Protein Glycosylation & SER

Lecture 20 BSCI 420/421 Oct 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

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

N-linked glycosylation is co-translational

Formation of a GPI anchor

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

SER contains many unique enzymes and thus is the site for1. Lipid and steroid synthesis2. Detoxification of hydrophobic toxins3. Ion accumulation and release4. Glycogen breakdown

1. Lipid Synthesis

A. Phospholipids are syn. In the ER

Phospholipid synthesis

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

1B. Steroid synthesis

Cholesterol and steroid hormones are syn in the SER.

Cholesterol syn in the liver is packaged into LDL particles andshipped to other cells in the body. (uptake later)

Slide 5: Testosterone-secreting Leydig cell in the testis

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

HO-C

(soluble)

There are many different cyp450 oxidases that oxidize differenttoxins, and humans are highly variable in the genes that codefor them.

Therefore, we are highly variable in the ability to detoxify particular toxins.

I recommend that you not play Russian roulette with your abilityto 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 isInduced by the toxins or drugs, so a week later it takes more Drug to get the same effect.

3. Ion accumulation and release

Especially Ca2+, used by cells as a signal or 2nd messenger

SER & Sarcoplasmic Reticulum of muscle contain Ca2+ pumpsAnd gated Ca2+ channels (later)

4. Glycogen breakdown

Some of the enzymes for glycogen breakdown are on the SERouter surface. E.g. Glucose-6-phosphatase

Proteins and lipids are transported from ER to Golgi by vesiclesThat pinch off from transitional elements and fuse with cis Golgi

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