BIOCHEMISTRY NOTES

Based on YouTube videos by Pass The Dental Boards + some online/book research + DD = THIS IS ALL YOU NEED TO KNOW ABOUT BIOCHEM!
Watch these videos & compare to the notes (not available in full anymore, but they might still help):
https://www.youtube.com/channel/UCbFkz1rgQUG7radni0iXCbQ/videos
Abbreviations: E – enzyme, [X] – concentration of substance X, e – electrons, MC – most common
There are some really stupid mneumonics, but whatever helps, right? ☺ Please, don’t feel offended. Print it out, I added important pictures at the end, it helps if you
are reading the notes and having a picture right next to you to compare different processes (for example, Krebs cycle picture with the notes). You have to read the file
MULTIPLE times, I don’t know how to do magic by remembering things after one read ;) I left some space at the end for your own notes, under the pictures.
Keep working hard, you got this!
Paulina

LIPIDS

1. Types
• Fatty acids (FA)
• Triglycerides (TG) = Triacylglycerols (TAG)
• Phospholipids
• Lipoproteins
• Sphingolipids

2. FATTY ACIDS
• 2 essential FA:
• Linoleic acid (18:2)
• -linolenic acid (18:3)
• Both can lead to production of: arachidonic acid (20:4) → prostaglandins (PG)
• Names
• 12C lauric acid
• 14C myristic acid
• 16C palmitic acid (palmitate)
• 18C stearic acid → 18:1 oleic acid (oleate) → 18:2 linoleic acid (linoleate) → 20:4 arachidonic acid
• 20C arachidic acid (often as a distractor!)
• MNEUMONIC for saturated FA (the ones “18:X” are unsaturated): Lauri, driving with MyWrist, change to palms to
steer, spider attacks!
• A girl named Lauri is driving a car with “my wrists” (her wrists), then changes to palms to steer the wheels
and all of the sudden a spider attacks = lauric, myristic, palmitic, stearic, arachidic

3. TAG
• Ester linkage; lipase via hydrolysis → FA + glycerol
• Adipose tissue

4. SPHINGOLIPIDS (glycolipids)
• Ceramide: simplest, parent molecule, X = H
• Cerebroside: X = glucose (glycolipid)
• Ganglioside: X = a bunch of sugars (glycolipid) Gang of sugars
• Sphingomyelin: X = choline accumulated in Niemann-Pick; yields sphingosine,
choline, FA, phosphoric acid
5. PHOSPHOLIPIDS
• 2 major types
• Lecithins = phosphatidylcholine (PC)
• Cephalins = phosphatidyletanolaine (PE)
• Lecithins: most common (MC) phospholipid in bilayer membranes; yields 1 glycerol, 1 phosphate group, 1 choline, 2
FA
• Choline:
1. Sphingolipid → sphingomyelin
2. Phospholipid → phosPHATidylocholine (PHAT = fat)
Both  in outer leaf membrane
o Choline has a lipotropic effect on fatty liver (helps metabolizing fat by exporting fat from the liver)
o Choline → betaine (metablolite) = importat in metylation
 6. LIPOPROTEINS
• Proteins =  dense
Fats =  dense
• Chylomicrons, VLDLs, LDLs, HDLs
• Chylomicrons from intestine
dietary TAG around body, dietary cholesterol to liver
• VLDL TG from liver to tissues
• LDL from VLDL
Highest cholesterol content
Receptor mediated endocytosis (familial hypercholesterolemia)
Delivery to all tissues especially liver
• HDL de novo in the liver
Receptor mediated endocytosis
Cholesterol esters from tissues to the liver

Epinephrine/glucagon:  blood free FA (→cells = energy) FIGHT OR FLIGHT

Insulin:  lipid synthesis +  blood FFA REST AND DIGEST

Bile salts
o Steroid → cholic acid + glycine/taurine → bile salts
o “+” stands for amide linkage
o 2 types: glycocholic acid, taurocholic acid (aka sodium taurocholate / glycocholate)
o Made in the liver, aid in absorption of FA
o 95% is recycled = Na+/bile acid cotransporter in the distal ileum

FATTY ACID SYNTHESIS

Malonyl-CoA
o Acetyl-CoA (2C) + CO2 (1C) → malonyl-CoA (3C)
o E: Acetyl CoA Carboxylase (regulated step of FA synthesis!)
o Regulator of -oxidation
o Inhibits carnitine acyltransferase 1
o Reaction:

ACC
o Makes malonyl-CoA (3C)
o Biotin (“buying a carbon = carboxylase”)
o Regulated step of FA synthesis = allosteric E = irreversible fate = commited step
o Turned ON by  [citrate] → Krebs Cycle: citrate + OOA → acetyl-CoA
Turned OFF by  energy

FA synthase
o 5 units
o ACP (acyl carrier protein)

Regulation
In the cytosol: glycolysis, FA synthesis
In the mitochondria: ETC, -oxidation, TCA

-oxidation vs FA synthesis: Cell’s energy:

-oxidation FA synthesis Energy state Starving Full
Energy NADH/FADH2 (get) NADPH (use) Starts with FA 1 malonyl-CoA + many acetyl-CoA
Redox Oxidation Reduction Ends with Many acetyl-CoA Palmitate
Where? Mitochondria (liver, muscle) Cytosol (liver) Redox cofactors NAD+, FAD NADPH
Shuttle Carnitine Citrate Inhibitors Malonyl-CoA  [FA],  Epinephrine,  energy

FATTY ACIDS BREAKDOWN

Happens in the liver and muscle, mitochondria

Shuttle: carnitine acyltransferase 1
o Regulatory enzyme of -oxidation
o Malonyl-CoA inhibits
o Outer membrane

The little sperm-looking thing is actually a FA travelling in a blood vessel. It gets into the liver cell and through a shuttle (red dot) into mitochondria to undergo
-oxidation. The shuttle is carnitine acyltransferase 1, notice is on the outer membrane.

Products of -oxidation 16 C FA → 8 x acetyl-Coa (2C) → TCA → NADH, FADH2, ATP → ETC

18 C FA → 9 x acetyl-Coa (2C)
Etc.

KETONE BODIES
 energy / sugar state differs from starving/fasting/diabetes mellitus = CITO! → feed the brain!

In low energy state OOA from the TCA cycle is used up in gluconeogenesis to produce glucose.
In starving mode, the intermediates of the TCA cycle were used to produce glucose, so the acetyl-CoA can’t enter the TCA (it would get stuck in there, nothing to react
with is left). Instead, it is use to made ketone bodies, which the brain can use as an energy source.
Below the diagram you can see the three ketone bodies.
Ketone bodies:
o Made in the liver, mitochondria
o For brain in starvation state, RBCs can’t use them (no mitochondria)
o HMG-CoA synthase (regulatory enzyme, only in the liver)

Production of KB:

Ketogenic AA
o Ketogenic aa → actetyl-CoA → ketone body
o L + L = exclusively ketogenic (Leu, Lys)
o PhITTT = both gluco- & ketogenic (Phe, Iso, Tyr, Trp, Thr)

CARBOHYDRATES

Glycosidic bonds

Anomeric carbon:
o Sugars can be in a linear or ring form
o Anomeric carbon is the carbon bonded with two oxygens
o If a carb has free anomeric carbon, it is a reducing sugar
o Most mono- and disaccharides have anomeric carbons and are reducing sugars except sucrose (sucrose sucks!)

Fructose = free anomeric carbon, so it’s a reducing sugar.

Sucrose = anomeric carbon tied up in glycosidic bond, aka not “free” anomeric carbon, so it’s NOT a reducing sugar.
Reducing sugars:
- can donate electrons (aka reduce stuff)
- convert Cu2+ to Cu+
- reducing agents get oxidized and oxidizing agents get reduced
- because the reducing groups of both glucose and fructose are involved in the glycosidic bond, sucrose is not a reducing sugar

Monosaccharides: glucose, fructose, galactose (all are reducing)

- aldose (aldehyde functional group) vs ketose (ketone functional group)
- can be L or D variants: most sugars are D – glyceraldehyde
ALL (Aminoacids - L configuration) of us want to be DDS (D - sugars configuration)

Disaccharides = glycans
- many sugars linked by glycosidic linkages
- used for storage (glycogen) and structure (cellulose)
- types: starch, glycogen, dextrans, levans (fructans), GAGs

Starch
- a bunch of glucose joined by glycosidic bonds
- 2 enzymes to chew it: salivary & pancreatic amylase
- 2 types

Glycogen
-  1,4: linear, more common
-  1,6: branching (one in 12 glucose residues)
- most carbs in the body are stored as glycogen
- liver glycogen → maintains blood glucose
- muscle glycogen → provides glucose during exercise

Dextrans
- polysaccharides of glucose, but synthesized from sucrose (glucose + fructose)
- forms glycocalyx capsule in S. mutans
- sticky plaque: dextrans and levans

Levans (fructans)
- polysaccharides of fructose
- made from sucrose (g + f)

GAGs – they build proteoglycans

- unbranched polysaccharides that are repeating disaccharides (hexosamine + uronic acid)
- highly negatively charged (GAGing is negative)
- important structural component of ECM in CT (extracellular matrix in connective tissue)

Why perfect for ECM?

- mucous-like
- viscous-like
- has many “-OH” groups that attracts water
Examples
▪ Chondroitin sulfate
o Most abundant GAG of ECM (chondro = cartilage is abundant)
o Cartilage, tendons, ligaments
▪ Hyaluronic acid
o Exception: unique, because it contains NO SULFUR & it is NOT LINKED TO A PROTEIN
o Synovial fluid, vitreous humor
o Hyaluronidase destroys it
▪ HEparin
o  largest proportion of sulfate
o Anticoagulant (HEmorrhage)
o Exception: only intracellular GAG – mast cell granules
o Prevents formation of thrombin
o Mimics vit. K deficiency (vit. K is used to make thrombin)
▪ Heparin sulfate: basement membrane
▪ Dermatan sulfate: skin
▪ Keratin sulfate (keratosulfate): cornea, bone

Polymers
- dextrans: polymers of glucose made from sucrose
- levans: polymers of fructose made from sucrose
- glycogen: polymers of glucose made from glucose
- GAGs: repeatind disaccharides

Sucrose is cleaved by sucrase (invertase) into glucose and fructose.

Saccharin is a sweetner (Nutri-sweet)

O-glycosidic bonds → polysaccharides

N-glycodidic bonds → glycoproteins, nucleotides

PROTEINS

Peptide bond = amide bond

Polypeptide: 10+ AA
Protein: 100+ AA
N terminus – C terminus = NH3 – VAL – GLY – CYS – GLU – ALA – COOH
II structure: hydrogen bonds;  helix,  sheet,  turns (PRO is responsible for the turns)
III structure: hydrogen bonds, hydrophobic interactions, disulphide bonds (cysteine – cysteine sulfur bonds)

Denaturation breaks all bonds except peptide bonds (= unfolds the protein chain).
Protease cleaves peptide bonds.

Lab questions
- X ray diffraction: best to describe 3D structure of the protein
- electrophoresis: separates proteins based on the size and charge (depends on net electrostatic charge of a protein)
- ultracentrifugation: separates proteins weight on size by spinning

Collagen
- Gly 33% (same for elastin)
Gly-X-Y (Gly-Pro-HydroksyPro)
- Pro ( turns)
- Ala
- Hydroxyproline, Hydroxylysine – used to determine collagen content
Lysyl hydroxylase
- requires vit. C to work
- vit. C is a cofactor required for hydroxylation of Pro and Lys
- deficiency of vit. C = scurvy (pirates, bleeding gums, limes)
- poor collagen formation = poor wound healing and weak capillaries

Molecular weight of collagen is very large

- trihelical structure
- most abundant protein (by weight) in the body – album is most abundant in the blood serum

On the left side – collagen protein structures (where they are made)

Elastin
- a CT, 1/3 Gly, tropoelastin = similar to collagen
- rubber band/stretchy – collagen is tensile
- why is it stretchy? → no covalent bonds
- bonds: Lys crosslinks → not disulfide bonds which are strong covalend bonds

Albumin: simple protein, transporters (most Ca2+ is transported that way), oncotic pressure (colloid osmotic pressure), egg white

Transferrin: plasma, transports Fe

Cytochromes = protein + heme (porphyrin ring) + metal (Fe2+ and Fe3+)

- ETC (inner mitochondrial membrane)
- single unit – cytochrome C
- complexes – ubiquinone / CoQ / complex III
AMINO ACIDS

5 groups of AA:
▪ Non-polar, aliphatic R group – carbons, hydrogens
o Gly, Ala, Val, Leu, Met, Iso
o Polar bear can’t do meth
▪ Aromatic R group – ring structure
o Phe, Tyr, Trp
o “TYRe (tire) is ring shaped” = “It’s PHEny (funny), when you TRyP (trip) on a TYRe (tire)”
▪ Polar, uncharged R group – oxygen, nitrogen, sulfur
o Ser, Thr, Cys (disulphide bonds), Pro, Asn, Gln
▪ “+” charged
o His, Arg, Lys
o “Basically (+), the history of Argentina is a lie”
o Basically (+), aunt LYS was telling us a HIStory of ARGentina
▪ “-“ charged
o Asp, Glu (aspartic acid, glutamic acid)
o “Ass and gluts too, big → can’t fit into jeans → it’s negative”

Ketogenic vs. glucogenic

Ketogeic AA → acetyl-CoA → KB
L and L are exclusively ketogenic: Lys & Leu (Liz and Lucy like K-tones)
5 AA are both: PhITTT: Phe, Iso, Tyr, Trp, Thr

AA breakdown, for energy →  keto acids: pyruvate, oxaloacetate,  ketoglutarate

Most AA are L configuration (sugars are D)

“ALL of us want to be DDS”

Ser and Thr are not transaminated

“SERena (Williams) and THoR are not trans!”
Deamination: Ser → pyruvate
Dehydratation: Thr → propionyl-CoA

Nitrogen balance = intake – loss

Intake: how much you earn
Loss: how much you spend

Essential AA
- 9/10 (if we count Arg for babies growth)
PVT TIM HALL
Phe Trp His
Val Iso Arg
Thr Met Lys
Leu
- complete protein = contains all AA that are essential
- phenyloketonuria: tyrosine is an essential AA. They can’t eat Phe, which is a precursor of Tyr (add -OH), so their body can’t make Tyr
from scratch either.

Sulfur side chains

- Cys
- Met (thio-ester bonds)
- S-S bond is a disulphide bond, important in proteins
Non-polar R groups

- Gly
- Leu
- Iso
- Val
- Ala
- Met

Fist 5: pyruvate makes them

LIVA PY (Liver Pie): Leu, Iso, Val, Ala

ALANINE
- R group is a methyl group (gas)
- ALAn has gas after eating LIVA PY (liver pie) → ALA is made from pyruvate & it is a gas

Pyruvate + glutamate → alanine +  ketoglutarate

E: transaminase
Coenzyme: B6 = PLP = pyridoxal phosphate

GLYCINE
- only AA that is not chiral
- bile salts → glycocholic acid = cholic acid + glycine
- collagen, elastin = 33% glycine
- precursor to creatine, purines, porphyrin = Gly creates pure pores

VALINE
- Leucin and Valin are found in interior of globular proteins

N-X-X-X-X-X-G = good
N-X-X-X-X-X-V = very sick
Sickle cell anemia caused by Val substitution for Glu in 6th AA from N terminal chain of Hb  chain.

METHIONINE
- thio-ester
- encoded by start codon AUG

Aromatic R groups

Phe → Tyr → Dopa / Epi / NorEpi / thyroid hormones

Phenyloketonuria: tyrosine is not an essential AA, but with patients with that disease it is.

Tyrosine → L-Dopa → Dopamine

Phe → Tyrosine → L-Dopa → Dopamine → NorEpi → Epi

Polar, uncharged

SERINE
- the lipids phosphatidyloethanolamine and phosphatidylserine are more concentrated on the cytoplasmic face of the plasma
membrane
- has an “-OH” group that participates in enzymatic reactions: proteases → chymotrypsin, trypsin

Ser and Thr → phosphorylation in histones → replication

Lys → acetylation → transcription

Negatively charged
GLUTAMATE:
- excitatory neurotransmitter (GABA is inhibitory NT)
- I’m pumped! Today at the gym glutes, mate!

ASPARTATE
- one of two nitrogen sources in urea cycle

ENZYMES

General properties
- accelerate reactions: lower activation E to  rate of reaction
- specificity: active sites
- regulation: allosterism, competitive inhibition
- amplification of initiating signal: G protein cascade

Km (specificity constant) = enzyme stickness

• Km1 = 10-8
o Lower number = greater affinity, more sticky
o More specific – will bind only triangles
• Km2 = 10-2
o Higher number = lower affinity, less sticky
o Less specific – will bind triangles and squares

Michaelis-Menten equation measures velocity of enzymes

Km
- concept = affinity of enzyme for substrate aka stickiness
- lower number → greater affinity, more sticky
- higher number → lower affinity, less sticky
- math: [S] (substrate concentration) at ½ of Vmax
- note: Km is a measure of [S] units of molarity of moles/liter, NOT a measure of velocity!

Vmax = velocity of an enzyme at converting substrate to product when enzyme is saturated.

Lineweaver Burke plot: like a inverse Michaelis-Menten equation (aka double reciprocal plot)
• Y intercept is used to find Vmax
• X intercept is uded to find Km

Inhibition
- competitive - non-competitive
- uncompetitive - irreversible
3 things to know: does the inhibitor binds to the same active site? Km  or ? Vmax?

Km Vmax Active site

Competitive  - Same
Non-competitive -  Different

Competitive inhibition
- Km increased
• Need more [S] to reach ½ Vmax
• Add more [S] to overpower inhibitor

Non-competitive inhibition
- inhibitor can bind to 2nd active site
• Allosteric E – a regulator that binds to 2nd active site
-  Vmax: if you are not competitive you slow down

Irreversible inhibition
- suicide inhibition
- aspirin (inhibits COX-1 & COX-2 E), penicillin

Uncompetitive inhibition
- binds to ES complex
-  Km &  Vmax
Allosteric regulation
o A molecule that binds an enzyme (not an active site!) to regulate it up or down
o Regulator triggered by concentration
o High [ATP]: allosteric regulation will downregulate production of ATP
o Low [ATP]: allosteric regulation will up regulate production of ATP
o Phosphorylation and ATP can be allosteric regulators
o Non-competitive inhibition is a type of allosteric regulation
o Allosteric enzymes do not follow Michaelis-Menten kinetics

Zymogen: inactive, “baby” enzyme

Tripsinogen → trypsin
Pepsinogen → pepsin

Phosphatase vs. kinase

▪ Kinase is an enzyme that adds phosphates (phosphorylation) to things (ATP-ase in ETC, ADP → ATP)
▪ Phosphatase is an enzyme that removes phosphates (dephosphorylation)
▪ Covalent modification of an enzyme
▪ Alkaline phosphorylase and pyrophosphatase play role in calcification (teeth during development)

The regulation of metabolic processes is achieved through 2 mechanisms acting directly on enzymes: allosteric regulation & covalent
modification.

KREBS CYCLE

➢ Krebs cycle = tricarboxylic acid cycle (TCA) = citric acid cycle

➢ Occurs in the mitochondrium
➢ Final step of fat metabolism done by the TCA
➢ Question types:
o Counting carbons
o Intermediate names
o Enzyme names
o Inhibitor/regulation
o Energy yields
o ETC
Counting carbons
- starts with (4C) oxaloacetate + (2C) acetyl-CoA to make citrate
- (4C) oxaloacetate + (2C) acetyl-CoA → (6C) citrate
Krebs cycle starts with condensation of OAA and acetyl-CoA

Intermediate names
Citrate Is Krebs Starting Substrate For Mitochondrial Oxidation
Citrate Citrate
Is Isocitrate
Krebs -ketoglutarate
Starting Succinyl-CoA
Substrate Succinate
For Fumarate
Mitochondrial Malate
Oxidation Oxaloacetate

Intermediates
• OOA (OxalOAcetate)
o OOA + acetyl-Coa = first step
o Aspartic acid  OOA OO nice Ass
o Aspartic acid is the most immediate source of OAA during metabolism
• Acetyl-CoA
• Citrate
• -ketoglutarate: isocitrate dehydrogenase produces it
• Acids: OOA, -ketoglutamic acid

Enzymes
Citrate Citrate E: citrate synthase
Is Isocitrate E: aconitase OUT: CO2 + NADH
Krebs -ketoglutarate E: isocitrate dehydrogenase OUT: CO2 + NADH
Final step of fat metabolism! Rate-limiting step!
Starting Succinyl-CoA E: -ketoglutarate dehydrogenase OUT: GTP + CO2
Substrate Succinate OUT: FADH2
For Fumarate E: succinate dehydrogenase
Malonate inhibits! In ETC & TCA!
Mitochondrial Malate OUT: NADH
Oxidation Oxaloacetate

Succinate dehydrogenase
- malonate inhibits: “it succs that malonate can turn off the TCA”
- only E in both TCA & ETC
- in ETC part of complex 2

Isocitrate dehydrogenase
- rate-limiting E of Krebs cycle
- makes -ketoglutarate

Inhibitor/regulation
• Malonate = competitive inhibitor of succinate dehydrogenase (can be overcome with succinate)
• Malonyl-CoA → -oxidation shot blocker
• Malonate → Krebs cycle

Energy
3 NADH + 1 FADH2 + 2 CO2 + 1 GTP per acetyl-CoA = ~ 12 ATP
1 NADH = 3 ATP
1 FADH2 = 2 ATP
Glyoxylate cycle
- variations of Krebs cycle in plants & bacteria
- replenishes TCA intermediates (anaplerotic reactions)
- acetate (acetyl-CoA) is the main substance that bacteria use in the glyoxylate cycle

LOOK AT KREBS CYCLE PICTURE!

ELECTRON TRANSPORT CHAIN

“OIL RIG” Oxidation is loss

Reduction is gain

Location: inner membrane of mitochondria

In real life: 30-32 ATP
ATP: 2,5 for 1 NADH
1,5 for FADH2
FMN: riboflawin
NAD+: niacin

All about electrons:

• Made up of 4 electron carrying complexes (cytochromes)
o Electron source is NADH and FADH2
o Transfer of electrons (H+)
o Moved across inner membrane to the space between the inner and outer membrane
• Final step in aerobic generation of ATP
• Final electron acceptor is oxygen (H+ plus O2)

Major players: name, electron source, redox, Krebs cycle

Complex 1 = NADH dehydrogenase complex
Complex 2 = succinate dehydrogenase
- receives e from FADH2 / succinate
Complex 3 = coenzyme Q – cytochrome c reductase
Complex 4 = cytochrome c oxidase

Minor players
▪ Coenzyme Q (CoQ) aka ubiquinone
o Lipid that participates in ETC
o Electron carrier (receives from NADH, FADH2/succinate)
o CoQ is not derieved from vitamin (body synthesized it)
▪ Cytochromes (contain heme)
o Protein + heme
o Electron carriers (only e!)
 o Monomeric protein = cytochrome c
o Subunits of larger proteins (ex. complex 3 and 4)

Energy math
1 NADH → 3 ATP
1 FADH2 → 2 ATP
One glucose → 36-38 ATP

Complex I
CoQ Complex III Complex IV (cyt c)
Complex II

ATP synthase action: pumps protons from intermembrane space to matrix, produces ATP.

Overall reaction:
2H+ + 2e + ½ O2 → H2O + energy

PENTOSE PHOSPHATE PATHWAY (PPP)

• NADH
• Ribose sugars (DNA precursors)
• Ribose-5-phosphate / ribulose-5-phosphate (for nucleotides synthesis)

Occurs in:
- cytoplasm
- 2 phases 1. Oxidative → NADPH
2. Nonoxidative → 5 carbon sugars

NADPH uses:
- FA synthesis
- cholesterol synthesis
- ribose / deoxyribose interconversion
- NOT GLUCONEOGENESIS

PPP occurs in tissues carrying FA synthesis or cholesterol synthesis: mammary glands, adipose tissue, liver, adrenal cortex, also cornea
(high O2 partial pressure).
Minimal activity in brain tissue and nucleus.

Inhibition: regulated E – glucose-6-phosphate dehydrogenase (1st step); NADPH regulates E up and down

Summary:
▪ Aka pentose shunt, hexose monophosphate shunt, phosphogluconate pathway
▪ Major role: synthesis of NADPH and pentose (especially D-ribose to make nucleic acid)
▪ Can produce 5 carbon sugars (“pent” = 5!): used for DNA and RNA
▪ Occurs in cytoplasm

Purines → uric acid (urate) E: xanthine oxidase

 urate in GOUT
GLYCOLYSIS

Question types:
- stages of glycolysis
- carbon counting
- fates of pyruvate
- specific E
- Cori Cycle
- energy math

Occurs in cytoplasm
1 glucose = net 2 ATP and 2 NADH
6 carbons (glucose) → 2 x 3 carbons (pyruvate)

2 stages:
• Energy use phase
o ~ 2 ATP in step 1. and 3. “Babies eat most food at age 1. and 3.”
o Step 1.: hexokinase & glucokinase in the liver
o Step 3.: PFK (rate limiting E)
• Pay off phase
o + 4 ATP
_____________
Net 2 ATP per glucose

Main fates of pyruvate

Secondary fates of pyruvate

“Alan eats OX Pye (pie)”: Alanine, OOA  Pyruvate

Fates of pyruvate
➢ Lactic acid
o Lactate dehydrogenase
o Cori cycle
o Lactic acid fermentation
➢ Ethanol
o Yeasts
o Alcohol fermentation
➢ Acetyl-CoA
o Pyruvate dehydrogenase in mitochondria
➢ OOA
o Gluconeogenesis
o “Alan eats OX Pye (pie)”
➢ Alanine
o “Alan eats OX Pye (pie)”
 Product Enzyme Type Function
Lactic acid Lactate dehydrogenase Reduction Anaerobic
Acetyl-CoA Pyruvate dehydrogenase Oxidation Mitochondria, TCA, FA synthesis
Ethanol Reduction Anaerobic (yeasts)
OOA Pyruvate carboxylase Carboxylation Krebs cycle
Alanine Alanine aminotransferase Transamination Make AA

Carbon counting:
▪ Start: glucose
▪ After step 1.: Glucose-6-P (G6P)
▪ After step 2.: Fructose-6-P (F6P)
▪ After step 3.: Fructose-1,6-bisphosphate (F-1,6-P)
▪ After step 4.: Glyceraldehyde-3-phosphate + dihydroxyacetone phosphate (DHAP)
▪ After step 5.: (2) Glyceraldehyde-3-phosphate
o After step 6.: (2) 1,3-bisphosphoglycerate
▪ After step 7.: (2) 3-phosphoglycerate (3-PG)
▪ After step 8.: (2) 2-phosphoglycerate (2-PG)
▪ After step 9.: (2) phosphoenolopyruvate (PEP)
▪ After step 10.: (2) pyruvate

Which step do we go from 6 to 3 carbons? Step 4.

Step 3.: PFK

• Rate-limiting step
• Commited/irreversible
• Uses ATP
• Allosteric enzyme
o Allosteric modulation  by  [AMP]/[ADP] & fructose-2,6-bP;  by  [ATP]/[citrate] & H+
o To help always ask, what does it make? What is the energy state?
• Not associated with a membrane (occurs in the cytoplasm)
• ATP is substrate, but ATP will also inhibit = allosteric inhibition

Citrate review
❖ Kreb’s cysle: intermediate
❖ Glycolysis: inhibits PFK
❖ FA synthesis: citrate shuttle

Step 4.: Aldolase

➢ Converts 6 carbons to 3 carbons
➢ (6C) Fructose-1,6-bisphosphate

(3C) Glyceraldehyde-3-phosphate (G3P)
+
(3C) Dihydroxyacetone phosphate (DHAP)

“ALDO shoe brand – 2 shoes in a pair = 2 products”

Step 6.: G3P dehydrogenase

✓ Makes ATP

Step 7.: Phosphoglycerate kinase

✓ Makes ATP

Step 9.: Enolase

o 2 PG → PEP
o Sodium fluoride inhibits enolase, resulting in inhibition of glycolysis in oral bacteria = preventing caries
Step 10.: Pyruvate kinase
• makes 2 x pyruvate

NOTE!
Pyruvate → acetyl-CoA E: pyruvate dehydrogenase
This happens in mitochondria – not cytosol. This is NOT a part of glycolysis.

Lactic acid fermentation

Fermentation fact
o pyruvate reduced to lactic acid (OIL RIG)
o lactic acid is a byproduct of bacterial glycolysis (cariogenic)
o final e acceptor is organic compound (ETC is inorganic – O2)
o bacterial glycolysis
o 2 lactic acid and 2 ATP per glucose
o During exercise, low O2, muscles get energy via fermentation (Cori Cycle)

Cori Cycle
- recycling lactic acid by muscles during anaerobic
- recycling lactic acid (muscle) to glucose (liver) and skipping glucose back to muscle

GLUCONEOGENESIS

Intro:
- goal: glucose production
- 11 steps, 4 are different from glucolysis
- pyruvate →→→ G6P → glucose

Location: mostly in the liver (~90%), kidney (10%)

Job of the liver: make glucose and maintain glucose levels. Liver is like a mom of the body – it makes sure all the other organs and
tissues are fed.
Muscles lacks glucose-6-phosphatase, so what is the point of going through gluconeogenesis, if no glucose can be made after all?

Glucose-6-phosphate
o Last step of gluconeogenesis: G6P → glucose
o Glucose-6-phosphatase (liver and kidney, not muscles) – in gluconeogenesis & glycogenolysis (when we need glucose)

Important steps:
1) Pyruvate → OOA
• Fate of pyruvate: AA, lactic acid
2) OOA → PEP
• PEPCK – inhibited by insulin
3) G6P → glucose
• Glucose-6-phospatase
• Liver, kidney, NOT muscles

Glucokinase vs. Hexokinase

▪ The one that starts with G is where Glucose is STORED → LIVER!
▪ Glucokinase = glycolysis in the liver cells
▪ Hexokinase = glycolysis in the other cells
GLICOGENOLYSIS

Question types: glycogen structure, enzymes (glycogen phosphorylase), hormones

Structure:
▪ Polysaccharide of glucose, storage form
▪ Glycosydic bonds
o  1,4 (MC)
o  1,6

Most carbs in the body are stored as glycogen.

Liver glycogen = maintains blood glucose
Muscle glycogen = provide glucose during exercise
NOT stored in the BRAIN, brain depends on liver for glucose (don’t forget about KB too – during starvation).

In fasting state, would liver glycogen levels increase or decrease?

Fasting → tissues are hungry → glycogenolysis in the liver → tissues are fed (liver glycogen stores depleted)

Enzymes: glycogen phosphorylase

▪ Two forms – “A” (active) & “B”; liver and muscle form
▪ Activated by cAMP, Epi, glucagon (*exception*)
▪ MUSCLE LIVER
NOT activated by glucagon YES activated by glucagon
NOT the muscles job to elevate BGL YES liver job to regulate BGL
YES activated by Epi YES activated by Epi

Hormones
➢ Glucagone and epinephrine =  glycogenolysis
o Turns glycogen synthase off
o Turns glycogen phosphorylase on
▪ Glucagon only works on liver, NOT muscles!
➢ Thyroid hormones (T3, T4) =  glycogenolysis
➢ Insulin = glucogenesis
o Insulin – cells uptake glucose, we have  [glucose] in blood
o Turns glycogen synthase ON
➢ Glucagone = glycogen is gone
➢ Epinephrine – fight or flight
o Have to run from a bear: you need glucose, energy to sprint (hook me up with some glycogenolysis)

Glucagone:
- glycogen = gone
-  glycogenolysis
- turns glycogen synthase OFF
- turns glycogen phosphorylase ON (only in the liver, not muscle)
- secreted by pancreas ( cells)
- glucagon = found in dental emergency kits to promote glycogenolysis in hypoglycemic patients
Aldolase is plentiful in skeletal and heart muscles (4)

Pentose Phosphate Pathway: cytoplasm

Glycolysis: cytoplasm
ETC: mitochondrium (inner membrane) – in bacteria in cell membrane
Krebs cycle: mitochondrium (matrix)

Aldolytic reaction of glycolysis: FRUCTOSE BISPHOSPHATE ALDOSE (ALDOLASE) →  in heart + skeletal muscle
GLYCOGEN SYNTHESIS
➢ Synthesis and degradation – separate enzymes
➢ Glycogen synthase – major regulatory step

Glycogen synthase
➢ A dephosphorylated, active (by insulin)
➢ B phosphorylated, inactive (by Epi, glucagon)

Glycogen phosphatase (in breaking down)

• A phosphorylated, active (by Epi, glucagon)
• B dephosphorylated, inactive (by insulin)

Phosphorylation occurs at SER residues.