Proteins' incorporation as a digestive enzyme in lysosome

[wintrymei]

I am in ninth grade Biology.

Homework Statement

I have some essay prompts given to the class by my biology teacher ahead of time before the finals. She will pick on of the prompts randomly on the day of the finals and so I must be familiar with all of them. I realize it is unscrupulous of me to try and cram information on the night before the final. I have most of this essay covered, except for one little part.

In the Golgi Apparatus, the protein is modified and sort, and then it gets packaged in a vesicle to be shipped off to its final destination throughout the cell.

So how does a protein "get inside" a lysosome?
Come to think of it, are lysosomes formed from digestive enzymes, or do the digestive enzymes enter the lysosome?
What happens when a lysosome doesn't function properly anymore?

Homework Equations

This is the whole prompt if you want to read it:
Trace the path of an amino acid during the production of a protein from the DNA in the nucleus to its incorporation as a digestive enzyme in a lysosome. Include the function of the digestive enzymes in a lysosome in your answer.

The Attempt at a Solution

This would be my essay. You can skim the stuff in italics. Even if you catch stuff that isn't detailed or explained properly, that's okay, because I'm not turning this in ... just trying to memorize its contents:
The process of the production of a protein is called The Central Dogma. This begins with the DNA in the nucleus of the cell. The first step, transcription, is making RNA from DNA. First, RNA polymerase unwinding DNA. One strand of the DNA will be used as a template from which free nucleotides assemble into a strand of messenger RNA, because RNA is single-stranded, unlike DNA. RNA has the nitrogenous uracil instead of thymine, so its base pairings are A=U, T=A, G=C, and C=G. On the mRNA molecule are many specific sequences of three nucleotides called codons.

After mRNA has been copied from the DNA's gene sequence, the mRNA carryin the instructions for assembling a protein leaves the nucleus through the nuclear membrane and into the rough endoplasmic reticulum of the cytoplasm. This ER is called the rough ER because of the ribosomes on its surface.

The next step, translation (also known as protein synthesis), involves mRNA binding to a ribosome, where the message is translated into a sequence of amino acids. Transfer RNA, or tRNA carry the amino acids that make up a protein. On one end of the tRNA molecule is its specific amino acid, and on the other end of the tRNA is a specific sequence of three nucelotides, called an anticodon. Only the information contained up to the stop codon in the mRNA molecule is used to produce the amino acid sequence. Starting with the start codon (AUG), the ribosome reads sets of three nucleotides at a time until a stop codon is reached. As the ribosome reads the nucleotides, the amino acids on the other end of the tRNA bind to each other with peptide bonds. When they bind, the tRNA is removed from the amino acid and ribosome for a new tRNA to take its place. The amino acid on that tRNA will attach the growing amino acid with peptide bonds and so on until the stop codon. Then the new protein, ribosome, and mRNA will separate.

The newly made protein is then go into the rough ER, where it may be chemically modified. Proteins that are released, or exported, from the cell are synthesized on the rough ER. Proteins produced in the rough ER move next into an organelle called the Golgi apparatus. The golgi apparatus modifies, sorts, and packages proteins from the ER. From the Golgi apparatus, proteins are then shipped to their final destinations throughout the cell or outside of the cell in a membrane package called a vesicle.

[here is where it gets awkward]

Lysosomes have many enzymes which are synthesized on the rough ER, travel to and are sorted in the Golgi apparatus. The digestive enzymes of the lysosome break down macromolecules that come in the cell and remove old nonfunctioning organelles.

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I'm not going to turn this essay in, because I copied a lot of things word for word from my textbook and the internet. I'm just going to try and memorize this information.

 

[Ygggdrasil]

So how does a protein "get inside" a lysosome?

Digestive enzymes are targeted to the lysosome by attachment of mannose-6-phosphate (M6P, a phosphorylated sugar) to N-linked glycans on the enzymes. The attachment of the sugar occurs in the Golgi. All of the digestive enzymes that are to be trafficked to the lysosome contain a specific cluster of amino acids on their exterior that tell the enzymes into Golgi apparatus to attach M6P.

The M6P receptor is a transmembrane protein that constantly shuttles between the Golgi apparatus and the endosomes/lysosomes of a cell via vesicles that bud off of these structures. In the Golgi, the M6P receptor will bind to proteins containing M6P and carry these proteins with it. In the lysosome, phosphatases remove the phosphate from the M6P group on the enzymes. Because these enzymes lack the phosphate on the mannose group, the M6P receptor no longer binds to the digestive enzymes. Thus, when the M6P receptor moves back to the Golgi apparatus, it will not carry the enzymes back with it.

Come to think of it, are lysosomes formed from digestive enzymes, or do the digestive enzymes enter the lysosome?

A little of both. Lysosomes mature from late endosomes (large membrane bound structures that contain material coming from both the Golgi apparatus [via the secretory pathway] and the plasma membrane [via endocytotic pathways]). These structures will already contain some digestive enzymes (which become activated once the lysosomes mature[see below]) and additional digestive enzymes can be delivered from the Golgi apparatus via the mechanism described above.

What happens when a lysosome doesn't function properly anymore?

By here, I assume you are asking how the cell protects itself from the digestive enzymes contained within the lysosome if, for example, the lysosome's contents are released into the cytoplasm. The answer is that the digestive enzymes of the lysosome are regulated by pH. A key step in the maturation of late endosomes to lysosomes is the acidification of the interior of the endosome by a proton pump that moves H⁺ ions into the lumen of the endosome. The acidic pH of the lysosome activates the digestive enzymes, unleashing them to chew up their targets. However, at the neutral pH of the cell, the digestive enzymes are inactive, so that the digestive enzymes will not harm the cell when they are outside of the lysosome.