1. Protein Glycosylation & SER Lecture 20 BSCI 420/421Oct 18, 2002 “I have not failed; I have only tried a hundred things that didn’t work.”-Thomas Edison 1.Glycosylation of proteins 2.SER Structure & Functions

2. 1.Glycosylation starts in the RER by addition of CHO groups during transcription.E.G. N-linked glycosylation adds a complex CHO to an asparaqine.

3. N-linked glycosylation is co-translational

4. Formation of a GPI anchor

5. Smooth ER – (lacks SRP receptors so no ribosomes bind)

6. SER contains many unique enzymes and thus is the site for 1.Lipid and steroid synthesis 2.Detoxification of hydrophobic toxins 3.Ion accumulation and release 4.Glycogen breakdown 1.Lipid Synthesis A. Phospholipids are syn. In the ER

7. Phospholipid synthesis

8. Phospholipids are transported to endomembrane system and PM by ves. transport, and to mitochondria by phospholipid exchange proteins.

9. 1B. Steroid synthesis Cholesterol and steroid hormones are syn in the SER. Cholesterol syn in the liver is packaged into LDL particles and shipped to other cells in the body. (uptake later) Slide 5: Testosterone-secreting Leydig cell in the testis

10. SER 2. Detox of hydrophobic toxins and drugs Cytochrome P-450 oxidases in SER add O or OH in a 2-step process to make toxins more soluble so they can be excreted from the body. However often the intermediate is more reactive than the original, And therefore more toxic and/or carcinogenic. E.g.: HO-C (soluble)

11. There are many different cyp450 oxidases that oxidize different toxins, and humans are highly variable in the genes that code for them. Therefore, we are highly variable in the ability to detoxify particular toxins. I recommend that you not play Russian roulette with your ability to detoxify a drug. (Len Bias & cocaine) The same applies to a new therapeutic drug. If a particular dose makes you sick, stop and call your Doctor. Also, the amount of SER and the detox enzymes in the is Induced by the toxins or drugs, so a week later it takes more Drug to get the same effect.

12. 3. Ion accumulation and release Especially Ca2+, used by cells as a signal or 2 nd messenger SER & Sarcoplasmic Reticulum of muscle contain Ca2+ pumps And gated Ca2+ channels (later) 4. Glycogen breakdown Some of the enzymes for glycogen breakdown are on the SER outer surface. E.g. Glucose-6-phosphatase

13. Proteins and lipids are transported from ER to Golgi by vesicles That pinch off from transitional elements and fuse with cis Golgi

14. Transport to the Golgi Apparatus and Retrieval of ER resident proteins.