uiowa biochem exam2 key concepts

monosaccharides exist in many isomeric forms

constitutional: same formula, different order

stereoisomer

- enantiomer: non superimposable mirror images

- diastereomer: differs at 2+ asymmetric carbons

-- epimer: differs at one asymmetric carbon

-- anomer: differs at asymmetric carbon in ring structure

cyclic monosaccharies

aldehyde+alcohol: hemiacetal

ketone+alcohol: hemiketal

cyclic glucose: pyranose

cyclic fructose: furanose

common modifications of monosaccharides

used for cell signaling, cell modifications on a cell surface

- methyl groups

- N acetyl groups

- N acetyl & glycerol

- phosphate

disaccharides and polysaccharides

common links:

alpha 1,4 bond

- glycogen and starch: cyclical structures with many links, storage form of glucose

alpha 1,6 bond

- glycogen and starch(?): glucose branching

beta 1,4 bond

- cellulose: makes a straight chain, structural roles

glycoproteins

carbs and proteins: lots of protein

- in cell membranes

proteoglycans

protein and glycosaminoglycan: lots of carbs

- structural/lubricant

glycosaminoglycan: disaccharide with amino sugar and negative charge (sulfates)

- chitin

mucins/mucoproteins

lots of carbohydrate

protein and N acetyl galactosamine

- lubricants

carbohydrate and protein attachment

N linkage: asparagine + carbohydrates= pentasaccharide core (3 mannose, 6carbon sugar, 2 N acetyl glucosamine/GlcNAc)

O linkage: serine/threonine + carbohydrate

lipid nomenclature

carboxyl terminal

- c2: alpha

- c3: beta

ratio of carbons:double bonds

carbon number, double bond number -enoic acid

methyl terminal

- c1: omega

lipid properties

soluble in organic solvents, not soluble in water

membranes, energy fuel

double bonds are usually cis (separated by a methylene)

decrease melting temperature by making a lipid more fluid: shorter & cis fatty acids

- prevention of tight packing and van der waals interactions

human bodies can't synthesize omega 3 fatty acids

triaglycerols

fatty acid storage (energy rich, hydrophobic)

- 3 fatty acids esterified to a glycerol

membrane lipids

phospholipids: major membrane lipids

- 1+ fatty acids linked to a platform, platform linked to a phosphate and alcohol

- glycerol phospholipid: phosphoglycerol

- sphingosine phospholipid: sphingolipids, myelin sheath

glycolipids: lipids with carbohydrates

- carbohydrates on outside of cell surfaces

- cerebrosides: simple

- gangliosides: complex, branched

cholesterol: steroid

- 3 cyclohexane ring and cyclopentane ring

- maintain membrane fluidity

- OH and hydrocarbon tail

phospholipids and glycolipids form bimolecular sheets

each layer is called a leaflet

amphipathic lipids self assemble because of hydrophobic sheets

- hydrophobic center and polar exterior

membrane fluidity: controlled by fatty acids and cholesterol

ordered lipids: solid like

disordered lipids: fluid like

- decrease fluidity: longer fatty acids

- increase fluidity: unsaturated fatty acids, increase temperature

- cholesterol "buffers" fluidity: disrupts solid-like lipids, but pushes fluid-like lipids

integral membrane proteins

anchored to membrane

transmembrane proteins have hydrophobic domains

peripheral membrane proteins

can dissociate from membrane with salt or pH (change in charge)

fluid mosaic model

membrane is a 2D that acts as a permeability barrier (ions and H2O) and a solvent (lipids and membrane proteins)

lateral diffusion

movement horizontally in a membrane

transverse diffusion

movement from one side of a membrane to another

primary active transporter

uses ATP to move molecules against concentration gradient

ex) Na+K+ ATPse pump: establish ion gradient

- ATP hydrolysis for movement of 2K+ and 3Na+

secondary active transporter

uses energy from movement of another molecule with concentration gradient to move another molecule against concentration gradient

- anti and symporters

ex) glucose move in with cell with Na+

passive transporter

with concentration gradient

- all uniporters (bind molecule to access the other side)

- some anti and symporters

pores and channels

with concentration gradient

- an opening in the membrane

- regulated (closed unless activated): ligand and voltage gated

ex) K+ channel starts off wide enough for K+ and H2O, narrows enough for K+

- ion specificity: selectivity filter that interacts with K+ only

- binds K+ tightly

signal transduction

1. signal released: primary messenger

2. reception of signal

3. transducers (secondary messengers) amplify and relay information

4. activators and effectors cause response

5. terminate signal

receptors and transmit of information

bind molecules outside the cell to cause signal inside the cell

7 transmembrane receptor

7 helices

bind a ligand: conformational change

activate G proteins (bind Pi for GDP-GTP)

ex) beta 2 adrenergic receptor

1. binds epinephrine

2. activated G protein (GTP)

3. GTP bound G protein activates adenylate cyclase

4. increase of cAMP (ATP to cAMP)

5. cAMP activates protein kinase A

heterotrimeric and monomeric G protein

inactive G protein: alpha subunit GDP, beta and gamma subunit

active G protein

GTPase activity: converts GTP to GDP

regulation: GAPs increase turnover of GTP to GDP

GEFs: dissociate GDP

cAMP, kinases, phosphatases

cAMP: activates PKA

kinases: transfer Pi from ATP to somewhere else

phosphatases: use water to cleave a phosphate group

dimeric receptor

1. ligand binding

2. causes dimerization

3. activation of a kinase

ex) GHR

1. binds ligand to tyrosine kinase (JAK2)

2. dimerization of receptors: cross phosphorylation of JAK2

3. phosphorylation of other proteins

dimeric receptor kinases

1. ligand binding

2. causes dimerization

3. activation of intrinsic kinases

ex) insulin signaling (i think)

1. insulin binds alpha subunit

2. dimerization of beta subunit: tyrosine kinase cross phosphorylation

3. phosphorylation of IRS binds PIP2

4. phosphorylation of phosphoinositide 3 kinase

5. PIP3 moves and activates PDK1

6. activates Akt with ATP phosphorylation

7. activates GLUT4 to increase glucose uptake

calmodulin regulation

calmodulin binds almost all Ca2+ in cell with EF hands

binds enzymes, pumps, protein targets

- CaM kinase: regulates cell ion permeability

- Ca2+ ATPase pump: restores cell to low Ca2+ after nerve impulse

disrupting signal transduction and disease

proto oncogene (normal) turns into oncogene (mutated)

Ras mutation can't hydrolyze GTP: active, cell proliferation

EGFR overexpression increases proliferation

mutated tumor suppressor genes: can't repress cell growth

digestion breaks large biomolecules into small precursors

small molecules processed into acetyl CoA (oxidized for ATP)

proteins denatured by low pH and hydrolyzed by proteases to produce amino acids and peptides

proteases break peptide bonds (pepsin) add H2O

carbs digested by alpha amylase (cleaves alpha 1,4 bonds in starch and glycogen), other enzymes convert polysaccharides into mono and disaccharides

maltase and alpha dextrinase for maltose and limit dextrin

lipids solubilized by bile salts and digested by lipases to produce fatty acids which are resynthesized into triaglycerol for transport by chylomicrons

stomach: emulsification

intestine: bile salts

lipases digest lipid droplets : micelles

fatty acids-triaglycerol-mix w/ proteins- chylomicrons

partially digested food triggers release of enzymes into intestines to complete digestion

hormones and processes: secretin is stimulated and increases bicarbonate forms pancreas to neutralize pH

CCK: increase digestive enzymes, increase bile salts

zymogens

inactive precursors of proteases

activated by protease digestion

ex) pepsinogen self activates at optimal pH to make pepsin

ex) enteropeptidase activates trypsin, trypsin activates others

caloric homeostasis

maintaining adequate but not excessive energy stores

- humans evolved when there was less food around

metabolism interconnected by many reactions

- energetically favorable pathways

- coupling unfavorable reactions with exergonic reactions will shift equilibrium and make favorable combined reaction

ATP is the universal currency of free energy

- 2 phosphoanhydride bonds: high energy

- hydrolysis: ADP or AMP

- electrostatis repulsion, resonance, hydration, entropy

oxidation of carbon fuels is the major source of cell energy

electron carrier act as intermediates during oxidation: accepts and donates electrons

metabolic pathways use common carriers

ATP: phosphate

NAD+: 2 electrons, and 1 H+ (accept in oxidation reactions)

FAD: 2 electrons and 2 H+ (accept in oxidation reactions)

NADPH: phosphate (anabolism reduction)

CoA: 2 carbon units

3 general mechanism to regulate metabolic pathways

1. amount of enzyme: regulated in response

2. catalytic activity: reversible allosteric control

- feedback inhibition: product inhibits enzyme

- feedforward: modification with anticipated results

- covalent modification

3. substrate accessibility: compartmentalization limits substrates

glycolysis oxidizes glucose to 2 pyruvate to generate 2 ATP and 2 NADH

stage one: activates glucose so it can be converted into 2 three carbon fragments

stage two: 2 ATPs created by oxidation of 3carbon fragments to pyruvate

glycolysis

1. hexokinase adds phosphate (prevents glucose escape)

- regulated, uses ATP

2. glucose 6-fructose 6

3. PFK adds phosphate to fructose for 1,6 biphosphate

- regulated, uses ATP

- irreversible, committed step

4&5. cleavage for GAP and DHP interconverted

6. glyceraldehyde 3 phosphate dehydrogenase

- GAP to 1,3 BPG

- redox reaction (aldehyde oxidation, NAD+ receives electrons, Pi makes ester)

- NAD+ to NADH

7) phosphoglycerate kinase: 1,3 BPG to 3 phosphoglycerate

- generates ATP! (direct phosphate transfer)

8) 3PG to 2PG

9) enolase: 2PG to PEP

10) pruvate kinase: PEP to pyruvate

- generates ATP! (direct phosphate transfer)

cells must balance redox potential during glycolysis

generating NAD+ through ETC

need to harvest electrons in times without oxygen

fermentation 1

pyruvate to ethanol

- generates 2 ethanol, 2 CO2, 2ATP from glucose

- NADH and H+ to make NAD+

-- no net reaction

fermentation 2

lactate

- generates 2 lactate and 2 ATP

- NADH and electrons - NAD+

- electrons donated to pyruvate to form lactate

-- no net redox

fermentation

no oxygen needed, less energy produced

aerobic respiration

needs oxygen, more energy

pyruvate to acetyl CoA and CO2

fructose and galactose in glycolysis

converted into intermediates

fructose: hexokinase phosphorylates fructose or fructose 1 phosphate pathway (phosphorylated and split into DHAP and G3P)

galactose: phosphorylated and activated by UDP-glucose, UDP galactose into UDP glucose

muscle glycolysis

PFK: regulated by ATP and AMP, pH decrease, citrate decrease

- increased activity at low ATP/AMP ratio

- committed step

hexokinases: product inhibition by G6P

pyruvate kinases: regulation by decrease in ATP, increase in F16BP

- feedforward stimulation by fructose 1,6 biphosphate

liver glycolysis

more constant ATP level than muscle

PFK regulated by ATP/AMP inhibited by citrate, activated by F2,6BP (increase affinity for fructose 6 phosphate: feedforward

hexokinase: product inhibition by G6P

- high [glucose] means G6P present, glucokinase

pyruvate kinase: regulation by decrease in ATP, increase in F1,6BP

- feedforward stimulation by fructose 1,6 biphosphate

glucose transporters link blood glucose level, glycolysis, insulin, secretion in beta cells

GLUT2 imports glucose when concentration high

stimulates glycolysis (increases ATP)

high [ATP] increases K+ and Ca2+ which promotes release of insulin

glucose is synthesized from non carbohydrate precursors in gluconeogenesis

glycolysis and gluconeogenesis have some common steps

3 irreversible steps in glycolysis

- hexokinase: glucose to glucose 6 phosphate

- PFK: fructose 6 phosphate to fructose 1,6 biphosphate

- pyruvate kinase: phosphoenolpyruvate to pyruvate

gluconeogenesis bypass

- glucose 6 phosphatase: glucose 6 phosphate to glucose

- fructose 1,6 biphosphatase: fructose 1,6 bisphosphate to fructose 6 phosphate

- pyruvate carboxylase: pyruvate + ATP to oxaloacetate and ADP

-- PEPCK: oxaloacetate + GTP to phosphoenol pyruvate + GDP

pyruvate to phosphoenolpyruvate

pyruvate carboxylase: adds CO2 with biotin cofactor

ATP activates bicarbonate: reacts with biotin to give CO2 biotin, CO2 to pyruvate to oxaloacetate to malate (move to cytoplasm)

oxidize malate in cytoplasm for oxaloacetate and NADH, carboxylation to phosphoenolpyruvate

cytoplasm

all enzymes in gluconeogenesis perform here except

pyruvate carboxylase: mitochondria

glucose 6 phosphatase: ER

glycolysis and gluconeogenesis are reciprocally regulated

more glucose: glycolysis

scarce glucose: gluconeogenesis

regulated reactions

fructose 1,6 biphosphate to fructose 6 phosphate

- +citrate, -AMP, -F2,3BP

pyruvate to phosphoenolpyruvate

- +acetyle CoA, -ADP

cell energy state

regulates fructose and PEP conversions

- citrate: citric acid status

- alanine and acetyl CoA indicate abundant precursors--- glycogen synthesis

F2,6BP activates PFK: increased affinity for fructose 6 phosphate, more active at high ATP (feedforward)

blood glucose regulation

F2,6BP regulated by phosphofructokinase 2 and fructose biphosphatase

cori cycle

liver: lactate to pyruvate

gluconeogenesis regenerates glucose for muscles

muscles: lactate to energy

- proteins-alanine-pyruvate-energy