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Cell Components (Liquid Droplets (Function and Morphology (Lipid-storing…
Cell Components
Liquid Droplets
Biogenesis
Liquid Droplets are derived from the ER. Neutral Lipids (triglycerides and cholesterol esters) are synthesized in the ER and accumulate in specific locations between the leaflets of the ER membrane that generates a bubble
Seipin is an ER protein that facilitates the initiation of droplet formation and maintains communication in the ER
Proteins may traffic to lipid droplets via the ER or the Cytosol; the main targets are amphipathic helices and short hydrophobic hairpins
Diseases
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Lipodystrophies are diseases in which patients' adipocytes cannot make lipid droplets or are unable to maintain them.
Most congenital form is caused by the absence of seipin
They may also be caused by chronic infections; HIV cause subcutaneous peripheral lipodystrophy
Common: abnormal accumulation of lipid droplets in non-adipose tissue, commonly in the liver
Function and Morphology
Lipid-storing structures found in nearly all cells (Except RBCs). They are specialized for triglyceride storage and have large "monocular" droplets
They store cholesterol as cholesterol esters and can store hydrophobic signaling molecules such as eicosanoids and retinal esters
A set of proteins is associated with lipid droplets: including periplipins and those involved in lipid metabolism such as lipases.
Histones can also be stored on the droplet surface
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Mitochondria
Function and Morphology
Principal producers of ATP through beta-oxidation, the Kreb's cycle, and the ETC
The outer membrane is studded with channels called porins that make it permeable to small molecules (<10kDa)
The folds of the inner membrane are called Cristae which serve to increase the surface Area and bound the mitochondrial matrix
The inner membrane is nearly impermeable to ion, particularly H+, due to cardiolipin a phospholipid that four fatty acyl chains
Machinery for ATP production is on the inner membrane, and the the number of crustal is proportional to ATP production
Beta-oxidation and the Krebs cycle are mediated by enzymes contained in the mitochondrial matrix, which also contains mtDNA and ribosomes
Mitochondria are not able to oxidize very long-chain fatty acids and must first be reduced by peroxisomes
Mitochondria are necessary for the generation of Phophatidylethanolamine (PE), have essential roles in nitrogen metabolism (provide substrates for amino acid synthesis), required for synthesis of cofactors (heme), regulate entry of cells into apoptosis, catalyze the first committed step in steroid hormone synthesis
As mitochondria age, they become less efficient and RoS increase --> cell stress
Biogenesis
They are dynamic and continuously move and change length.
They regularly fuse and divide using dynamic-related proteins and the ER
Division occurs along a centrally located crista and is coordinate with DNA replication
Mitochondrial Proteins are imported from the cytosol. They are synthesized wit ha mitochondrial targeting signal (MTS).
Cytoplasmic chaperones keep these proteins in a confirmation that can be recognized by MTS receptors on the outer membrane
MTS-tagged proteins translocate from cytosol into the mit matrix thorough protein channels (proton gradient is important)
Chaperones "pull" translocating proteins into the matrix, promote cleavage of the MTS and assist folding
Mitochondrial contain their own DNA that is circular, and it encodes a few subunits of mitochondrial membrane proteins, encodes mtRNAs, and is replicated during growth
Sperm mitochondria are eliminated during fertilization and inherited maternally and mutation rate is pretty constant
Diseases
Most are caused by defects in mtRNAs, which impair mitochondrial synthesis of mGenes, which mainly encode elements of the electron transport chain -> important in neurons and muscle cells
Peroxisomes
Function and Morphology
The interior matrix has a paracrystalline core and stains strongly by EM.
The paracrystalline core of rodents is comprised of uric acid. The lack of this enzyme in human contributes to gout
They generate hydrogen peroxide from organic substances
Consumers of Molecular oxygen.
They are responsible for oxidizing a diverse set of metabolic substrate-> amino acids and lipids. (very long chain fatty acids)
They have a high level of catalase and superoxide dismutase to detoxify reactive species
Responsible for lipid interconversion; biosynthesis of ether phospholipid (plasmalogens), certain lipid signaling molecules, and bile acids
Biogenesis
They undergo fission; new peroxisomes bud from older ones. All proteins in the matrix are imported and have amino acid sequences (peroxisomal targeting signals that target them for import.
The most common signal is a C-terminal SKL sequence, recognized by Pex5
The ER is capable of de novo synthesis of peroxisomes
Diseases
Zellweger Syndrome is caused by defects in Pex proteins that compromise the ability of proteins to be imported into the peroxisome.
Empty peroxisomal membranes can be detected in liver cells of ZS patients
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Cytosol
Function and Morphology
The cytoplasm is everything within the plasma membrane that is not within the nucleus
The cytosol refers to the cytoplasm devoid of organelles and has high protein concentration as well as non-membranous particles such as ribosomes, proteasome, and aggresomes
Glycolysis: oxides glucose into 2 pyruvate molecules in a series of reactions catalyzed by enzymes resident in the cytosol. = 2 ATPs and 2 NADHs
Pyruvate produced is used by Mitochondria to produce ATP through Kreb's and ETC
Metabolites feed into the Pentose Phosphate Shunt: glucose to pentose sugars (de novo synthesis of the nucleotides) and NADPH
Site where Fatty Acid Synthesis occurs. Excess fatty acids are stored in lipid droplets as triglycerides and steryl esters, protecting cells from lipotoxicity
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Glycogen Granules
Function and Morphology
After a meal, insulin stimulates uptake of glucose into cells, especially liver hepatocytes and skeletal muscle cells.When glucose levels exceed the cell's need, glucose is stored as Glycogen (detectable easily with PAS stain)
Glycogen consists of long chains of glucose in an an alpha (1-4) glycosidic linkage together twith (1-6) crosslinks at branch points.Glycogenin resides at the center of the granule
Glycogen stored is muscle is used as fuel by fast-twitched glycolytic fibers; and in liver as a whole body supply between meals
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