Biochemistry Flashcards
Amino Acids: w/ non-polar, non-aromatic side chains (7)
Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline
Amino Acids: w/ Aromatic side chain, uncharged (3)
Tryptophan, Phenylalaline, Tyrosine
Amino Acids: w/ polar side chains (5)
Serine, Threonine, Asparagine, Glutamine, Cysteine
Amino Acids: w/ negatively charged, acidic side chains (2)
Aspartic Acid (aspartate), Glutamic Acid (glutamate)
Amino Acids: w/ positively charged, basic side chains (3)
Lysine, Arginine, and Histidine
Ionizable groups _____ protons under acidic conditions
gain protons
low pH tends to protonate groups
Ionizable groups _____ protons under basic conditions
lose protons
high pH tend to de-protonate groups
pka of carboxyl groups
2
pka of amino group
9-10
plane geometry of sp2 and sp3 hybridizations
sp2 bonds fall within the same plane
sp3 bonds do not fall within the same plane
Primary protein structure
linear (N term to C term)
stabilized by covalent bonds between adjacent amino aicds
Secondary protein structure
local structure, due to H bonding between near amino acids
alpha-helices and beta-pleated sheets
Tertiary protein structure
protein folding
determined by hydrophilic and hydrophobic interactions between R groups
and disulfide bonds
Quaternary Structure
not all proteins have this
aggregate multiple subunits, Hb
Purpose: reduce surface area, bring catalytic sites together
Enzyme Classifications (6)
LI'L HOT Oxidoreductases Transferases Hydrolases Lysases Isomerases Ligases
Oxidoreductases
catalyze redox reactions
reductant (e- donor) and oxidant (e- acceptor)
common names: “dehydrogenase” “reductase” “oxidase”
Transferases
catalyze movement functional group from one to another
“kinases” catalyze movement of phosphate group
Hydrolases
catalyze breaking compound into two using H2O
“phosphatase, nucleases, lipase”
[substrate]hydrolase, [substrate]ase
Lyases
catalyze cleavage of a single molecule into two products (without water)
can catalyze the reverse
“synthase”
Isomerases
catalyze rearrangement of bonds within a molecule (stereoisomers and constitutional isomers)
-Can be considered oxidoreductase, transferase, lyase, but NOT ligase
Ligase
catalyze addition or synthesis reactions
require ATP (all ligases require it)
[substrate] synthase, [substrate] synthetase
5 ways to reduce activation energy
- Transition state stabilization
- Microenvironment Adjustments
- Adjusting substrate proximity
- Transient Covalent bonding
- Reactant destabilization
Apoenzymes
enzymes without their cofactor
Holoenzymes
enzymes with their cofactor
Prosthetic groups
tightly bound cofactors/coenzymes necessary for enzyme function
Cofactors
inorganic molecules, metal ions, ingested dietary minerals
Coenzymes
small organic groups, vitamins, their derivatives
Water soluble vitamins
ascorbic acid (vitamin C) B complex vitamins
B complex vitamins (1,2,3,5,6,7,9,12)
1- thiamine 2- riboflavin 3- niacin 5- pantothenic acid 6- pyridoxal phosphate 7- biotin 9- folic acid 12- cyanocobalamin
Fat soluble vitamins
Vitamin A, D, E, K
Michaelis Menten constant
Km = velocity at 1/2 Vmax measure of E-S affinity faster enzyme (greater affinity) low Km
Types of Reversible Inhibitions
Competitive, noncompetitive, mixed, uncompetitive
Competitive Inhibition
occupies active site, inhibitor can completely block
-will be overcome by an increase in [S]
no effect on Vmax, increases Km
Noncompetitive Inhibition
bind to allosteric sites instead of active site (changes enzyme conformation)
do not compete for the same site, cannot be overcome by increase in [S]
decreases Vmax, no effect on Km
Mixed Inhibition
can bind to enzyme or E-S complex (different affinities)
binds at allosteric sites
changes Km depending on binding affinity
-if it prefers enzyme = increases Km
-if it prefers E-S complex = decreases Km
Uncompetitive Inhibition
bind only to ES complex, locks S in place and prevents release
decreases BOTH Vmax and Km
Irreversible Inhibition
- active site unavailable for prolonged period
- enzyme is permanently altered
- prime drug mechanism
- cannot reverse w/ removal of irreversible enzymes
Regulated Enzymes (3)
- Allosteric Enzymes
- Covalently Modified Enzymes
- Zymogens
Allosteric Enzymes
multiple binding sites
molecules binding to the allosteric site are either activators or inhibitors – causes a conformational change
Covalently Modified Enzymes
activated or deactivated by phosphorylations or dephosphorylation
Zymogens
some enzymes are quite dangerous, and are released in their inactive forms contain catalytic (active) domain and regulatory domain
5 Primary Structure proteins
- Collagen
- Elastin
- Keratin
- Actin
- Tubulin
Collagen
extracellular matrix of connective tissue, strength and flexibility
Elastin
Important component of extracellular matrix of connective tissue
fx. straighten/recoil like a spring
Keratin
intermediate filament proteins in epithelial cells
fx. mechanical integrity of cells (hair and nails)
regulatory protein
Actin
component of microfilaments and thin filaments in myofibrils
most abundant in eukaryotic cells
polarity = allows motor proteins to travel unidirectionally
Tubulin
component of microtubules – structure, chromosome separation, intracellular support
polarity
3 Motor Proteins
- Myosin
- Kinesins
- Dyneins
Myosin
primary motor protein
interacts with actin
thick filament in myofibril and cellular transport
Kinesins
motor protein associated with microtubules
2 heads remain attached to tubulin always = aligns chromosomes
Dyneins
associated with microtubules and 2 heads (one always attached to tubulin)
Cell Adhesion Molecules (CAMs) (3)
Cadherins
Integrins
Selectins
Cadherins
glycoproteins mediate calcium dependent cell adhesion
Integrins
extracellular matrix binding, signaling, promoting cell adhesion
Selectins
bind carbohydrate molecules, weakest type, expressed in cells that line blood vessels, vital role in inflammation and defense
Biosignaling: Ion channels
via Facilitated Diffusion
- Ungated channels: no gates (potassium channels)
- Voltage-gated channels: regulated by membrane potential change
- Ligand-gated channels: binding to channel causes it to open and close
Three primary protein domains (enzyme linked receptors)
Membrane-spanning Domain
Ligand-binding Domain
Catalytic Domain
Electrophoresis
using an electric field
proteins move according to NET charge and SIZE
(-) charge moves towards (+) anode
(+) charge moves towards (-) cathode
SDS-Page
disrupts all non covalent interactions = denature proteins
Mutarotation
if hemiacetal is in water = spont. cycle in open and closed form
IUPAC: Sucrose
glucose-alpha-1,2-fructose
IUPAC: lactose
galactose-beta-1,4-glucose
IUPAC: maltose
glucose-alpha-1,4-glucose
Sphingolipids (and 5 types)
structural lipids -backbone: sphingosine or sphingoid sphingophospholipids sphingomyelins glycosphingolipids gangliosides waxes
Sphingophospholipids
may also be phospholipid w/ phosphodiester bond
Sphingomyelins
contain phosphatidylcholine or phosphatidylethanolamine head group
-major component of myeline sheath
Glycosphinogolipids
attached to sugar not phosphate
cerebrosides = one sugar attached, globosides = two or more sugars attached
Gangliosides
oligosaccharides w/ 1 or more terminal N-acetylneuraminic acid
Waxes
long chain fatty acids “esterified” to long chain alcohols
two types of Signaling Lipids
Terpenes
Steroids
Terpenes
odiferous steroid precursors from isoprene
terpenoids: from terpenes via oxygenation or backbone rearrangement
Steroids
3 cyclohexane rings + 1 cyclopentane ring
steroid hormones: high affinity receptors (work event at low concentrations), gene expression and metabolism
Cholesterol
Prostaglandins
Fat Soluble Vitamins
Steroids: Cholesterol
steroid in membrane fluidity and stability
Steroids: Prostaglandins
autocrine and paracrine signaling, regulatory cAMP levels, effect smooth muscle contraction, body Temp, sleep/wake, pain, fever
Steroids: Fat Soluble Vitamins
A: Carotene = retinol for vision, retinoic acid = epithelial development
D: Cholecalciferol = calcitriol in kidneys, regulates Ca and P, promotes bone formation
E: tocopherols = antioxidants, aromatic rings that destroy free radicals
K: Phylloquinone + menciquinones = promote clotting factor
Purines
2 rings, Adenine and Guanine
Pyrimidine
1 ring, cytosine, thymine, uracil
Purine - Pyrimidine pairs
A – T
G – C
Helicase
enzyme, unwinds DNA generating 2 ssDNA templates ahead of polymerase
DNA topoisomerase
function in response to supercoiling introduce (-) supercoils
Start codon
AUG
Stop codons
UAA, UAG, UGA
DNA to DNA
replication (new DNA synthesized in 5’ to 3’ direction
template read 3’ to 5’
DNA to RNA
Transcription (new RNA synthesized 5’ to 3’ direction (template read 3’ to 5’)
RNA to Protein
Translation (mRNA read 5’ to 3’ direction)
“Wobble”
silent mutation tat affects the third base pair
protects against mutations
Three types of RNA in transcription
mRNA: carries DNA nucleus to cytoplasm to be translated
tRNA: brings aa in, recognizes codons on mRNA using anticodon
rRNA: ribosome, enzymatically active, synthesized in nucleus
Three metabolic states
- Postprandial state/Well-fed state
- Postabsorptive/Fasting state
- Prolonged fasting state (starvation)
Postprandial state/Well-fed state
blood glucose rises, stimulating insulin release
Postabsorptive/Fasting state
5 hours after food
counter regulating hormones: opposite effect of insulin on muscle, adipose tissue, liver
(Glucagon, Cortisol, Epinephrine, Norepinephrine, GH)
Glucogenolysis beings immediately, gluconeogenesis begins 12 hours later
Prolonged fasting state (starvation)
higher glucagon levels, lower glycogen levels
increase [glucose] via gluconeogenesis
levels of protein organization
1 = string 2 = alpha helices and beta pleats 3 = interactions, disulfide bridges, H bonding, hydrophobicity 4 = multiple sub units
Insulin in muscles does
entry of glucose
glycogen synthesis
protein synthesis
Insulin in adipose tissue
entry of glucose
triacylglycerol synthesis
Insulin in liver
glycogen synthesis
Insulin in nervous tissue
obtains energy via oxidation of glucose to CO2 and water during well fed/normal states
- grey matter: high glucose consumption
- white matter: low glucose consumption
Preferred fuel sources during well-fed and fasting state: liver
well fed: glucose, amino acids
fasting: fatty acids
Preferred fuel sources during well-fed and fasting state: Resting skeletal muscle
well fed: glucose
fasting: fatty acids
prolonged fasting: ketones
Preferred fuel sources during well-fed and fasting state: Cardiac muscle
well fed: fatty acids
fasting: fatty acids/ketones
Preferred fuel sources during well-fed and fasting state: adipose tissue
well fed: glucose
fasting: fatty acids
Preferred fuel sources during well-fed and fasting state: brain
well fed: glucose
fasting: glucose
prolonged fasting: ketones
Preferred fuel sources during well-fed and fasting state: RBCs
well fed: glucose
fasting: glucose
three types of cell-cell junctions
gap junctions
tight junctions
desmosomes
gap junctions
rapid exchange of ions and other small molecules
tight junctions
prevent paracellular transport
dont provide intercellular transport
desmosomes
and hemidesmosomes
-anchor layers of epithelial tissue together
three types of passive transport
- simple diffusion
- Osmosis
- Facilitated diffusion
two more important types of glucose transporters
GLUT 2 = low affinity transporter=high Km
-found in the liver for glucose storage
-and in pancreatic beta-islet cells as a glucose sensor
GLUT 4 = high affinity = low Km
-found in adipose tissue and muscle = stimulated by insulin
Glucokinase
- converts glucose to glucose 6-phosphate
- present in pancreatic Beta-islet cells (glucose sensor)
- responsive to insulin in the liver
Hexokinase
converts glucose to glucose 6-phosphate in peripheral tissues
Phosphofructokinas-1 (PFK-1)
- phosphorylates fructose 6-phosphate to fructose 1,6-biphosphate
- RATE LIMITING STEP
- stimulated by/activated by AMP and F 2,6-BP
- inhibited by ATP and citrate
Phosphofructokinase-2 (PFK-2)
- produces F 2,6-BP
- activates PFK-1
- activated by insulin
- Inhibited by glucagon
Glyceraldehyde-3-phosphate dehydrogenase
produces NADH
feeds into ETC
3-Phosphoglycerate Kinase (and pyruvate kinase)
- each perform substrate level phosphorylation
- places inorganic phosphate (Pi) onto ADP
NADH
produced in glycolysis
oxidized by mitochondria in ETC when O2 is present
If O2 and mitochondria are absent = NADH is oxidized by lactate dehydrogenase
two types of monosaccharides and their functions
Galactose = lactose in milk, trapped in cell by galactokinase, converted to glucose 1-phosphate via galactose-1-phosphate
Fructose = honey, fruit, sucrose, commonly trapped in cell by fructokinase, cleaved by aldolase B = glyceraldehyde + DHAP
Pyruvate Dehydrogenase
complex enzyme tat convert pyruvate to acetyl CoA
stimulated by insulin
inhibited by acetyl-CoA
Glycogenesis
glycogen synthesis using 2 main enzymes
- glycogen synthase: creates a-1,4-glycosidic links
- branching enzyme: creates a-1,6-glycosidic links
Glycogenolysis
breakdown of glycogen w/ 2 main enzymes
- glycogen phosphorylase: breaks a-1,4 link
- debranching enzyme: connects a-1,4 and breaks/releases the a-1,6 link
Gluconeogenesis
located predominantly in liver (but also cytoplasm and mitochondria)
- reverse of glycolysis
- three main enzymes that bypass irreversible steps
1. Pyruvate carboxylase
2. Fructose-1,6 Biphosphate
3. Glucose-6-Phosphate
Pentose Phosphate Pathway
“hexose monophosphate (HMP) shunt”
- located in cytoplasm
- generates NADPH and sugars
- rate limiting enzyme = glucose-6-phosphate dehydrogenase (activated by NADP+ and insulin, inhibited by NADPH)
5 enzyme complex that produces Acetyl-CoA
- Pyruvate Dehydrogenase
- Dihydrolipoyl Transacetylase
- Dihydrolipoyl Dehydrogenase
- Pyruvate dehydrogenase kinase
- Pyruvate dehydrogenase phosphatase
where does the citric acid cycle take place
in mitochondrial matrix
8 important enzymes of citric acid cycle
- Citrate Synthase
- Aconitase
- Isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase complex
- succinylcholine-CoA synthase
- Succinate dehydrogenase
- fumarase
- malate dehydrogenase
