BCH4024 Exam 1 Real

His 93

• Proximal

• On F8

His 64

• Distal

• E7

  • Rotates to open and close pocket where O₂ binds

α₁β₁ and α₂β₂ interaction

>30 residues

α₁β₂ and α₂β₁ interaction

19 residues

Hemoglobin is comprised of

8 alpha-helical globins

High affinity for oxygen (closed conformation)

R state

Low affinity for oxygen (open conformation)

T state

Neuroglobin

• Monomeric

• In neurons

  • Protects brain from hypoxia

Cytoglobin

• Monomeric

• Regulates NO levels

K_d

• Dissociation constant

• Low = good (strong binding)

• [P][L]/[PL]

Low pH effect on Hb

• Stabilized T-state (encourages release of O₂)

• Prefers binding to CO₂

Carbonic anhydrase

Catalyzes hydration of CO₂ to HCO₃^-

Bohr Effect

The effect that pH and [CO₂] have on binding and release of O₂ to Hb

2,3-Bisphosphoglycerate

• Stabilizes T-state

• Binds to a distant site from O₂ site (heterotropic allosteric modulator)

  • Very negatively charged

α2γ2 Hemoglobin

• Synthesized by fetuses

• Lower affinity for BPG

  • Higher affinity for O₂

Sickle cell anemia

• Caused by missense mutation in globin gene (Val⁶ instead of Glu⁶)

  • Beta subunits become hydrophobic and aggregate in the deoxy state

Regulatory enzyme function

Increase or decrease catalytic activity in response to a signal

(DOES NOT FOLLOW M-M KINETICS)

Regulatory enzyme position

First enzyme in a multistep pathway

Homotropic regulation

Substrate and modulator are identical

Heterotropic regulation

Modulator is a molecule other than the substrate

ATCase

• Catalyzes formation of carbamoyl aspartate (nucleotide precursor)

• Multisubunit

  • 12 polypeptide chains

  • 6 catalytic subunit

• ATP acts as positive regulator

  • Kicks out CTP

• CTP acts as negative regulator

  • Inactive when bound

Allosteric enzyme kinetics

• Sigmoidal saturation curve on M-M plot

• ½ V_max represents K_0.5, not K_m

• Small increase in [S] may correspod to a large increase in V₀

Heterotropic activator

Causes M-M curve of allosteric enzyme to become hyperbolic and shift left

K_0.5 decreases

Heterotropic inhibitor

Causes M-M curve of allosteric enzyme to become more sigmoidal and shift right

K_0.5 increases

Ser, Thr, Tyr, His

AA residues that kinases phosphorylate

Glycogen phosphorylase

• Converts glucose to glucose-1-phosphate

• Active when phosphorylated (phosphorylase a)

  • OCCURS AT SERINE

• Inactive when dephosphorylated (phosphorylase b)

• Regulated by:

  • Phosphorylase kinase

  • Phosphoprotein phosphatase 1

Zymogen

Inactive precursor (proprotein/proenzyme) cleaved to form an active protease

Blood clot

Aggregate of platelets cross-linked/stabilized by fibrin

Fibrin

Derived from fibrinogen (soluble zymogen)

Thrombin

Serine protease that proteolytically cleaves fibrinogen to fibrin

Factor XIIIa

Transglutaminase that catalyzes the formation of covalent cross-links between fibrin polymers

Intrinsic pathway

Involving all components of blood plasma (for internal wounds)

Extrinsic pathway

Pathway involving tissue factor (tf, not found in blood)

Catabolic

Converging metabolic pathways

Anabolic

Diverging metaboli pathways

Group transfer

Process that couples ATP hydrolysis with endergonic reactions

Phosphoryl

1 P_i group

Pyrophosphoryl

2 bound P_i groups (PP_i)

Adenylyl

AMP

MgATP^2-

True cellular substrate

Carbohydrate functions

• Structure

• Energy storage

• Protection

• Joint lubrication

• Cell-cell adhesion

• Cell-cell recognition

  • Cell transport signaling

Carbohydrate empirical formula

(CH₂O)_n

Heteropolymer

Polymer comprised of more than one monomeric unit

D stereoisomer

Most common isomeric form of sugars

Number of possible steroisomers

2ⁿ (where n = # of chiral centers)

Epimers

Two sugars that differ only in the configuration about one carbon atom

(“rotated” hydroxyl)

Pyranose

6-membered ring formed from reaction of C-5 with C-1 ALDEHYDE

Furanose

5-membered ring fromed from reaction of C-5 with C-2 KETONE

Hemiacetal/ketal

Reducing end of glycosidic bond

Starch

Storage carbohydrate comprised of amylose and amylopectin

Amylose structure

• Unbranched D-glucose chains

  • Connected by α1→4 linkages

Amylopectin structure

• Large

• α1→4 linkages between glucose residues

• α1→6 linkages in branches

Glycogen structure

• Only glucose subunits

• α1→4 linkages between glucose residues

• α1→6 linkages in branches (HIGHLY EXTENSIVE AND COMPACT)

Glucose residue configuration in cellulose

Beta configuration

Bonds between glucose in cellulose

β1→4 glycosidic bonds

Glycosyltransferases

Enzymes that assemble complex glycan chains via stepwise transfer of monosaccharide units from nucleotide-linked sugars

Glycoside

A molecule joined by a glycosidic bond

Lipid functions

• Energy storage

• Membrane structure

• Cofactors

• Electron carriers

• Light-absorbing pigments

• Chaperones

• Emulsifying agents

• Hormones

• Intracellular messengers

Oxidation

Releases energy stored in fatty acid C-C bonds

MUFA double bond position

Between C-9 and C-10

PUFA double bond position

Between C-12 and C-15

(often separated by a methylene)

Triacylglycerol

• 3 fatty acids

• 1 glycerol

• Linked via ester linkages

  • Simple or mixed

Types of phospholipids

• Glycerophospholipids

• Sphingolipids (e.g. sphingomyelin)

Types of glycolipids

• Sphingolipids, e.g.:

  • Glycosylceramide

  • Globoside

  • Ganglioside

• Galactolipids/sulfolipids

Types of membrane lipids

• Phospholipids

• Glycolipids

• Archaeal ether lipids

• Sterols

Glycerophospholipid/phosphoglyceride

• Glycerol + 2 fatty acid + PO₄

• Connected via ester linkages

  • Phosphodiester

Phosphosphingolipid

• Sphingosine instead of glycerol

  • Contributes a nonpolar tail

• 1 fatty acid

• 1 head group

Ceramide

H head group

Phosphocholine

Sphingomyelin head group

Glycosylceramide

Glucose head group

Globoside

1-4 carbon sugar head group (sphingolipid)

Often:

• D-glucose

• D-galactose

• N-acetyl-D-galactosamine

Ganglioside

• Complex oligosaccharide

• 1+ residue of Neu5AC at end

  • N-acetyl-D-galactosamine

Cerebroside

• Single sugar linked to ceramide

Galactose

Cerebroside sugar in neural plasma membrane

Glucose

Cerebroside sugar in non-neural plasma membrane

Archaeal tetraether lipid

Two long alkyl chains with a glycerol at each end

Hydrolytic enzymes

Genetic defects in these lead to an accumulation of gangliosides

Sterol

• 4-ring structure

• Polar head group

• Alkyl/nonpolar side chain

• Rigid

  • Nearly planar

Cholesterol

• Sterol

  • Can be used to produce steroid hormones

Phosphatidylinositol

• Regulates cell structure and metabolism

• Important for intracellular signaling

• Fatty acid sits in plasma membrane

• Head sits in cytosol

  • Proteins cleave phosphate groups from the head

Eicosanoids

Paracrine hormones that act locally (near the point of synthesis)

Eicosanoid functions

• Reproduction

• Inflammation/fever/pain

• Blood clot formation

• Blood pressure regulation

  • Gastric acid secretion

Classes of eicosanoids

• Prostaglandins

• Thromboxanes

• Leukotrienes

• Lipoxins

Inorganic Cofactors

Fe²⁺, Mg²⁺, Mn²⁺, Zn²⁺

Oxidoreductase

Transfer electrons (H or hydride)

Transferase

Transfer specific groups

Hydrolase

Facilitate hydrolysis (add or eliminate water)

Lyase

Cleave bonds by elimination or add groups to double bonds

Isomerase

Change isomeric form by transfering groups within molecules

Ligase

Form bonds via ATP (or similar)-coupled condensation reactions

Translocase

Move molecules/ions across membranes

Rate constant (k) units

M^(1-order)⋅s^-1

Steady state

Constant [ES] `

Equilibrium assumption

Second step is rate limiting, first goes to equilibrium

Steady-state assumption

[ES] is constant (ignore k_-2)

V₀ depends on…

[S]

Good K_m is…

Small

Good k_cat is…

Big

k_cat (turnover number)

Maximum number of substrate molecules an enzyme can convert to product per unit time

K_m

Measure of binding affinity