated and carboxyl group is dissociated
Term
denaturation
Definition
process which organized structure of protein is disrupted. Results in loss of function that is often permanent.
Term
acute phase reactants
Definition
group of proteins whose plasma concentrations change following trauma, burns, infection, inflammations, and other related conditions.
Term
cryoglobulins
Definition
abnormal globulins occassionally encountered in serum can precipitate when serum is cooled to low temp. but redissolved when serum is rewarmed to body temp. (37 deg. Cel)
Term
immunoglobulins
Definition
group of plasma proteins that recognize and bind foreign antigens. aka antibodies.
Term
protein primary structure
Definition
linear sequence of amino acids (i.e. polypeptide) held together by peptide bonds
Term
protein secondary structure
Definition
folding of primary structure of protein, this folding is caused by noncovalent interactions, principally hydrogen bonds. Alpha helix and beta pleated sheet.
Term
protein tertiary structure
Definition
overall 3-dimensional folding of polypeptide resulting from additional folding beyond the secondary structure, caused by noncovalent interactions
Term
protein quanternary structure
Definition
overall 3-dimensional folding of 2 or more polypeptides together
Term
globular proteins
Definition
have relatively short primary structures (i.e. amino acid sequences), they constitute most of the proteins in body and circulating in your serum. Have compact, spherical, 3-dim. structure, and are generally soluble in salt solutions.
Term
examples of globular proteins
Definition
albumin, antibodies, nearly all enzymes, hormones, and hemoglobin.
Term
fibrous proteins
Definition
usually relatively long and are arranged in fibers/sheets that contain extensive amounts of one form of secondary structure. Insoluble in salt solutions, represent principal structural proteins of body.
Term
examples of fibrous proteins
Definition
collagen, elastin, keratin, actin, and myosin
Term
Protein functions
Definition
1) main component of immune system (antibodies)
2) catalyze biochem. reactions (enzymes)
3) transport molecules thruout body (hemoglobin)
4) regulatory roles (insulin hormone)
5) structure (keratin, collagen)
6) necessary for all forms of movement (actin, myosin)
7) nutrients (albumin and casein)
Term
hemoglobin (Hb)
Definition
oxygen-carrying protein found in red blood cells (erythrocytes), tetrameric protein containing 4 heme groups. Composed of 2 pairs of identical polypeptides. Lifespan is 120 days (RBC).
Term
functions of hemoglobin
Definition
gas transport and acid/base balance
Term
gas transport
Definition
involves transport of critical gas molecules. Hb reversibly transports O2 from lungs to tiss. of body. Hb can bind up to 4 O2 molecules. Oxygenated Hb/oxyhemglobin will travel to tiss. of body where needed, will release O2 molecules. Hb facilitates extraction of CO2 from tiss. back to lungs where it can be expelled. 5-10% of CO2 is associated with Hb.
Term
acid/base balance
Definition
assists in maintaining balance of blood. Hb is import. intracellular buffer. Hb readily accepts H+, forming deoxyhemoglobin (HHb), which is hemoglobin not bounded to O2 but capable of forming bond when O2 is available. Balance is maintained by binding/releasing H+ resulting from accumulation of acids as result of normal human metabolic processes.
Term
components of hemoglobin
Definition
4 subunits, each contain 1 heme and 1 globin
Term
heme
Definition
protoporphyrin IX ring, pyrrole rings are cyclic compounds that serve as building blocks for porphyrins, formed by linkage of 4 tetra pyrrole rings w/ 8 hydrogen ions. Single Fe ion will bond to center of ring to create heme group.
Term
Fe^+2 (ferrous) ion
Definition
allows O2 to reversibly bind and be transported thruout tissues of body. Ferric iron (Fe^+3) will complex to protoporphyrin ring but cannot bind O2, must be reduced. Blood contains majority of total iron present in body.
Term
globin
Definition
protein portion of molecule, composed of 2 pairs of polypeptide chains, contains 2 alpha and 2 beta globin polypeptides
Term
sites for heme synthesis
Definition
bone marrow, Hb production begins in rubricyte and continuous thru reticulocyte stage of RBC development. Stored iron is released from cell and delivered to maturing cell. Protoporphyrin IX ring combines with iron in mitochondria.
Term
heme synthesis
Definition
consists of an 8 step biochem. pathway which requires 8 diff. enzymes; 4 are located in mitochondria and 4 in cytosol.
Term
Aminolevelunic acid (ALA) synthase
Definition
enzyme that catalyzes in initial step in porphyrin synthesis. Rate limiting step in heme synthesis. Final product in pathway, heme, inhibits this enzyme and is example of feedback inhibition.
Term
Lead inhibition
Definition
inhibits all steps in porphyrin synthesis by denaturation of enzymes involved
Term
myoglobin
Definition
heme monomeric protein found in muscle tiss., contains one polypeptide and one protoporphyrin ring. Serves as reserve supply of O2. Greater affinity for O2 than Hb and requires lower O2 pressure to realse O2.
Term
Factors affecting oxygen transport
Definition
based on affinity for Hb to reversibly bind oxygen. Hemoglobin's affinity is dependent on partial pressure of oxygen (pO2), pH, temperature, and concentrations of 2,3-diphosphoglycerate (2,3 DPG)
Term
partial pressure of oxygen
Definition
P50 value is conventional index at which hemoglobin is 50% saturated with O2. Occurs at PO2 of 27mmHg. Decreased P50 is a shift to left, with increased affinity of hemoglobin, and impaired oxygen release to tiss. Increase of P50 is a shift to right, resulting in decreased oxygen affinity and increased release of oxygen, eases delivery of oxygen to tiss.
Term
P pH (Bohr Effect)
Definition
a) Increased blood acidity will decreaese pH causing a shift to right and lowering of Hb affinity for O2.
b) Decreased blood acidity will increase pH causing shift to left, increase of Hb affinity for O2.
Term
Christian Bohr
Definition
1904, discovered increase in blood CO2 levels would result in lowering pH of blood and require more O2 to be delivered to cells
Term
temperature
Definition
a) as body temp. increases, Hb more readily releases O2, causes shift to right of curve.
b) as body temp. decreases, Hb less readily releases O2, causes shift to left of curve.
Term
2,3-Diphosphoglycerate (2,3-DPG)
Definition
RBC's contain a lot. Most important factor in oxygen transport, phosphate which is present in human RBC at about same molar ratio as Hb. Binds to deoxyhemoglobin but not oxygenated form, diminished oxygen affinity of Hb, shifts dissociation curve to right. Essential in enabling Hb to unload O2 into tiss. that need it most. When pH drops, oxygen diss. curve moves to right, but resulting inhibition of binding to Hb corrects shift by an equal change to left.
Term
Types of Human Hemoglobin
Definition
Hb A, Hb A2, Hb A1c, Hb F.
Term
hemoglobin A
Definition
comprised of 2 alpha and 2 beta chains. Most common form of adult Hb. A2 is 2 alpha and 2 delta chains.
Term
hemoglobin A1c
Definition
non enzymatic modification Hb A that has been glycosylated. Often assayed via chromatography/electrophoresis. Concentrations serve as indicator for prolonged high glu. concentrations, increase can be seen in insulin-depen. diabetics. When previous 120 days glu. values was also elevated.
Term
hemoglobin F
Definition
major Hb of fetal life. Newborns (<1 month) reps. 70-90% of total Hb but then signif. declines and is replaced by adult Hb, after age 3 decreases less than 0.4% (adult range).
Term
billirubin
Definition
degradation product of heme portion of Hb. Protoporphyrin is converted into biliverdin then into bilirubin. It is the breakdown product of normal heme catabolism, yellow pigment that is released into blood stream where it binds with albumin. It is picked up by cells of liver and secreted with bile into intestines, further metabolized into urobilinogen, which is excreted in feces.
Term
factors that denature proteins
Definition
1) heat
2) organic solvents like alcohol
3) detergents
4) salting out
5) pH changes
6) heavy metals (mercury and lead)
7) mechanical stress
Term
heat
Definition
as temp. increases molecular motion increases. Weak hydrogen bonds will be disrupted by increased temps.
Term
organic solvent (i.e. alcohol)
Definition
polar solvents disrupt hydrogen bonds in proteins as well as form new hydrogen bonds
Term
detergents (soap)
Definition
have both a hydrophobic region and polar region. Can disrupt existing hydrogen bonds, also disrupting hydrophobic interactions import. to protein structure
Term
salting out
Definition
high concentrations of salts can dehydrate protein making it less soluble. Salts are used to change solubility of proteins and can be used to precipitate them.
Term
simple proteins
Definition
yield only amino acids upon hydrolysis
Term
examples of simple proteins
Definition
albumin, insulin, and fibrinogen
Term
conjugated proteins
Definition
upon hydrolysis yield amino acids and nonprotein substance.
Term
glycoproteins
Definition
contain covalently link carb. residues that make up small % by weight of molecule.
Term
phosphoproteins
Definition
have covalently linked phosphate groups
Term
lipoproteins
Definition
contain covalently linked lipid molecules, like cholesterol, triglyceride, and phospholipids.
Term
metalloproteins
Definition
contain ions and are often colored, like hemoglobin in RBC and chlorophyll in plants
Term
essential amino acids
Definition
must be provided in adult diet since human body cannot synthesize them.
Term
8 amino acids that are essential
Definition
isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
Term
nonessential amino acids
Definition
human body is able to synthesize, there are 12.
Term
liver
Definition
most import. site for protein production. Enzymes regulate concentration of essential amino acids.
Term
liver's use of amino acids
Definition
1)growth, maintenance, and repair
2)enzyme production
3)albumin
4)lipoproteins
Term
growth, maintenance, and repair
Definition
liver makes many secreted proteins used for within the body
Term
enzyme production
Definition
liver produces variety of enzymes that catalyze wide range of biochem. reactions.
Term
albumin
Definition
liver is the only source, the most abundant serum protein.
Term
lipoproteins
Definition
transport hydrophonic lipids such as HDL and LDL in blood.
Term
basic process of protein catabolism
Definition
1) begins with digestion of food
2) stomach, intestines, and pancreas all secrete proteolytic enzymes which eventually breakdown protein into free amino acids
3a) removal of amino group -NH2, converted by a series of biochem reactions into urea since NH3 is very very toxic, known as urea cycle.
3b) urea is waste product of degradation of amino acids into CO2 and NH3. Synthesized in liver and transported in blood to kidneys where it is turned into urine.
4) Breakdown of carbon backbone, converted into:
pyruvate, acetyl CoA, Krebs cycle intermediates (keto acids), free amino acids, and ultimately into fat or glu.
Term
methods of protein analysis
Definition
1) protein electrophoresis
2) biuret method
3) turbidimetry and nephelometry
4) albumin:globulin (A:G) ratio
5) kjeldahl procedure
Term
protein electrophoresis
Definition
separates proteins based upon their electrical charge. 5 distinct protein zones.
a) Albumin (normally largest fraction)
b) alpha 1-globulins
c) alpha 2-globulins
d) beta globulins
e) gamma globulins
Term
biuret method
Definition
most widely used procedure, measures total protein.
Term
turbidimetry and nephelometry
Definition
used to measure light scatter by Beer's Law. Can be used in automated systems. Precipitation of proteins is typically done by adding sulfosalicylic/tricholoracetic acid
Term
turbidimetry
Definition
measures decreased in amount of light as it passes thru particulate solution, used to measure small particles that reduce amount of light that passes thru sample and scatter light. Measured with simple spectrophotometer.
Term
nephelometry
Definition
used to measure amount of light as it scattered as it passes thru particulate solution, used to measure large parts. that deflect light forward. Intensity of light scatter is directly proportional to concentration of parts.
Term
albumin:globulin (A:G) ratio
Definition
Division of albumin by globulin levels. Provides sensitive indicator for disease detection, ranges from 1.5-2.5 in healthy individuals. Calc. by subtracting albumin levels from total protein level gives indirect estimate of globulin levels. Increases in gamma globulins directly proportional to presence and severity of disease. Albumins inversely proportional. Low ratios can be seen in liver disease, burns, malnutrition, diarrhea, myeloma, and lymphomas.
Term
kjeldahl procedure
Definition
measures total nitrogen, majority of nitrogen in body comes from protein catabolism. Used as reference against other methods for protein analysis.
Term
functions of albumin
Definition
1) primary contributor to COP, responsible fo 80% of COP.
2) source of free amino acids when catabolized
3) major transport protein of large organic anions in blood
Term
clinical signif. of albumin
Definition
hypoalbuminemia, low levels of albumin in blood
hyperalbuminemia, elevated levels
Term
clinical signif. of hypoalbuminemia
Definition
liver disease, acute phase response, nephrotic syndrome, and other protein loss syndromes
Term
clinical signif. of hyperalbuminemia
Definition
dehydration and artificial increase may result after prolonged tourniquet application during venipuncture.
Term
prealbumin physiology
Definition
a) tryptophan rich tetrameric glycoprotein
b) mainly synthesized in liver
Term
prealbumin function
Definition
serves as carrier protein for thyroid hormones (T3, T4) and vitamin A. Can also be used to asses nutritional status.
Term
clinical signif. of prealbumin
Definition
decreased in number of liver diseases due to impaired synthesis. Increased in ppl who are receiving steroids. Can also be synthesized by cells of choroid plexus.
Term
antibody
Definition
group of plasma proteins (immunoglobulins) that are produced by B lymphocytes due to exposure to an antigen. Reacts to a specific antigen.
Term
antigen
Definition
substance that stimulates antibody formation and has ability to bind to an antibody.
Term
phenylketonuria (PKU)
Definition
metabolic disorder in which there is genetic deficiency of enzyme phenylalanine hydroxylase
Term
maple syrup urine disease (MSUD)
Definition
autosomal recessive metabolic disorder in which there is genetic deficiency in enzyme that degrades branched chain amino acids. Results in accumulation of valine, leucine, and isoleucine in blood and associated keto acid metbolites in urine. Condition is characterized by poor feeding, vomiting, lack of energy, seizures, and mental issues.
Term
clinical signif. of maple syrup urine disease
Definition
leads to severe brain damage and may result in death. Variant forms appear later in childhood, typically less severe. Restrict food containing branched chain AA's leucine, isoleucine, and valine in food like milk, meat, and eggs. Diet must be adhered to strictly and permanently.
Term
hypoproteinemia
Definition
decrease in total serum protein levels in blood, especially albumin
Term
clinical signif. of hypoproteinemia
Definition
1) starvation/nutritional deficiency of essential amino acids
2) excessive loss in urine due to renal disease/poor absorption of AA's.
3) chronic liver disease
4) inflammatory conditions
Term
hyperproteinemia
Definition
increase in total serum protein levels in blood
Term
clinical signif. of hyperproteinemia
Definition
1) dehydration
2) increased synthesis of gamma globulins as would occur in acute phase response
3) measurement of unexpected protein such as fibrinogen
Term
porphyrias
Definition
group of diseases associated with hereditary and acquired deficiencies in heme biosynthetic pathway. Sufficient enzyme activity even in dysfunctional enzymes that will support heme biosynthesis. Accumulation of porphyrins that are toxic to tiss. in high concentrations. Symptoms and treatment are not all same, some are cutaneous in nature and will manifest on skin. Exposure to light can result in swelling, itchy skin, and fluid accumulation. aka photoporphyrias
Term
porphyrinuria
Definition
excessive excretion of 1 or more porphyrins in urine
Term
porphyrinemia
Definition
presence of porphyrin in plasma or serum
Term
porphyrin disorder (hereditary)
Definition
genetic disorders arising from impaired activity of enzymes in synthesis of heme
Term
porphyrin disorder (aquired)
Definition
More common form, from lead poisoning, chronic renal failure, iron deficiency, and liver disease.
Term
thalassemias
Definition
groups of inherited anemic diseases, most common genetic disorders in world. Derived from globin genetic mutations that result in little to none globin protein being produced. If alpha and beta chains are absent or in low levels then it affects Hb's ability to bind and transport oxygen. Conditions include enlarged spleen or requiring blood transfusions.
Term
sickle cell anemia
Definition
Hb S represents sickled RBC and is most common abnormal type of hemoglobin. Results from single mutation in beta globin gene that causes Hb structure to sickle under hypoxic conditions. If not managed, can be life threatening.
Term
caraminohemoglobin (CO2Hb)
Definition
compound of carbon dioxide and Hb, approx 70-85% of CO2 is processed as bicarbonate and expired from lungs. Approx. 10-20% of CO2 binds to each globin chain of Hb molecule.
Term
methemoglobin (M-Hb)
Definition
compound of Hb where 1 or more iron molecule is oxidized from ferrous state to ferric state. Oxidized iron can't bind oxygen. Levels are maintained at less than 1% by diff. enzyme systems found within RBC
Term
sulfhemoglobin (S-Hb)
Definition
green pigmented compound formed by addition of hydrogen sulfide molecule to Hb. Irreversible oxidation and conversion persists thruout life of erythrocyte. Appears after exposure to certain drugs or chemicals, or occupational exposure to sulfur.
Term
carboxyhemoglobin (COHb)
Definition
compound formed by binding of carbon monoxide to heme iron. Hb has 200 times greater affinity for carbon monoxide than oxygen. Carbon monox. creates stronger bond with Hb, because of this carbon monox. is released at exponentially slower rate than oxygen. Individuals poisoned by carbon monox. exhibit "cherry red" color.
Term
Cryoglobulin pathophysiology
Definition
abnormal globulins occasionally encountered in serum which can precipitate when serum is cooled to low temp. but re-dissolved when serum is rewarmed to body temp. (37 deg. C) Result of polymerization of immunoglobulins. Cryoglobulin complexes deposit on vessel walls causing inflammation. Vasculitis can lead to renal damage/neurological diseases
Term
clinical signif. cryoglobulin pathophysiology
Definition
frequently seen in myeloma, macroglobulinemia, and some autoimmune diseases.
Term
Structure of immunoglobins (Ig)
Definition
1)2 diff. polypeptide chains held together by disulfide bonds:
2 light chains, and 2 heavy chains

2)light chain; one variable domain and one constant domain

3)heavy chains; one variable domain, responsible for formation of specific antigen binding sites; and three constant domains, region of Ab that varies little within Ig class
Term
functions of immunoglobins
Definition
1) neutralize toxic substances
2)facilitate phagocytosis
3) kill pathogens, often by activation of complement system
4) combine with antigen on cellular surface and cause destruction of these cells either extra/intravascularly
Term
5 classes of immunoglobins
Definition
IgG, IgM, IgA, IgD, and IgE