Our cells engage in protein production, and many of those proteins are enzymes responsible for the chemistry of life.
— Randy Schekman

I. Cell metabolism

  1. Structure Biology of the Citric Acid Cycle: The citric acid cycle is at the center of cellular metabolism. It plays a starring role in both the process of energy production and biosynthesis. [PDF]

  2. Regulation of Cholesterol Synthesis:

    • Discovery of receptor-mediated endocytosis (RME) of LDL: Michael S. Brown and Joseph L. Goldstein.

    • Part 1: Feedback Regulation of HMG CoA Reductase [iBiology Talk video]

    • Part 2: Schnyder Corneal Dystrophy: Importance of UBIAD1 in Regulation of Cholesterol [iBiology Talk video]

    • Goldstein, Joseph L., and Michael S. Brown. “A Century of Cholesterol and Coronaries: From Plaques to Genes and Statins.” Cell 161, no. 1 (2015): 161–72. [PDF | PMID: 25815993 | DOI Link]

    • Question at 1970s:

      1. Receptors on the plasma membrane communicate with proteins in the nucleus, endoplasmic reticulum, lysosomes, mitochondria, and other structures, how is this cell-wide communication articulated ?
      2. How does a cell regulate a metabolic pathway whose active components reside in different subcellular compartments ?

  3. Regulation of Energy metabolism

  4. Lysosome role in metabolic signalling

    • Discovery of Lysosome: [Christian de Duve, 1959]
    • Review in 2019: The lysosome as a cellular centre for signalling, metabolism and quality control (Rosalie and Roberto, 2019) [PDF | PMID: 30602725 | DOI Link]
    • mTORC1 activation of Lysosomal membrane:

  5. Nutrient sensing machinery

    • Cholesterol:
      — LYsosomal CHOlesterol Signaling protein (LYCHOS, previously annotated as G-protein coupled receptor 155), Reported at 25-Aug-2022 [PDF | PMID:36007018 | DOI Link]
      — PATCHED,
      — HMG-CoA reductase,
      — Niemann-Pick type C protein 1 (NPC1), Reported at 11-Jul-1997 [PDF | PMID:9211849 | DOI Link]
      — SREBP(Sterol regulatory element-binding protein),
      — SREBP cleavage-activating protein (SCAP),

    • Amino acids:
      Review: The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway (Wolfson and Sabatini, 2017) [PDF | PMID:28768171 | DOI Link]
      — Leucine > Sestrin2
      — Arginine(Cytosolic) > CASTOR1 [(David M Sabatini’s lab, 24/03/2016) | PMID: 26972053]
      — Arginine(Cytosolic) > RBM39 [(Michael N Hall’s lab, 09/11/2023) | PMID: 37804830]
      — Arginine(lysosomal) > SLC38A9
      — S-adenosylmethionine > SAMTOR
      — S-adenosylmethionine > Unmet(Fly specific)
      GATOR2 > Nutrient sensing hub! [CryoEM Structure of human GATOR2 complex | Valenstein et al., 2025]

    • Glucose:
      — AMPK

    • Nitrogen sensing in yeast cells

  6. Open questions

    • How cells sense, integrate and respond to nutrient availability and how lysosomes are involved in the process?
    • How amino acids were sensed? More amino acid sensors ?
    • How different or similar the amino acid and nutrient inputs are that drive mTORC1/TORC1 signaling in diverse organisms ?
    • Is GATOR2 the nutrient sensing hub complex ? How does it work to integrate multiple nutrient inputs ?
    • How does brain sense the stress of energy supply and initiate its response program?
    • what is the nitrogen sensor in yeast cells ?

II. Cell signaling in innate immune response

  • Pattern recognition receptors (PRRs): These receptors are crucial for sensing danger signals.
    • Toll-like receptors (TLRs): TLR4 []
    • NOD-like receptors (NLRs)
    • RIG-I-like receptors (RLRs)
    • Key question at that time: What is the intracellular receptor of LPS ?
    • Cytosolic DNA sensor: cGAS [James Chen Lab, 2012]
  • Pathogen-associated molecular patterns (PAMPs)
  • damage-associated molecular patterns (DAMPs)

1. Discovery of cytosolic DNA sensor

  • Key question at that time: What is the cytosolic DNA sensor that trigger antiviral response ?
  • pioneering works:
    1. Stetson, Daniel B., and Ruslan Medzhitov. “Recognition of cytosolic DNA activates an IRF3-dependent innate immune response.” Immunity 24.1 (2006): 93-103. [PMID: 16413926]
    2. Ishii, Ken J., et al. “A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA.” Nature immunology 7.1 (2006): 40-48. [PMID: 16286919]
  • Key discovery works:

III. Immune surveillance against cancer

IV. Cell death pathways

  1. Programmed cell death-Apoptosis
  • Discovery of the genes:
  • Identification of Apaf1
  1. Inflammation induced pyroptosis
  • Discovery of GSDMD

Textbooks

  1. Fundamentals of Biochemistry, Life at the Molecular Level, 5th edition [View PDF] textbookbioche001
  1. Lehninger Principles of Biochemistry, 4th edition [View PDF] textbookbioche002
  1. Molecular Biology of The Cell, 6th edition [View PDF] textbookbioche003

Online Courses

  1. BIOLOGICAL CHEMISTRY I, MIT OpenCourseWare [Source]

  2. BIOLOGICAL CHEMISTRY II, MIT OpenCourseWare [Source]

  3. BIOCHEMISTRY LABORATORY, MIT OpenCourseWare [Source]

    • Instructor: Dr. Elizabeth Vogel Taylor
    • LABORATORY MANUAL: Student manual on the laboratory activities of the course. [PDF]
    • EQUIPMENT AND SUPPLIES: A list of equipment and supplies used for the biochemistry laboratory activities of the course. [PDF]

  4. Principles of Biochemistry, HarvardX, EdX:
    This introduction to biochemistry explores the molecules of life, starting at simple building blocks and culminating in complex metabolism. [Source]

    • Instructors: Alain Viel, Rachelle Gaudet

  5. LIPID MAPS

  • Edward A. Dennis (2010) “LIPID MAPS Lipid Metabolomics Tutorial”:
    These tutorial videos were prepared for students in the UCSD School of Medicine and School of Pharmacy and Pharmaceutical Sciences by Professor Edward A. Dennis, Department of Chemistry and Biochemistry and Department of Pharmacology, School of Medicine, University of California, San Diego. [Tutorial outline PDF]
  1. LIPID MAPS Spring School, April 2021

Ref. Database

Nobel laureates

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  • George E. Palade, Yale University, School of Medicine, New Haven, CT, USA Nobel Prize in Physiology or Medicine 1974
    Intracellular Aspects of the Process of Protein Secretion [Read the Lecture | Source]

  • Christian de Duve, Rockefeller University, New York, NY, USA; Université Catholique de Louvain, Louvain, Belgium Nobel Prize in Physiology or Medicine 1974
    Exploring Cells with a Centrifuge [Read the Lecture | Source]

  • Hans Krebs, Sheffield University, Sheffield, United Kingdom Nobel Prize in Physiology or Medicine 1953
    The Citric Acid Cycle [Read the Lecture | Source]

  • Fritz Lipmann, Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USA Nobel Prize in Physiology or Medicine 1953
    Development of the Acetylation Problem: A Personal Account [Read the Lecture | Source]