Smile Formulas
Some pathways
- Urea cycle,
- nucleotide, DNA, RNA, protein,
- amino acid synthesis
- Dont depend on fed/fasting state,
- so formulas do not apply.
Phosphorylation and Dephosphorylation
- Fed → Insulin → Dephosphorylation
- Mnemonic: Insulin Hate HSL
- so prick with PIN (PGE, Niacin, Insulin)
ㅤ | Fed state | Fasting state |
Hormone | • Insulin (anabolic hormone) | • Glucagon • Hypoglycemia in CAMPil • give Glucagon injection |
↳ MOA | • Activates phosphodiesterase • ↓ cAMP | • Activates adenyl cyclase → ATP • ↑ cAMP → activates protein kinase A ↳ Glycogen phosphorylase (activated) ↳ Glycogen synthase (inhibited) |
ㅤ | ㅤ | Other Counter-regulatory hormones • Epinephrine/norepinephrine • Growth hormone • Glucocorticoids • Thyroid hormones |
State | Dephosphorylated | Phosphorylated |
Lipase activated | Lipoprotein Lipase (LPL) | Hormone Sensitive Lipase (HSL) Inhibited by • Insulin • PGE1 • Niacin • Insulin hate HSL • so prick with PIN (PGE, Niacin, Insulin) |
↳ Function | • Chylomicron TGA → FA + Glycerol • to enter Adipose cells in fed state | • Adipose TGA → FA + Glycerol • for transport to liver in fasting state |
ㅤ | Enzymes & Pathways activated | Enzymes & Pathways activated |
Pathways activated | • Glycolysis + • Link Reaction + All anabolic pathways • Glycogen synthesis • Cholesterol synthesis • FA synthesis • Protein synthesis | • Gluconeogenesis + All Catabolic pathways • Glycogenolysis • KB synthesis / breakdown • FA (β) oxidation • Peripheral lipolysis • Amino acid oxidation |
Enzymes activated | All anabolic + • Glycogen synthase • Acetyl CoA carboxylase • HMG CoA reductase Glycolysis enzymes • Phosphofructokinase • Pyruvate DH Exception ATP Citrate Lyase ↳ FA synthesis ↳ Citrate → Acetyl CoA ↳ activated by insulin ↳ Active in phosphorylated state | All catabolic + Gluconeogenesis enzymes • Fructose 1 , 6 bisphosphate • Glycogen phosphorylase NOTE: • Gluconeogenesis is anabolic • Glycolysis is catabolic |
Compartmentalisation | Cytoplasm | Mitochondria |
ㅤ | All above pathways + • Glycogenolysis • HMP shunt | All above except Glycogenolysis + • TCA • ETC • PDH |
Others | Cholesterol synthesis (Steroids) ↳ Cytoplasm + SER Bile acid synthesis (Steroids) ↳ Smooth Endoplasmic Reticulum | Oxidised in Peroxisomes ↳ Very long chain fatty acid + ↳ Branched chain Fatty acids |
Both | ㅤ | ㅤ |
ㅤ | • Start in mitochondria • Finish in cytoplasm | PUBG • Pyrimidine Synthesis • Urea cycle • Haem synthesis (blood) • Gluconeogenesis ↳ Oxaloacetate reaches Cyp for gluconeogenesis |
Example Questions and Applications
- Which does not occur in mitochondria? (AIIMS Nov 2016)
- Ans: Fatty acid synthesis (anabolic, cytoplasm, Smile Formula 4).
- Which is active in dephosphorylated state? (PGI May 2017)
- Ans: Glycogen Synthase, Acetyl CoA Carboxylase, Pyruvate Dehydrogenase (anabolic or insulin-activated, Smile Formula 3).
- Insulin promotes lipogenesis by all except?
- Ans: Inhibiting Pyruvate Dehydrogenase (insulin activates it, Smile Formula 3).
- Hormone Sensitive Lipase is NOT activated by?
- Ans: Insulin (activates LPL, not HSL, Smile Formula 2).
- Which is repressed by insulin? (PGMEE 2012-13)
- Ans: Pyruvate Carboxylase (catabolic, Smile Formula 2).
Warburg Effect (Aerobic Glycolysis in cancer cells):
Miscellaneous terms | Features |
Pasteur Effect | In presence of O₂ • Normal cells suppress anaerobic glycolysis • Prefer aerobic respiration • Saves glucose |
Crabtree effect | In presence of O₂ + too much glucose • TCA cycle activity ↓↓ • Pyruvate → Lactate • Latic acidosis |
Rapaport-Leubering Shunt | Occurs only in RBCs Glucose ⇒ ↳ 90%: normal glycolysis = + 2 ATP/glucose ↳ 10%: enters RL shunt • To generate 2,3-Bisphosphoglycerate (2,3-BPG) • No ATP produced • Skips Phosphoglycerate kinase step ↳ (normally produces ATP) |
Warburg Effect | Normal Cells • Aerobic Oxidation • Use PKM1 (high activity) • Pyruvate → TCA cycle = 32 ATP Metabolic Reprogramming in Cancer Cells • Use PKM2 (low activity) • Pyruvate → Lactate = 2 ATP ↳ even with O₂ → referred as Aerobic glycolysis • High glucose demand & consumption ↳ Glucose hunger ↳ Cachexia - mediators TNF-a, interleukin-1 ß, and interleukin-6. Function • Generates metabolic intermediates ↳ pyruvate/lactate • for cell growth/division Principle for • 18-FDG (Fluorodeoxy glucose) PET scans • detects metastasis via increased glucose uptake |
Van der bergh's reaction | • Direct positive ⇒ Obstructive jaundice |
PET Scan
- IOC → for mets
- Requires a positron-emitting radioisotope
- Tc99m cannot be used → emits gamma rays
- Dedicated positron emitter used:
- F18
- Most common radioisotope
- Half-life: 110 minutes = 2 hours
- Most common ligand:
- FDG (Deoxyglucose)
FDG (Deoxyglucose) & Cancer
- Basis: Warburg effect → increased glucose uptake in cancer cells
False Results
- False negative:
- Low-grade tumors
- Low-grade typical carcinoid
- Bronchoalveolar carcinoma
- Mnemonic: Typical car () nte backil (BAC) → False negative pet ooddi
- High blood glucose
- Cancer cells take glucose instead of FDG
- Blood glucose should be normal before the test
- False positive:
- Infections → TB
- Inflammations
Physiological Uptake (Normal high uptake sites)
- Excretory system
- Urinary bladder
- Kidneys
- Urinary tract
- Bilateral supraclavicular areas (brown adipose tissue)
Principle of PET
- Annihilation coincidence circuit
- Mnemonic: Put PET in AC
- PET radionuclide emits a positron (β⁺)
- Positron travels a short distance in tissue
- Positron meets an electron from normal body tissue
- Positron + electron → annihilation
- Entire rest mass converts to energy
- Rest mass energy of one electron or positron = 511 keV
- Energy is released as two gamma photons
- Each photon has 511 keV
- Total energy released = 2 × 511 keV = 1022 keV
- Photons move in opposite directions (180°)
- PET detects both photons at same time
- Dual photon peak at 180°
- When FDG is given:
- F18 emits a positron.
- The positron reacts with an electron in the body and they annihilate each other.
- They coincide on the detector.
- If they coincide at the same time, they are detected.
- This is called a coincidence circuit.
PET-CT
- Fusion / hybrid imaging
- Used for:
- Cancer staging
- Assessing treatment response
- Detecting recurrence
Physiological Significance of 2,3-BPG / 2,3 DPG
- Maintains taut state of haemoglobin.
- Binds to β-chains of globin of HbA → facilitates O₂ release at tissues.
- Shifts the ODC to the right.
- HbF has α and γ chains
- unaffected
- favor O₂ absorption from maternal blood.
- Factors increasing
- Anemia, hypoxia, high altitude,
- exercise, hyperthyroidism, ↑↑ growth hormone/androgen,
- Inosine, pyruvate, phosphate.
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