• Two linked AA chains by disulfide bonds
• Produced by Beta cells of the pancreas
• Decreases Bool Sugar

• Produced by Alpha cells of pancreas
• Increases Blood sugar

Insulin Receptor (A)

Basic structure

• Precuresor is a protien with a signal peptide that is cut off, protein is then cut into two parts, an alpha and a beta portion. Assembles into an alpha₂beta₂ dimer with 3 disulfide bonds
• Beta portions are the transmembrane portion, contiains 3 key Tyr resisdues.
• Alpha portions bind insulin.

Insulin Receptor (B)

Reaction to insulin binding

• The first insulin molecule binds to the first alpha portion which causes phosoralization of the 3 tyr portions of the Beta subunit. The second insulin binds causes the other try for the other beta unit to phosporalate.
• The phosphoralation of the tyr residues causes tyr kinase activity. Which phosphorylates IRS-1, (insulin receptor substrate I)
• IRS-1 -> Phosphoinositide-3-kinase -> PIP3 & others -> -> -> cAMP phosphodiesterase & Phosphoprotein phoshatate I
  

Glucose Transporters

GLUT 1-7, 12

General overview

• GLUT 1: Located in erythrocytes, kedney, colon, blood/brain barrier
• GLUT 2: Liver, beta-cells of pancreas - low affinity for glucose, but high capacity
• GLUT 3: Barin & neurons - high affinity for glucose
• GLUT 4: muscles and adipocytes - the ONLY insulin senstive transporter
• GLUT 5: Small intestine; fructose transporter, not glucose
• GLUT 6: considered a psuedo gene
• GLUT 7: Liver microsomes - connected with G6P and glucose export from the liver.
• GLUT 12: unk function
  

Glut 4

(Response to Insulin)

• Found in muscle and fat cells
• When the insulin signal is transmitted vesicals containing this will fuse adding this to the cell surface.

GLUT 2

(More specific)

• Found in liver and Beta cells of the pancreas
• Special property is that it keeps the glucose levels inside these cells propotional to blood glucose levels.
  

elevates cAMP

decreasing glycolysis

increasing F(2,6)Bisphoshatase

decreases F(2,6)BP

increases gluconeogenesis

increcreases glyconeogenesis

increases TAG breakdown

increases ketone bodies

decreases blood pH

• Two Types
• 1-0.5% US pop, insufficient production of insulin
• 2  - Over 7% of US pop, bad or not enough receptors

Isopernoid

(Are?)

• Strutural components of membranes
• Endocrine hormones, bile acids
• vitamins A and D
  
• part of vitaments E&K, chlorophyll, heme C, some neculeotides, perenylCys residues on proteins
• terpenes
  

Structureal component of membranes

Energy Storage

Paracrine hormones (eicosanoids)

• Has many biochemical functions, the one of interest for this lecture series is 2 AcCoA come together to from acetoacetyl-CoA (thiolase) then another adds on to form HMG-CoA (HMG-CoA synthase)
• Costs 1 ATP to remove it from a mitocondria.

• Convers Mevalonate to Phospomevalonate using 1 ATP.
• Found in peroxisomes.

• Conversts phospomevalonate to mevalonate diphosphate using 1 ATP
• Found in peroxisosmes

• Converts Mevalonate diphosphate to IPP, CO2, isopentenyl diphosphate using one ATP->ADP
• Found in peroxisomes

Mevalonate diphosphate

(pyrophosphate)

• Converts HMG-CoA to Melavonate in two steps utilizing 2NADPH
  
• Contains 7 transmembraine domains
• First commited step in isoprenoid synthesis
• Lives in the walls of the ER
• Activity decreased by phosphorylation.
  
• Activity decreased by cholesterol and a non-sterol derivate of mevalonate, farnesol.
  

• Conversts IPP inot dimethylallyl diphosphate DMAPP
• Found in peroxisomes

Prenyl Transferase

(FPP synthase)

• Condesation reaction of DMAPP and 2 IPP to make farnesyl PP (FPP).

Farensyl PP

FPP

• Made in mito
• made using an alternative prenyl transferase
• hook FPPs in trans double bonds together( 8-10, 40-50C)
• Final step is the additon of p-OH-benzoic acid.

• Ancored in the ER membrane.
• As diphospate esters they carry the sugars that are destined to be used as glycoprotein
• synthized by cis polyprenyl diphospatesynthase, which elongates FPP.
• The end is not cis nor trans, then two trans then all cis double bonds.
• Largest non saponifiable lipids

• Formed usually by cys, aliphatic amino acids x2, anything.
• Big example gama G proteins.

• We use about 20g a day, 500 mg/day are lost in feces
• Created from cholesterol in a multistep process involving a number of cytochrome P450-mediated oxygenases.
• iso-octyl side chain is removed as C3 leaving 5C acidic side chain. The double bond is lost and the A&B rings fuse.

• LDL is the most common way for cholesterol to travel in the blood. It consists of a protein called B-100 and is surrounded by phospholipids.
• LDL receptor cause cells to take in the LDL bubble

Caused by a lack of LDL recptorns

Have really really high cholesterol levels.

terpenes

sesquiterpenes

juvenile hormone

caretanoids

• ingest on average 100 g a day
• 400 g used for metabolism, 10-15% of our dayly enegry supply
• All proteins is absorbed, not excreted, and what is not used to build muscle is turned over into energy
• Esential Amino Acids - His, Lys, (2/3 basic aa) Ile, Leu, Val,(branch chain) Phe, Try (aromatic)
• Rest considered Non-essential