(a) mTORC1 is specifically activated by arginine. Describe the synthesis of arginine including pre- cursors, key intermediates and other metabolic pathways we have learned about.

Human Anatomy & Physiology (11th Edition)
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Chapter1: The Human Body: An Orientation
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4.
Cells sense internal amino acid levels to couple their metabolic state with their gene expres-
sion programs. One key regulatory switch that amino acid levels control is expression of the genes
required for ribosome biogenesis – all the proteins and RNA molecules that required to generate the
small and large ribosomal subunits. Ribosome biogenesis is one of the most resource-intensive pro-
cesses in proliferating cells. In order to couple ri-
bosome biogenesis – which entails high level syn-
thesis of hundreds of proteins – with the availabil-
ity of amino acid precursors required to make
those proteins, cells evolved a signaling network
that converges on a key protein complex in the
cell known as MTOR complex 1 (MTORC1). The
net result of the signaling network shown in the
diagram is that mTORC1 is ultimately activated
by the presence of leucine and arginine in the cell
(the blunt arrows represent inhibitory interactions;
the details are not important here). When
MTORC1 is active, cells induce the gene expres-
sion program required for ribosome biogenesis.
arginine
leucine
CASTORI
Sestrin2
GATOR2
GATOR1
TSC
complex
KICSTOR
RagA
Ragu-
MTORC1
V-ATPase lator
RagC
Rheb
SLC38A9
(a) MTORC1 is specifically activated by arginine.
Describe the synthesis of arginine including pre-
cursors, key intermediates and other metabolic
pathways we have learned about.
lysosome
amino
arginine
acids
Wolfson and Sabatini, 2017, Cell Metabolism
Transcribed Image Text:4. Cells sense internal amino acid levels to couple their metabolic state with their gene expres- sion programs. One key regulatory switch that amino acid levels control is expression of the genes required for ribosome biogenesis – all the proteins and RNA molecules that required to generate the small and large ribosomal subunits. Ribosome biogenesis is one of the most resource-intensive pro- cesses in proliferating cells. In order to couple ri- bosome biogenesis – which entails high level syn- thesis of hundreds of proteins – with the availabil- ity of amino acid precursors required to make those proteins, cells evolved a signaling network that converges on a key protein complex in the cell known as MTOR complex 1 (MTORC1). The net result of the signaling network shown in the diagram is that mTORC1 is ultimately activated by the presence of leucine and arginine in the cell (the blunt arrows represent inhibitory interactions; the details are not important here). When MTORC1 is active, cells induce the gene expres- sion program required for ribosome biogenesis. arginine leucine CASTORI Sestrin2 GATOR2 GATOR1 TSC complex KICSTOR RagA Ragu- MTORC1 V-ATPase lator RagC Rheb SLC38A9 (a) MTORC1 is specifically activated by arginine. Describe the synthesis of arginine including pre- cursors, key intermediates and other metabolic pathways we have learned about. lysosome amino arginine acids Wolfson and Sabatini, 2017, Cell Metabolism
(b) In addition to arginine, mTORC1 also senses leucine. Monitoring leucine and arginine levels pro-
vides mTORC1 with key information about different classes of amino acids as well as two other key
metabolic processes in addition to amino acid synthesis. What are the two classes of amino acids, and
why might it be advantageous for mTORC1 to receive information about both of these classes? What
are the other two processes and how does mTORC1 indirectly sense them?
(c) Given its role in regulating ribosome biogenesis, propose a speculative argument for why it might
be useful for mTORC1 to specifically sense arginine rather than other amino acids.
Transcribed Image Text:(b) In addition to arginine, mTORC1 also senses leucine. Monitoring leucine and arginine levels pro- vides mTORC1 with key information about different classes of amino acids as well as two other key metabolic processes in addition to amino acid synthesis. What are the two classes of amino acids, and why might it be advantageous for mTORC1 to receive information about both of these classes? What are the other two processes and how does mTORC1 indirectly sense them? (c) Given its role in regulating ribosome biogenesis, propose a speculative argument for why it might be useful for mTORC1 to specifically sense arginine rather than other amino acids.
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