Anabolic Steroids: What They Are, Uses, Side Effects & Risks


A Beginner’s Guide to the Body and Health



Intended for people who want a clear, easy‑to‑understand overview of how our bodies work, why we stay healthy, and what you can do day‑to‑day to keep it that way.



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1. The "Big Picture" – How the Body Works



System Main Parts What It Does


Circulatory Heart, blood vessels, blood Pumps oxygen & nutrients everywhere; removes waste


Respiratory Lungs, trachea, diaphragm Brings in oxygen, expels carbon dioxide


Digestive Mouth → stomach → intestines → liver/ducts Breaks food into usable molecules


Nervous Brain, spinal cord, nerves Controls thoughts, actions, sensations; sends signals


Musculoskeletal Bones, muscles, joints Supports body, allows movement


Endocrine Glands (pituitary, thyroid, etc.) Releases hormones to regulate processes


Immune White cells, lymph nodes, antibodies Detects and fights pathogens


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3. Detailed Pathways



3.1 Energy Production: Aerobic Respiration & the Citric Acid Cycle




Glycolysis (Cytosol)


- Glucose → 2 Pyruvate + 2 ATP + 2 NADH


Pyruvate Oxidation (Mitochondrial Matrix)


- Pyruvate → Acetyl‑CoA + CO₂ + NADH


Citric Acid Cycle (TCA, Kreb’s Cycle)


- Acetyl‑CoA + Oxaloacetate → Citrate → … → Oxaloacetate

- Produces 3 NADH, 1 FADH₂, 1 GTP per acetyl‑coA




Oxidative Phosphorylation (Electron Transport Chain)


- NADH/FADH₂ → Complex I/III → ATP synthase (ATP ≈ 2.5 mol/mol NADH, 1.5 mol/mol FADH₂)

Key Metabolites & Fluxes





Pyruvate: Branch point to lactate (via LDH) or acetyl‑CoA (via PDH).


Lactate: Exported by MCT1/4; reimported for gluconeogenesis.


Acetyl‑CoA: Feeds TCA cycle, lipid synthesis.


α‑Ketoglutarate, Succinyl‑CoA, Oxaloacetate: Intermediate metabolites in TCA and anaplerotic pathways.







2. How the Liver’s Gluconeogenic Pathway Shapes Glucose Homeostasis




Basal Glycogenolysis (Glucose‑6‑Phosphatase)


- The liver’s glucose‑6‑phosphatase catalyzes dephosphorylation of glucose‑6‑phosphate to free glucose, which can be secreted into the bloodstream.

- This step is absent in skeletal muscle, which stores glycogen but cannot release free glucose.





Gluconeogenesis (Pyruvate → Glucose)


- Key enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), fructose‑1,6‑bisphosphatase, and finally glucose‑6‑phosphatase.

- Substrates include lactate, glycerol, alanine, and other amino acids that are transported from muscle or liver to the liver.





Regulation


- Hormones: glucagon promotes gluconeogenesis; insulin inhibits it.

- Energy status: high AMP activates PEPCK transcription via CREB.






Clinical Relevance


- In diabetes, hepatic glucose production is unchecked → hyperglycemia.

- Pharmacologic inhibition of hepatic gluconeogenesis (e.g., metformin) reduces fasting glucose.




2.5 Comparative Summary



Feature Liver Kidney


Glycogen storage Yes No


Gluconeogenic capacity High Moderate


Substrate preference Lactate, alanine, glycerol Glucose, lactate, pyruvate


Hormonal regulation Insulin ↑, glucagon ↓ Similar to liver but more glucose‑dependent


Clinical relevance Diabetic hyperglycemia Hypoglycemia management


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3. Pathophysiology of Dysregulation



3.1 Hyperglycemia (Diabetes Mellitus)




Mechanism: Chronic high blood glucose leads to increased substrate availability for gluconeogenesis, particularly in the liver and kidneys.


Consequence: Elevated endogenous glucose production exacerbates hyperglycemia; insulin resistance impairs suppression of gluconeogenic enzymes.




3.2 Hypoglycemia (Insulinoma, Adrenal Insufficiency)




Mechanism: Excessive insulin secretion or cortisol deficiency reduces gluconeogenesis by downregulating PEPCK and G6Pase.


Consequence: Inability to maintain blood glucose during fasting leads to neuroglycopenia.




3.3 Metabolic Disorders (Cystic Fibrosis, Wilson’s Disease)




Mechanism: Disrupted organ function (e.g., liver dysfunction) impairs gluconeogenic capacity.


Consequence: Patients may develop hypoglycemia or require exogenous glucose supplementation.







5. Future Directions




Targeted Modulation of PEPCK and G6Pase


- Development of small‑molecule modulators that can fine‑tune enzyme activity in a tissue‑specific manner, potentially treating disorders like type 2 diabetes or hepatic encephalopathy.



Gene Therapy Approaches


- Viral vectors delivering corrected copies of PEPCK or G6Pase genes to affected tissues (liver, kidney) could ameliorate inherited deficiencies.



Metabolic Flux Imaging


- Advanced imaging techniques (e.g., hyperpolarized ^13C‑MRS) to monitor real‑time flux through gluconeogenesis and glycogenolysis pathways in vivo, enabling personalized metabolic profiling.



Integration with Circadian Regulation


- Exploring how circadian rhythms modulate PEPCK and G6Pase activity may uncover therapeutic windows for timing drug delivery or dietary interventions.



Cross‑Tissue Coordination Studies


- Investigating the interplay between liver, kidney, and adipose tissue gluconeogenic pathways could reveal novel regulatory nodes amenable to pharmacologic targeting in metabolic disorders.





Final Remarks


The intricate choreography of gluconeogenesis, glycogenolysis, and the pentose phosphate pathway underscores a sophisticated metabolic network. Central enzymes such as PEPCK, G6Pase, and G6PDH are not isolated actors but participants in a coordinated ballet that balances energy supply, redox homeostasis, nucleotide synthesis, and inter‑organ communication. Understanding this dance at both molecular and systems levels is essential for devising therapeutic strategies against metabolic diseases and for harnessing metabolic flexibility in biotechnological applications. The dynamic nature of these pathways—responsive to hormonal cues, nutrient status, and cellular demands—ensures that cells can adapt to fluctuating internal and external environments while maintaining homeostasis.