|Lecture Notes: 5 March
© R. Paselk 2006
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Membrane Assembly/Protein Targeting
Assembly occurs on scaffolding of previous membrane
Membrane lipids are synthesized in/on membrane (Eukaryotes synthesis on cytosolic face of ER, transport by budding and Phospholipid exchange protein. Signal hypothesis for targeting of many membrane and exported proteins:
- Membrane proteins and export proteins synthesized on rER (Figure 22.29) [overhead V&V 11-40]. SRP= signal recognition protein; signal sequence= 13-36 residues with 7-13 residue hydrophobic core flanked by hydrophilic and basic residues near N-terminii; Transmembrane proteins contain an approx. 20 hydrophobic residue "stop transfer" or "membrane anchor" sequence which stays in membrane, other proteins continue through. Note that this model indicates that the amino terminus would always be extra-cytosolic in membrane proteins (this is not always the case, thus other mechanisms must be operating).
- Mitochondria illustrates more complex situations: Cytosolically synthesized precursor proteins have signal sequence. Hsp 70 helps to unfold precursor protein (ATP required), which can then pass through both membranes of mito. Inside Hsp 70 maintains in partially folded state (ATP required). It is then aided in folding by Hsp 60 ("barrel" chaperon) (ATP required). Finally it is released (ATP required), and the N-terminus is removed to give the mature protein in the matrix.
Proteins are transported in coated vesicles: membranous sacs encased in polyhedral frameworks of clathrin. (Figure 22.29) [overhead 11-42, 21-17, V&V
Introduction to Vitamins and Cofactors
- Cofactor: a co-catalyst required for enzyme activity.
- coenzyme - a dissociable cofactor.
- prosthetic group - non-dissociable cofactor.
- metal ion - a metal cofactor.
- Vitamin: a required micro-nutrient (organism cannot synthesize adequate quantities for normal health - may vary during life-cycle).
- water soluble - not stored, generally no problem with overdose.
- lipid soluble - stored, often toxic with overdose.
Let's start with a brief overview of the names, structures and physiological functions of the common vitamins as shown on the overhead: Niacin, Riboflavin [B2], Thiamine, Pantothenic acid, Biotin, Pyridoxal [B6], Folic acid, Lipoic acid, Cobalamin [B12], L-Ascorbic acid [C], and the lipid soluble vitamins A, D, E, and K). Fun facts:
- Niacin deficiency gives rise to pellagra (swollen tongue, dermatitis, neurologic and gastro-intestinal disturbances).
- Thiamine deficiency gives rise to berberi (extensive damage to nervous and circulatory systems, muscle wasting and edema - once common in Asia due to the comsumption of polished rice, which is low in nutrients, as a staple.).
- Folate and Cobalamin deficiency both give rise to megaloblastic anemia, however cobalamin deficiency also results in irreversible CNS damage.
Last modified 5 March 2007