-sucrose

-lactose 

-high fructose corn syrup (more recent form) 

-disaccharide 

-made of fructose and glucose 

-not absorbed in the gut; must be cleaved into monosaccharides before absorption 

-enzyme (sucrase) cleaves sucrose in brush border of intestine 

-milk sugar 

-disaccharide 

-made of galactose and glucose 

-must be hydrolyzed into individual sugar components for absorption

-lactase breaks down lactose 

- Become lactose intolerant 

-without lactase you are unable to break down lactose

- lactose will move through the intestines without absorption, collecting water along the way which causes diarrhea and cramping 

- Man made sugar product 

-Large scale cleavage of sucrose; collect purified fructose 

-fructose is much sweeter than sucrose 

-G6P

-Pyruvate 

-Acetyl CoA

-nucleotide synthesis

-RNA/DNA biosythesis 

-Fatty acid and cholesterol synthesis

-Protein catabolism

-Speciality molecule synthesis (hormones, porphyrin)

-Galactose 

-Glucose

-Fructose

-Mannose 

-Five carbon sugar 

-Proven to help prevent caries 

-Inhibits growth of Streptoccocus mutans and decreases ability of S. mutans to stick to teeth and biofilm

- It decreases the number of s. mutans bacteria in the oral cavity 

-Decreases ability of bacteria to stick to teeth and biofilm 

Part 1: 10 days of pulses of different sugars of glucose, glucose/sorbitol, glucose/xylitol -> measured the number of CFUs; showed xylitol reduced CFUs 

Part 2: Comparison of the number of caries children had whos mother consumed xylitol containing products during pregnancy and infancy versus those mothers that did not use xylitol.

-> xylitol using mothers children had a 71% lower caries occurance 

->babies develop oral biofilm from mothers

- Tissue Specificity 

-Enzyme concentration

-Compartmentalization

-Protein Modification

-Allosteric control

Cells and tissue have a specific activity based off of genetics. Either a cell/tissue/organ has a function or it doesn't. 

-Big regulator of activity 

-Gives specificity to metabolism

Examples: 

-Glucose-6-phosphatase 

-Liver pyruvate kinase 

-Example of tissue specificity 

-Enzyme that breaks down G6P to glucose

-Only expressed in hepatocytes of the liver 

-Differentiates hepatocytes from all other cells because of the expression of this enzyme 

-Example of tissue specificity 

-Involved with glycolysis

-In all cells, but in the liver this enzyme is highly regulated 

Enzyme concentration 

-How much of a particular protein or total abundance of that protein within a cell 

-Different from tissue specificity because enzymes are regulated up or down; change activity of cell by changing the concentration of proteins

-Done at transcription and translationally level

Examples: 

Phosphoenolpyruvate carboxykinase (PEPCK) 

-Example of enzyme concentration

-Enzyme that contributes to glucose biosynthesis 

-Regulated at the DNA level (genes highly regulated)

-Many membrane enclosed compartments in cells 

-More than 90% of metabolites are hydrophilic or charged. This means that they will not diffuse across the lipid bilayers.

-Even small molecules like H2O, urea, ammonia will not diffuse 

-Use proteins to transport molecules which can be regulated 

Examples: 

-Fatty acid bio synthesis takes place in cytoplasm

-Oxidation occurs in the mitochondria. Membrane transportation can determine if you have synthesis or degredation of fats 

-Proteins are chemically modified after synthesis

-"Covalent chemistry" 

Examples:

Phosphorylation

ADP-ribosylation

-Example of protein modification

-Most common form of protein modification

-Occurs at 1 of 3 AA residues that have a hydroxyl side chain residue (serine, threonine, tyrosine). 

-Requires ATP to do 

-Protein kinases catalyse phosphorylation

-Phosphotases remove the P and change back to -OH

-Example of Protein modification

-Adds ADP-ribose to proteins 

-Common action of bacterial toxin -> ADP ribosylation of important enzymes in humans which cause the disease (cholera/pertussis)

-Enzyme has allosteric site that can bind molecules quickly causing catalytic site change. 

-Initiates very quickly and duration of signal can be very quick

-If concentration of the metabolite drops then it removes itself from allosteric site.

-"Fine tuner" of metabolism

-Allows for minimization of fluctuations in the body

Red muscle: High amount of mitochondria which have a lot of iron containing enzymes (gives red color)

-burns glucose through oxidative phosphrylation and electron transport chain (makes a lot of ATP per glucose)

-uses glucose preferentially  

-Example: heart 

White muscle: "flight or fight" muscles

-not as much mitochondria

-uses TCA cycle and glycolysis

-Can generate glucose in anaerobic conditions 

-Major glucose user 

-Can burn other fuels if needed (ketone bodies)

-

-Exclusive user of glucose 

-No mitochondria so can't run citric acid cycle/no oxidative phosphorylation

-Depends on glycolysis to burn glucose 

-Can't oxidize NADH fast enough so it has a high level compared to other cells -> this drives the product of glycolysis to lactate (instead of pyruvate) 

-Main glucose user 

-At rest the brain and kidney use the most glucose 

-Resorbs molecules that the body needs -> depends on transport mechanisms that require glucose 

-Kidney cortex cells can synthesis a small amount of glucose but not enough to sustain life 

-"Unselfish organ"  -> maintains blood glucose levels 

-Synthesis glucose by gluconeogenesis (hydrolyzes G6P to free glucose)

-Stores glucose as glycogen

-Both muscle and hepatocytes store glycogen but only liver calls have G6Phosphatase to convert glycogen back to free glucose (muscle can't do this and only uses it for itself 

-Uses fatty acids for fuel NOT glucose 

Has transporters on brush border of intestine that transport in nutrients 

-Transports glucose into body primarily unaltered 

-Burns the amino acid glutamine (20x the concentration of all other AAs in the blood)

-Also uses ketone bodies for fuel (biproduct of fatty acid synthesis)

Insulin and Glucagon 

4.5 mM

(100mg/100mL)

-Insulin is released from Beta cells in pancreas

-Glycogen storage (synthesis) will increase in liver and muscle

-Glycogen breakdown will decrease 

-Glycolysis will increase

-Lipid synthesis increases

-Gluconeogenesis will decrease 

-Alpha cells of pancrease release glucagon

-Glycogen breakdown increases

-Glycogen synthesis decreases

-Glycolysis decreases

-Gluconeogenesis increases 

Antagonistic 

-Glucose and lipid synthesis are dictated by the relationship between these two hormones

Glucagon

Epinephrine

ACTH

Serotonin

Two opposing G-protein complexes 

(Gsa and Gia) 

-PGE

-Adenosine 

-Has three subunits-> alpha, beta, gamma (assume beta and gamma are same unit)

-Galpha can be stimulatory or inhibitory ->Gsa is stimulatory and Gia is inhibitory 

1. Hormone binds to receptor which causes a conformational change 

2. Hormone receptor complex has high affinity for G-protein complex and binds to the Ga unit (can be S or I)

3.Binding of hormone causes a conformational change in the Ga -> the GDP attached to the unit is replaced by GTP and the subunit detaches from gamma/beta

4. Ga now has a high affinity for adenylyl cyclase and binds to it 
*Can inhibit or stimulate adenylyl cyclase at this point*

5. Hormone dissociates from the hormone receptor. Ga has a GTPase associated with it that cleaves GTP by itself at a rate. Once GTP is cleaved to GDP Ga no longer has affinity for adenylyl cyclase .

6. Ga then rejoins with beta and gamma subunits and is inactivated.

7. If hormone is still off balance the process will repeat itself.  

aka Whooping Cough

-Produces a protein toxin that causes ADP-ribosylation of the Gia complex in lung alveoli

Substrate: NAD 
Product: Nicotinamide
(what causes the ADP ribosylation)  

-Blocks the GDP/GTP exchange meaning:

*Never get to active Gia

*Gsa will take over and cause adenylyl cyclase activity to skyrocket (since there is no opposing Gia action).

*cAMP production does not end -> causes cells to lose H2O and Na+ which accumulates in the interstitial space of lung cells

-Lungs fill with fluid and can't breathe 

-Cholera toxin is an ADP-ribosylase that attacks the intestinal epithelium

-Same activity as Pertussis but different substrate

Substrate: NAD+

Product: Nicotinamide 

-ADP-ribosylation occurs on the Gsa-GTP 

-Blocks the action of GTPase -> causes Gsa to be locked in stimulatory mode 

-Never able to  turn Gs off which leads to:

*Constant activation of adenylyl cyclase 

*high levels of cAMP

*leads to H2) and Na+ loss from the intestinal epithelium

*causes massive diarrhea, dehydration and death

-cAMP is produced by activated adenylyl cyclase 

-cAMP activates protein kinase A -> phosphorylates all kinds of proteins and is integral to metabolism regulation

-cAMP is broken down to 5-AMP by cyclic nucleotide phosphodiesterase 

*5-AMP is not a signal molecule 

Caffeine

Theophylline 

*causes a body rush by increased levels of cAMP -> increased heart rate, blood pressure, alertness* 

Insulin stimulates glucose uptake and consumption

-increased glucose transport

-glucose stored in muscle as glycogen

-glucose stored in adipose as fat 

Tyroskin kinase 

-causes a cascade of phosphorylation 

- Located on plasma membrane 

-Has 2 alpha and 2 beta subunits (beta subunit transverse the membrane)

-Is a tyrosine specific phosphorylator 

Insulin cascade 

-When insulin binds to insulin receptor the receptor undergoes autophosphorylation at a tyrosine. 

-Once it is phosphrylated it is able to phosphorylate other proteins 

-First one it activates is IRS-1 which has a tyrosine phosphorylated by the insulin receptor producing ADP.

-IRS-1 then goes off to phorphorylate other proteins 

The first insulin receptor found

-Is a tyrosine kinase 

-once phosphorylated by the insulin receptor it goes off to activate/inactivate other proteins via phosphrylation