Quiz 2 Flashcards
Nonessential
Synthesized in the body; Alanine Asparagine Aspartate Glutamate Serine
Conditional Essential
Synthesis can be limited under special pathophysiological conditions (prematurity of infants or those with severe catabolic distress) Arginine Cysteine Glutamine Glycine Proline Tyrosine
Essential
Indispensible aa; can't be synthesized de non so must be supplied by diet Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine
ketogenic
AA that are converted to acetyl CoA or acetoacetate so precursors of FA and ketone bodies
Glucogenic
AA converted to precursors for glucose synthesis like alpha ketogluterate, succinyl coA, fumerate, pyruvate, oxaloacetate
Both ketogenic and glucogenic
Isoleucine, Phenylalanine, Tyrosine, Tryptophan, Threonine
Stereoisomerism in alpha- AA
L and D configurations ; most in nature are L
AA are all chiral except glycine (enantiomers)
Nonpolar, aliphatic R groups
Glycine, Alanine, Proline, Valine, Leucine, Isoleucine, Methionine
Aromatic R groups
Relatively nonpolar; absorb UV (Tryptophan absorbs most followed by tyrosine the Ph)
Tryptophan, Phenylalanine, Tyrosine
Polar, uncharged R groups
Serine, Threonine, Cysteine, Asparagine, Glutamine
Positively Charged R groups
Lysine, Arginine, Histidine
Negatively charged R groups
Aspartate, Glutamate
Reversible formation of a disulfide bond by the oxidation of 2 cysteine
Hair straightening (safer; most representative aa in hair)
Uncommon amino acids/ modifications of aa
Hydroxyproline and hydroxylysine found in collagen
Addition of phosphate, methyl, adenosine (reversible)
AA not found in proteins
Ornithine (urea cycle, bad breath) and citrulline (byproduct of production of nitric oxide- vasodilator)
Non-ionic or zwitterion forms of AA
Zwitterion- neutral molecules with a positive and negative electrical charge though multiple positive and negative charges can be present
a characteristic pH, called the isoelectric point (pI), the negatively and positively charged molecular species are present in equal concentration; characteristic pH at which the net electric charge is zero
Effects of chemical environments on pka
pka -COOH 1.8-2.4 [4.8?]
pka -NH3 8.8-9.7 [10.6]
isoelectric pt: 5.5-6.2
Titration of amino acids
pI=1/2 (pka1+pka2) of the pkas closest to each other? (+1, -1)
Proteins are polymers built from aa joined by peptide bonds
usually peptides- have ~50 or fewere AA vs proteins (1 or more polypeptide)
Formation of peptide bond by condensation
Removal of water (OH from carboxy and H from amine)
AA residues; not rotatable around peptide bond but can rotate around alpha carbon
As increase residues, increase of MW
Conjugated proteins
Lipoproteins, Glycoproteins, phosphoproteins, hemoproteins, Flavoproteins, metalloproteins
Levels of structure in proteins
Primary (aa string), secondary (alpha helix or beta pleated sheets; H bonds), tertiary (folding; polypeptide chain) quaternary (assembled subunits)
A change of a single aa can alter the function of protein
Ex. sickle cell anemia Glu–> Val
Collagen Synthesis
Need vitamin C (not enough OH without it- can’t attain full strength)
Hydroxyproline and hydroxylysine found in collagen
Diseases related to collagen
Scurvy, Osteogenesis imperfecta, Ehlers- Danlos Syndrome, Spondylopiphyseal Dyplasia
Elastin
highly elastic protein in CT; allows many tissues in body to resume their shape after stretching or contracting
Production of most plasma proteins occurs in the LIVER
Human serum albumin, osmolyte and carrier protein
α-fetoprotein, the fetal counterpart of serum albumin
Soluble plasma fibronectin, forming a blood clot that stops bleeding
C-reactive protein, opsonin on microbes
Acute phase protein
factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoproteins
The planar peptide group
Carbony O has partial neg. and amide N partial Pos. setting up small eltric dipole. All peptide bonds in proteins occur in trans configuration
alpha helix and beta pleated sheets
Alpha helix has cross linked disulfide bonds that make it tough, protective [alpha keratin of hair, feathers, nails]
Beta sheets can be parallel or antiparallel (H bonds are straight); soft/flexible [silk fibroin]
collagen triple helix (high tensile strength, without stretch); collagen of tendons, bone matrix
Pathways that contribute to proteolysis
process by which cells control the abundance and folding of the proteome, and consists of a highly interconnected network that integrates the regulation of gene expression, signaling pathways, molecular chaperones and protein degradation systems
Histones
Each chromosome consists of a single molecule of DNA complexed with an equal mass of proteins. Collectively the DNA associated with these proteins is called chromatin. Most of these proteins are histone; Have Arg and Lys bind phosphate groups (neg) form nucleosomes
Proteins denature and renature
Native state; catalysis active–> (addition of urea and mercaptoethanol) unfolded state, inactive (DISULFIDE cross links reduced to yeild Cys)–> Native, catalytically active state; disulfide cross links correctly reformed
Due to temp, pH
Quaternary structure
polypeptide chain (collagen) vs 2 beta and 2 alpha chains in Hemoglobin associated with Iron and Heme
Nervous System
Have 100 billion nerve cells (neurons) in human brain with each connected to ~10,000 others= 100 trillion nerve connections
CNS
Brain and spinal cord
PNS
Somatic (voluntary)
Autonomic (Involuntary)- Sympathetic (fight/flight, epinephrine) vs Parasympathetic (rest/digest, acetylcholine)
Neuron Morphology
Cell body (perikaryon, soma; has nucleus; metabolic and synthesis center), axon (myelinated, emerges from axon hillock [final site where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon]), dendrites
Dendrites
Typically short, small processes emerging and branching off the cell body; USUALLY COVERED WITH MANY SYNAPSES [PRINCIPAL SIGNAL RECEPTION AND PROCESSING SITE]; large number and extensive arborization of dendrites allows a single neuron to receive and integrate signals from many other nerve cells;
“changes in dendritic spines are of key importance in the constant changes of the neural plasticity that occurs during embryonic brain development and underlies adaptation, learning, and memory postnatally”
Axon
Conduct AP from cell body to synaptic terminal (allow rapid communication), most neurons have only one axon, typically longer than its dendrites, axonal processes vary in length and diameter (motor neuron axons innervate the foot muscles have lengths of nearly a meter)
Terminals (Boutons)- activated by transmitter and will shut down release and synthesis of Neurotransmitters
Astrocyte
most abundant CNS glial cell; star shaped, uptake of transmitters and potassium, produce growth factors and neuroactive factors, Help form the blood brain barrier, regulates interstitial fluid composition, provides structural support and organization to the CNS, assists with neuronal development, replicates to occupy space of dying neurons
Ependymal Cell
CNS glial cell; Epithelial like cells that form a single layer lining the fluid filled lines ventricles of brain and spinal cord, lining the ventircles of the cerebrum, columnar ependymal cells extend cilia and microvilli from the apical surfaces into the ventricles, assists in the production and circulation of cerebrospinal fluid
Microglial
CNS glial cell; not interconnected unlike the others, normally rare but common at sites of injury/ neurodegeneration, motile cells, constantly used in immune surveillance of CNS tissues, when activated by products of cell damage or by invading microorganisms, the cells retract their processes, begin phagocytosing the damage or dnager related material and behave as APCs, phagocytic cell that move through CNS, protects the CNS by engulfing infectious agents and other potential harmful substances
Oligodendrocyte
CNS glial cell; extend many processes, each of which becomes sheet like and wraps repeatedly around CNS axons, many are needed to cover entire length of axon, during wrapping, most cytoplasm gradually moves out of the growth extension leaving mutliple compacted layers of cell membrane called myelin; myelinates and insulates CNS axons, allows faster AP propagation along axon in CNS (myelin sheath electrically insulates axon and facilitates rapid transmission of nerve impulses)
Schwann Cell (Neurolemmocyte)
PNS glial cell; surround and insulate PNS axons and myelinate those having large diameters, allows faster AP propagation along axon in PNS
Schwann cells become aligned along axon and extend a wide cytoplasmic process to encircle it–> the spiral wrapping becomes compacted layers of cell membrane (myelin) as cytoplasm leaves the growing process
Gray vs White matter
Within brain and spinal cord, regions with tracts of myelinated axons compromise white matter while regions rich in neuronal perikarya (cell body of neuron with nucleus) and astrocytes compromise gray matter
Cell membrane
phospholipid bilayer; amphipathic
palmitate (16, saturated) and oleate (18,cis unsaturated)
unusual cell membrane
Archael bacteria (proks with no nucleus) have lipids with ether bonds instead of esters (bacteria/eukarya); opposite stereochemistry, branched chains
Biological membranes need to be fluid to allow proteins to move around and to respond to external deformations and damage. Likewise, they need to be impermeable to protons and other charged ions, to allow formation of EC gradient that powers life [lipids in our cells have these properties but only in a narrow range of temp]
Archael lipids form membranes with these properties over a wide range of temp. from freezing cold to boiling hot
selectively permeable membrane
size and charge affect the rate of diffusion: hydrophobic molecules (CO2, O2, N2)> small, uncharged polar molecules (H20, indole, glycerol)>large uncharged polar molecules (glucose, sucrose; can’t passively diffuse)> ions (lowest permeability, cant passively diffuse)
Different Membrane Proteins
Integral membrane proteins (embedded within; can’t be easily removed from bilayer without using harsh detergents that destroy it, float freely in bilayer; usually transmembrane- amphipathic)
associated membrane proteins (not directly attached; change in pH, chelating agent, urea, carbonate)
(GPI) anchor membrane proteins (phospholipase C cuts and get protein glycan)
peripheral (amphitropic) membrane proteins (easily separated from bilayer without harming it, less mobile within; biological regulation removes)
Each type of membrane has characteristic (dif composition/ concentration) lipids and proteins; and organelles also have them
Fluid Mosaic Model
Two-dimensional liquid in which phospholipid and protein molecules diffuse easily. The original model has been updated to account for membrane domains that restrict the lateral diffusion of membrane components (have special lipids and protein composition- lipid rafts; important for cell-cell signaling, apoptosis, cell division, membrane budding, and cell fusion)
Asymmetric Distribution of phospholipids in plasma membranes
lipids are associated differently from inside/outside; some cells on outside have more sphingomyelin receptors; signal transduction on inside
Distribution of Lipids in a typical cell
Golgi has different composition than trans goli network than transport vesicle (this one matches plasma membrane)
Transbilayer deposition of glycophorin (membrane spanning protein that carries sugar molecules ) in a RBC
N terminus outside and C terminus inside (most common?)
Integral proteins
Type 1 (carboxy in, amino out) Type 2 (amino in, carboxy out) Type 3 Type 5- transmembrane receptor/like a channel protein Type 7- single transmembrane
Lipid linked membrane proteins
different FA that attach them ex. GPI anchor on C terminus
Membrane Dynamics
2 extremes of lipid bilayer: liquid ordered state and liquid disorder state (heat produces thermal motion of side chains)
saturated need more energy to melt (increase melting point= S–>L) as well as longer length [dictate how membrane behave- fluidity]
In order to survive in low temp, need more oleic acid (18:1) than palmitric acid (16:0) to keep membrane fluid
Transbilayer movements require catalysis
Uncatalyzed transbilayer (flip flop diffusion)- very slow
Uncatalyzed lateral diffusion (very fast)
Catalyzed transbilayer translocation (ATP)- Flippase (p type ATPase, moves Pe and Ps from outer to cytosolic leaflet), Floppase(ABC transporter, moves phospholipid from cytosolic to outer leaflet)
Scramblase (moves lipids in either direction, toward equilibrium)
Movement of Proteins across membrane
plasma membrane is supported by cytoskeleton- assembly/disassembly during fusion
React cell with fluorescent probe to label lipids–> intense laser beam bleaches small area –>with time unbleached phospholipid diffuses into bleached area which shows lipids move in membrane
Membrane Microdomains
Lipid rafts are specialized membrane microdomains that compartmentalize cellular processes by serving as organizing centers for the assembly of signaling molecules, influencing membrane fluidity, and membrane protein trafficking, and regulating NT and receptor trafficking
Caveolins are a family of integral membrane proteins that are principal components of caveolar membranes and involved in receptor independent endocytosis. Act as a scaffolding (support) protein within caveolar membrane by compartmentalizing and concentrating signaling molecules; various classes of signaling molecules, including G- protein subunits, receptor and nonreceptor tyrosine kinases, endothelial nitric oxide synthase and small GTPases, bind Cav-1 through its ‘Caveolin scaffolding domain’
Solute Transport Across the Membrane
Simple Diffusion-nonpolar compounds only, down concentration gradient (passive)
Facilitated Diffusion- down EC gradient (passive)
Primary active transport- against EC gradient diven by ATP ex. Na/K ATPase
Secondary active transport- against EC, driven by ions moving down its gradient
Ion channel- down EC gradient, may be gated by ligand or ion (passive)
Ionphore- mediated ion transport down EC gradient
Simple diffusion without transporter requires more free energy than diffusion with transporter
CO2 in respiring tissues
CO2 produced by catabolism enters RBC–> Bicarbonate dissolves in blood plasma through chloride (goes in)- bicarbonate exchange (goes out)
CO2+ H20–> HCO3- H+ Cl- (carbonic anhydrase)
CO2 in respiring lungs
Bicarbonate enters RBC from blood plasma through
chloride (goes out)- bicarbonate exchange (goes in)–> CO2 leaves RBC and is exhaled
HCO3- H+ Cl- –>CO2+ H20 (carbonic anhydrase)
Types of transporters
Uniport
Cotransporters (Symport [same direction] or antiport [opposite direction])
ex. On apical membrane (facing intestinal lumen) have microvilli with 2 Na/1 Glucose symporter (drivent by high extracellular Na
On basal surface (facing blood) have 3Na (out)/ 2K (in) ATPase antiport AND have Glucose uniporter GLUT 2 (facilitates downhill efflux)
Membrane Fusion Events
Budding of vesicles from Golgi, exocytosis, endocytosis, fusion of endosome and lysosome, viral infection, fusion of sperm and egg, fusion of small vacuoles (plants), separation of 2 plasma membranes at cell division
Nervous System Overview
CNS (brain and spinal cord)
PNS (Cranial nerves and spinal nerves)–> somatic (voluntary; conscious) OR ANS (involuntary, subconscious)–> Sympathetic/ Parasympathetic
Neuron cell bodies receive input from dendrites, they send info via axons to other neurons or to target organs, axons degenerate due to damage and injury but can regenerate in the periphery, cell bodies last to die in injury and disease and rarely replaced in CNS
Spinal Cord Function
Relays info to and from brain, has local circuits (reflexes) and preserves segmental body plan (trunk/abdomen)
Spinal Cord Location
rostral extent- emerges from foramen magnum (hole in base of skull through which spinal cord passes)
caudal extent- ends between L1 and L2 vertebrae
In the developing fetus, L5 spinal cord and L5 nerve root location different because vertebral elements grow faster and further than spinal cord and nerve is dragged down with it (intervertebral foramen) - L5 spinal cord level is ABOVE L5 vertebrae, specifically around T12 /L1 level; cauda equina is around L5 vertebrae/nerve root
Vertebrae
Segmental organization of the vertebral column, vertebrae protect the spinal cord and support the body, spinal nerves emerge directly below their corresponding vertebrae, with one exception (don’t worry about coccygeal vertebrae)
C1-7 (transverse foramen), T1-12 (costal facets, spinous process protrudes down), L1-5 (huge body), S1-5 (all fused)
Spinal Cord Organization
segmental organization
7 cervical vertebrae, 8 cervical spinal levels, 8 spinal nerves; first spinal nerve emerges above C1 vertebrae, C8 nerve emerges below C7
12 thoracic vertebrae, spinal levels, and thoracic spinal nerves (nerve always emerges below vertebrae) [spinal cord located between T1 and T11 vertebrae)
5 lumbar vertebrae, spinal levels, spinal nerves (nerve always emerges below vertebrae) [spinal cord located between T11 and L1 vertebrae) Different growth IS NOW APPARENT
5 fused Sacral vertebrae, spinal levels, Spinal nerves (nerve always emerges below vertebrae) [spinal cord is located between L1 and L2 vertebrae]