307 - mTORC (Patricia Roque Lecture)
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what is metabolism?
- Anabolism + Catabolism
- Term used to describe all chemical reactions involved in maintaining the living state of the cells and the organisms
what is rapamycin?
- Inhibits mTORC1
- Antibiotic - Antifungal (anticandial)
- Derived from Streptomyces hygroscopicus (bacterium)
- Modifications to C40 hydroxyl group
what does mTORC regulates?
- Cellular metabolism
- Nucleotide synthesis
- Protein synthesis
- Lipid synthesis
what are the roads that lead to mTORC1 upstream?
- Insulin = ↑ mTORC
AA = ↑ mTORC
how is mTORC inhibited?
- ↑ AMP to ATP ratio
- = ↓ energy status will inhibit mTORC (you don't want metabolic/cell growth division pathways going on when you have ↓ energy)
how does mTORC control metabolism "downstream"?
what is stunting?
- Chronic energy malnutrition
- Non appropriate height for age
- Deficiency in essential AA like Tryptophan and Lysine
what is wasting?
- Acute process
- Very thin
- Height appropriate for age
what is childhood stunting traditionally attributed to?
- Micronutrient deficiencies
- Poor hygiene
- Lack of breast feeding
- infectious diseases
what was noticed in stunted children in Malawi?
- Lower serum concentration of AA's
- Diet: primarily from maize
what are the AA theatre limiting in corn?
- Tryptophan: inv. in making Niacin (B3)
what are some growth processes regulated by mTORC1?
- Chrondral plate: where bones grow
- Skeletal muscle
- Small intestine homeostasis
- Immune function
- Organ size
what are some diseases associated with lack of Niacin/Tryptophan?
- Dermatitis: in the collar bones and the hands
what does mTORC have to do with stunting?
- mTORC senses ↓ AA
- Deficiency in AA inhibits mTORC
- Results in stunting and wasting
what are the implications of mTORC1 inhibition?***(ADD FORM NEW SLIDES**)
- Organ transplant
- If there is inhibition of mTORC, you don't make interleukin 1
- Cancer therapy
- Proto oncogenes and tumor suppressor genes linked to mTOR pathway
- (stops protein synthesis growth***)
how do drug eluting cardiac stents and mTORC1 inhibition related?(**8 add form new slides)
- A stent is put in an artery if 70% is blocked
- They coat the stent with an mTORC1 inhibitor to inhibit cellular growth
how are ageing and mTORC1 inhibition related?
They're tested on pets to see if they work as an anti ageing drug
what is the meaning of life?
- Survival and reproduction
- Cellular level: maintain function and/or replace itself
what extra and intra cellular signals does mTOR investigate?
- Nutrients and Growth factors (ex. insulin)
- *Nutriens are involved in all aspects of cellular function
what does mTOR regulate?
- Cellular metabolism
- The balance between intracellular anabolism and catabolism
- Proliferation: A cell needs to grow before it divides
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