1. Dr. Ir. Happy Nursyam, MS Week: 5 Metabolism – Products and Exchanges Fats/Lipids

2. Metabolism – Products and Exchanges Fats/Lipids Liver – Conversions via Krebs from AAs, Glucose, FAs to FAs Liver – Formation of Lipoproteins Blood – Movement as FAs, Glycerol Adipose – Release as Glycerol and FAs Adipose – Conversion to Mobile FA Form TAG Lipase at Adipose

3. Metabolism – Products and Exchanges Fats/Lipids Some Considerations Triacylglycerol (TAG) Lipase and Insulin serve as key regulators for control, primarily anabolic pathway Fish (Carnivores for Sure) are Hyperinsulinemic (High Insulin)

4. Metabolism – Products and Exchanges Fats/Lipids Anomalies Starvation –Insulin/Glucagon Balance shifts triggering –Hormones sensitive lipases and glucocorticosteriods –Gluconeogenesis –Elevated Proteolysis

5. Starvation Continued Prolonged Starvation- Leads to Fatty Liver Syndrome and Ketosis Like Toxemia Generalizations –High carbohydrate intake elevates enzymes, insulin and TAG Lipase –Epidermal Growth Factor elevated, resulting in elevated brain storage of fats –Growth hormone responds to intake Acute vs. Chronic Chronic – Protein Usage – Carbohydrate Sparing Chronic – Decreased Lipogenesis, Increased Lypolysis Acute – Above Reversed and Growth Hormone Acts Like Insulin

6. Metabolism – Products and Exchanges Proteins 1 Protein Recycling a Normal Internal Cellular Process 2 Net Growth – Turnover and Degradation Balanced with or Less than Assimilation Providing Growth 3 Metabolic Maintenance – Synthesis and Degradation are Balanced, Synthesis via all Routes Protein Degradation and Synthesis 1, 2, 3 are Energy Dependent Pathways

7. Metabolism – Products and Exchanges Protein Aging Primary – Dipeptide Bonds Secondary – Hydrogen Bonds Tertiary – Disulfide Bonds (β Pleated and Globular Quaternary – Disulfide Bonds (Usually Dimers and tetramers)

8. Metabolism – Products and Exchanges Protein Aging Continued Processes –Oxygen Radicals – Break Disulfide and Hydrogen Bonds –Deamination – Break Amide Bonds –Proteases (Ca+ Dependent, Leak from Lysosomes) –Ubiquitin – Attaches Protein, Complex Fuses with Lysosomes and Stored or Expelled, So Called Heat Shock Proteings –High Glucose – Increased Oxygen Radical Formation

9. Metabolism – Products and Exchanges Protein Cycling Proteins Constantly Removed and Replaced –23 to 42% elevation of 0 2 consumption in Atlantic Cod a Carnivore –11 to 22% elevation of O 2 consumption in Carp a Herbivore –Tissue Demands (Table 2) Cyclohexamide synthesis – 80% O 2 consumption in hepatocytes Turnover rates vary – high in hepatocytes, low in muscle Go Back to Synthesis

10. Metabolism – Products and Exchanges Protein Synthesis The Process –Transcription –Translation –Secondary Modification

11. Metabolism – Products and Exchanges Protein Dynamics Muscle – Primarily Post Mitotic, No Replacement with New Cells Serves as Primary Protein Storage Site While Protein Synthesis and Exchange are Low, Muscle Accounts for 50 to 80% of Body Mass Go to Table 2A (Atlantic Cod at 300g) TissueGrowth 0%Growth 1%Efficiency 1% Gill4.410.110% White Muscle.46%1.94%50%

12. Metabolism – Products and Exchanges Protein Dynamics (Figure 2) % Consumption Protein Synthesis Protein Growth Synthesis Growth

13. Metabolism – Products and Exchanges Protein Dynamics Related to Bioenergetics Basic Bioenergetics Equation Consumption = Growth – Respiration – Waste or C = G – R – W Expanded Equation Consumption = Growth – Standard Metabolism – Activity – Digestion – Feces – Urine Or C = G – R S – R A – R D – F – U Note: RS, RA, RD are Specific Dynamic Action Therefore the equation could be presented as C+ G – S – F – U S = Specific Dynamic Action as Measured by O 2 Uptake

14. Metabolism – Products and Exchanges Protein Dynamics – SDA Continued Considerations Specific Dynamic Action Function of –Digestion –Gut Motility –Enzyme Synthesis –Absorption Clear Link to Essential Amino Acids (EAAs) –See Table 2B –Protein Synthesis Linked to Precursors –Gluconeogenesis and Lipogenesis Minor Processes –EAAs are Limiting

15. Metabolism – Products and Exchanges Protein Dynamics (Table 2B) Fractional Rate of Protein Synthesis TissueSalineEAAIncrease Liver39.50%78.10%2 - Fold White Muscle0.98%2.29%2 to 3 Fold

16. Metabolism – Products and Exchanges Protein Dynamics Outcomes Due to Metabolic Shifts Energetics Related to Reproduction ie Vitellogen Production Response to Disease –Cellular Response ie Oxidative Burst –Antibody Production Contaminant Induction –P450 Production Competes with Other Biosynthetic Pathways

17. Control of Feeding Genotypic Influences Social Interactions – Pecking Order Food Constituents – EFAs Endogenous Factors – Such as: –Cholecystokinin (CCK) –Bombesin – Gastrin releasing peptide –Neuropeptides (Brain and Pancreas) NPY for example Not proven in fish, but known for mammals Can regulate growth via –Stimulant –Lignand of receptors for release of GH –Stimulator for GH release via GnRH which stimulates somatotrophs

18. Growth Hormone (GH) Single-chain peptide Produced and stored in somatotroph cells of the pituitary Similar to those of prolactin and somatolactin thus included in the GH/prolactin family of hormones Assumes central role in the growth of fish Has osmoregulatory function as well

19. GH Continued Neuropeptide Y (NPY), Growth hormone releasing hormone (GHRH) and Gonadotropin releasing hormone (GnRH) major stimulating hormones Somatotropin release- inhibiting factor major inhibiting hormone Se figure 3 for other factors influencing the release of GH Somatotroph Cell of Pituitary NPY GHRH GnRH + + SRIF - + GH Release

20. GH Continued Patterns of Release –Pulse as in Carp –Episodic as in Trout –Diurnal as in mammals? Degradation –Short lived 10 to 45 minutes depending of fish species Responds to physiological state of the fish –Stress increases production

21. Physiological Response to GH Starvation Starved fish have higher GH levels than fed Both fed and starved will show a persistent decreased GH in response to cortisol levels in short term stress situations Chronic stress results in elevated GH levels Example – Yearling Coho salmon, held in fresh have depressed GH

22. GH in Mammals GH secretion amplitude (amount) and frequency dictate level of activity Number of receptors regulate level of action Number of receptors are under feed back to GH level GH binding protein serves a reservoir for GH

23. Tissue Action of GH Miss Me? Liver – Increase Activity Related to Protein, Fat and Carbohydrate Utilization Muscle – Increased Biosynthesis Intestine – Increase in Amino Acid Mobilization and Protein Synthesis Thyroid – Increased T4 Release Cartilage – Increased Proteoglycan synthesis and Sulfate Uptake Kidney – Increase GH Receptors, Cell Volume and Osmoregulation