NSC 408: Nutritional Biology

Salmon Avocado Sushi RollMiso SoupGreen Tea

Diabetes

Cancer

HealthAffect

Epigenome Affect

Gene Transcription

Inflammation

Enzyme Activity

Metabolism

Nutritional Biology

Glycolysis: The process of breaking down glucose for energy. Glycogenesis: Storing glucose as glycogen in the liver and muscles. Insulin signaling pathway: The increase in blood glucose will stimulate insulin secretion from the pancreas, which will help glucose enter cells for energy production or storage. Citric Acid Cycle: Pyruvate from glycolysis is transported into the mitochondria and converted into acetyl-CoA, which is the entry point for the citric acid cycle. This cycle produces ATP. Pentose phosphate pathway: Alternative pathway for glucose metabolism that operates alongside glycolysis to produce NADPH and Ribose-5-phosphate.

CHO Upregulated Pathways:

Glycogenolysis: Process by which glycogen (a stored form of glucose) is broken down into glucose-1-phosphate and then converted to glucose-6-phosphate for energy production ​.Gluconeogenesis: Process in which the body produces glucose from non-carbohydrate sources, primarily in the liver.

CHO Downregulated Pathways:

PRO Upregulated Pathways:

Protein synthesis: Process by which amino acids are absorbed and used to build new proteins, following the instructions encoded in DNA.Amino acid catabolism: Process by which amino acids are broken down for energy production or to produce other molecules the body needs. Typically occurs when there’s an excess of amino acids or when the body needs energy and is not getting enough from carbohydrates and fats.Urea cycle: This cycle is activated to process the nitrogen byproducts from amino acid breakdown, making it safe for excretion.Citric acid cycle: Certain amino acids can be converted into intermediates like oxaloacetate, α-ketoglutarate that enter the citric acid cycle to produce ATP.

PRO Downregulated Pathways:

Proteolysis: With ample amino acids, the body will reduce proteolysis, a process of breaking down proteins into smaller peptides or amino acids.

FAT Upregulated Pathways:

Lipogenesis: Dietary fats trigger lipogenesis (formation of fat for storage), but only to a limited extent since the fat content is moderate in this meal.Beta-oxidation: Process where fatty acids are broken down to produce acetyl-CoA, which can then enter the citric acid cycle for ATP production.Citric acid cycle: Fatty acids are broken down through beta oxidation, which produces acetyl-CoA that enters the citric acid cycle to contribute to ATP production.

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FAT Downregulated Pathways:

Lipolysis: Process where stored fat is broken down for energy. This is downregulated due to the energy provided by carbohydrates and proteins.

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Organism Level

At the organism level, cancer can change the body’s metabolism due to its high demand for nutrients and energy. This often leads to what is known as cancer cachexia, a syndrome that results in weight loss, muscle wasting, and systemic inflammation.

1. Carbohydrate Metabolism

2. Protein Metabolism

3. Fat Metabolism

Cellular Level

At the cellular level, cancer cells exhibit distinct metabolic adaptations that enable their rapid growth.

1. Glucose

2. Amino Acids

3. Fatty Acids

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Organism Level

Diabetes can lead to changes in metabolism, primarily affecting how carbohydrates are processed and how insulin functions to regulate blood glucose.

1. Carbohydrate Metabolism

2. Protein Metabolism

3. Fat Metabolism

Cellular Level

Diabetes affects how cells respond to glucose and insulin. This means a meal’s components will be handled differently by the body's cells compared to a non-diabetic state.

1. Glucose

2. Amino Acids

3. Fatty Acids

1. Schell, J. (2022, May 29). Salmon Avocado Roll. Crafty Cookbook. https://www.craftycookbook.com/salmon-avocado-roll/ 2. Allrecipes Member Updated on October. (2024, October 2). Miso Soup. Allrecipes. https://www.allrecipes.com/recipe/13107/miso-soup/ 3. Iced tea recipes - japanese green tea: Hibiki-an. HIBIKI. (n.d.). https://www.hibiki-an.com/sp/contents.php/cnID/6 4. Jalili, M., et al. (2019). Soy isoflavones and cholecalciferol reduce inflammation, and gut permeability, without any effect on antioxidant capacity in irritable bowel syndrome: A randomized clinical trial. Clinical nutrition ESPEN, 34, 50–54. https://doi.org/10.1016/j.clnesp.2019.09.0035. Stojkovic, V., et al. (2017). The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial. Nutrients, 9(5), 484. https://doi.org/10.3390/nu9050484

References

6. Zivkovic, et al. (2011). Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health. California agriculture, 65(3), 106–111. https://doi.org/10.3733/ca.v065n03p106 7. Fritsche K. L. (2015). The science of fatty acids and inflammation. Advances in nutrition (Bethesda, Md.), 6(3), 293S–301S. https://doi.org/10.3945/an.114.006940 8. Riegsecker, S., et al. (2013). Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis. Life sciences, 93(8), 307–312. https://doi.org/10.1016/j.lfs.2013.07.006 9. Heshmati, J. (2021). Effect of omega-3 fatty acid supplementation on gene expression of inflammation, oxidative stress and cardiometabolic parameters: Systematic review and meta-analysis. Journal of Functional Foods, 85, 104619. https://doi.org/10.1016/j.jff.2021.104619 10. Yan, Z., et al. (2020). Antioxidant mechanism of tea polyphenols and its impact on health benefits. Animal nutrition (Zhongguo xu mu shou yi xue hui), 6(2), 115–123. https://doi.org/10.1016/j.aninu.2020.01.001

11. Balasubramanian, R., et al. (2024). Fermented foods: Harnessing their potential to modulate the microbiota-gut-brain axis for mental health. Neuroscience and biobehavioral reviews, 158, 105562. https://doi.org/10.1016/j.neubiorev.2024.105562 12. Henning, S. M., et al. (2013). Epigenetic effects of green tea polyphenols in cancer. Epigenomics, 5(6), 729–741. https://doi.org/10.2217/epi.13.57 13. Richter, C. K., et al. (2017). Total Long-Chain n-3 Fatty Acid Intake and Food Sources in the United States Compared to Recommended Intakes: NHANES 2003-2008. Lipids, 52(11), 917–927. https://doi.org/10.1007/s11745-017-4297-3 14. Psota, T. L., et al. (2006). Dietary omega-3 fatty acid intake and cardiovascular risk. The American Journal of Cardiology, 98(4), 3–18. https://doi.org/10.1016/j.amjcard.2005.12.022 15. Osdoba, K. E., et al. (2015). Using food to reduce stress: Effects of choosing meal components and preparing a meal. Food Quality and Preference, 39, 241–250. https://doi.org/10.1016/j.foodqual.2014.08.001

16. Kubicka, A., et al. (2021). More Than Meets the Eye Regarding Cancer Metabolism. International journal of molecular sciences, 22(17), 9507. https://doi.org/10.3390/ijms2217950717. Jeevanandam, M., et al. (1984). Cancer cachexia and protein metabolism. Lancet (London, England), 1(8392), 1423–1426. https://doi.org/10.1016/s0140-6736(84)91929-9https://doi.org/10.1007/BF02405382 18. Liu, X., et al. (2024). The significant role of amino acid metabolic reprogramming in cancer. Cell communication and signaling : CCS, 22(1), 380. https://doi.org/10.1186/s12964-024-01760-1 19. Bian, X., et al. (2021). Lipid metabolism and cancer. The Journal of experimental medicine, 218(1), e20201606. https://doi.org/10.1084/jem.20201606 20. Westheim, A. J. F., et al. (2023). The Modulatory Effects of Fatty Acids on Cancer Progression. Biomedicines, 11(2), 280. https://doi.org/10.3390/biomedicines11020280

21. Krause, M., & De Vito, G. (2023). Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition. Nutrients, 15(19), 4279. https://doi.org/10.3390/nu15194279 22. Leitner, B. P., et al. (2022). Insulin and cancer: a tangled web. The Biochemical journal, 479(5), 583–607. https://doi.org/10.1042/BCJ20210134 23. Felig, P., et al. (1977). Amino acid and protein metabolism in diabetes mellitus. Archives of Internal Medicine, 137(4), 507–513. https://doi.org/10.1001/archinte.1977.03630160069014 24. Paterson, M., et al. (2015). The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management. Current diabetes reports, 15(9), 61. https://doi.org/10.1007/s11892-015-0630-5 25. Abel E. D. (2010). Free fatty acid oxidation in insulin resistance and obesity. Heart and metabolism : management of the coronary patient, 48, 5–10.

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In healthy cells, insulin signals glucose transporters to facilitate glucose uptake. In type 2 diabetes, insulin resistance prevents this signaling. Glucose may not be efficiently taken up by muscle and fat cells, causing elevated blood glucose. In type 1 diabetes, glucose is unable to enter cells due to the lack of insulin, causing the body to rely more on fat and protein breakdown for energy.21,22

In diabetes, carbohydrate metabolism is affected by insulin resistance (type 2) or lack of insulin production (type 1). When a person with diabetes eats this meal, carbohydrates may lead to a rapid increase in blood glucose. In type 2 diabetes, insulin resistance makes it harder for cells to uptake glucose, causing glucose to remain elevated in the bloodstream. In type 1 diabetes, there is insufficient insulin to lower blood glucose.21,22

In diabetes, high dietary fat may worsen insulin resistance over time, especially saturated fats, though the fats in salmon and avocado are unsaturated. Fats from the meal may lead to delayed post-meal glucose spikes since fat metabolism is closely tied to glucose metabolism with diabetes.24,25

• Eating this meal often would likely be healthy due to its anti-inflammatory and nutrient-dense properties (healthy fats, lean protein, fiber, vitamins).

Health Impact of Frequent Consumption

• Frequent consumption of sushi rice (a refined carbohydrate) could elevate insulin levels and, over time, contribute to insulin resistance if not balanced with exercise or a low-glycemic diet.

• Frequent consumption of salmon could be very beneficial. About 90% of adults in the U.S. don't consume the reccommended daily amount of Omega 3 fatty Acids in their diet.13 Dietary omega-3 fatty acids have also been shown to decrease the risk of cardiovascular disease.14

• Enjoying your favorite meal could elevate mood and reduce stress due to the comforting nature of a satisfying meal.15

Proteins have a moderate effect on blood glucose. With type 1 diabetes, protein can stimulate a small insulin response and contribute to delayed glucose production. In type 2 diabetes, increased muscle protein breakdown can occur over time if glucose levels are not well-controlled.23

Cancer cells prefer glucose as their primary energy source and produce ATP through glycolysis, even with available oxygen. This method is less efficient but provides intermediates for synthesizing nucleotides, amino acids, and lipids. Carbohydrates in a cancer patient may use the tumor’s glycolytic pathway rather than being fully oxidized in the mitochondria of healthy cells.16

Epigenetic Effects

Green tea polyphenols, particularly EGCG, can influence the epigenome by inhibiting DNA methyltransferases (DNMTs), reducing methylation of tumor suppressor genes, and promoting anti-cancer gene expression.12

Miso and fermented foods may also have epigenetic effects through modulation of gut microbiota, which indirectly influences histone modification and gene expression related to inflammation and metabolism.11

Cancer & Metabolism

Cancer is a group of diseases that involve the uncontrolled growth and spread of abnormal cells in the body

But how does cancer change the metabolism of this meal?

In diabetes, high levels of glucagon can promote gluconeogenesis, leading to additional glucose production in the liver, exacerbating hyperglycemia. Insulin resistance also affects amino acid uptake and muscle protein synthesis, meaning amino acids from the meal may be used inefficiently for muscle building and repair in those with diabetes.23

SALMONContains omega-3 fatty acids, EPA and DHA, which have been shown to reduce levels of inflammatory markers.6

GREEN TEAContains the catechin epigallocatechin gallate (EGCG), which inhibits the production of pro-inflammatory cytokines.8

AVOCADOContains monounsaturated fats, carotenoids, and phytosterols which have been shown to reduce levels of inflammatory markers.7

TOFUContains Isoflavones whichhave been shown to reduce levels of inflammatory markers.4

SUSHI RICEwhite rice has a high glycemic index (GI), which can spike blood sugar and potentially lead to low-grade inflammation.5

Cancer cells also utilize fats to support rapid growth and membrane formation. Increased fat metabolism in cancer patients can lead to a depletion of stored fat, contributing to cachexia. Fat absorption from this meal might be unaffected, but the availability of these fats to healthy tissues could be limited as the tumor cells compete for these resources.19,20

Enzymes Involved In...

Glycolysis

Activated Enzymes: Hexokinase/Glucokinase, Phosphofructokinase-1, Pyruvate Kinase Inhibited Enzymes: Fructose-1,6-bisphosphatase

Glycogenesis

Activated Enzymes: Glycogen Synthase, Branching Enzyme Inhibited Enzymes: Glycogen Phosphorylase

Insulin signaling pathway

Activated Enzymes: Insulin Receptor Substrate, Protein Kinase B Inhibited Enzymes: Glycogen Phosphorylase Kinase

Citric acid cycle

Activated Enzymes: Pyruvate Dehydrogenase, α-Ketoglutarate Dehydrogenase, Citrate Synthase Inhibited Enzymes: Isocitrate Dehydrogenase

Pentose phosphate pathway

Activated Enzymes: Glucose-6-phosphate Dehydrogenase Inhibited Enzymes: 6-Phosphogluconate Dehydrogenase

Glycogenolysis

Activated Enzymes: Glycogen Phosphorylase Inhibited Enzymes: Glycogen Synthase

Gluconeogenesis

Activated Enzymes: Pyruvate Carboxylase, Phosphoenolpyruvate Carboxykinase Inhibited Enzymes: Fructose-1,6-bisphosphatase

Protein synthesis

Activated Enzymes: Aminoacyl-tRNA Synthetase, Ribosomal Enzymes, mTOR Complex Inhibited Enzymes: Autophagy-Related Enzymes

Amino acid catabolism

Activated Enzymes: Aminotransferases, Glutamate Dehydrogenase, Branched-Chain Amino Acid Transaminase, Branched-Chain Ketoacid Dehydrogenase Inhibited Enzymes: Protein Synthesis-Associated Enzymes

Urea cycle

Activated Enzymes: Carbamoyl Phosphate Synthetase I, Ornithine Transcarbamylase, Arginase Inhibited Enzymes: Ammonia-Producing Enzymes in Non-Urea Pathways

Proteolysis

Activated Enzymes: None Inhibited Enzymes: Ubiquitin-Proteasome System, Autophagy-Related Enzymes, Caspases

Lipogenesis

Activated Enzymes: Acetyl-CoA Carboxylase, Fatty Acid Synthase, Glycerol-3-Phosphate Acyltransferase Inhibited Enzymes: Hormone-Sensitive Lipase

Beta-oxidation

Activated Enzymes: Carnitine Palmitoyltransferase I, Acyl-CoA Dehydrogenase, 3-Hydroxyacyl-CoA Dehydrogenase Inhibited Enzymes: Acetyl-CoA Carboxylase

Lipolysis

Activated Enzymes: None Inhibited Enzymes: Hormone-Sensitive Lipase, Perilipin

Cancer patients often experience increased protein breakdown and reduced protein synthesis, as tumors release inflammatory cytokines that can cause muscle breakdown and interfere with normal protein metabolism. Protein digestion and absorption may remain relatively normal, but the body’s ability to utilize proteins for building tissues is impaired.17,18

Carbohydrate Metabolism(Sushi rice + Miso paste)

Upregulated pathways

Downregulated pathways

Protein Metabolism(Salmon + Tofu)

Upregulated pathways

Downregulated pathways

Fat Metabolism(Salmon + Avocado)

Upregulated pathways

Downregulated pathways

Cancer cells require amino acids for protein synthesis, nucleotide synthesis, and signaling pathways that support their growth. They often increase the uptake of amino acids like glutamine, to support the tricarboxylic acid (TCA) cycle. This means that amino acids from the meal might be more rapidly consumed for growth rather than repair.17,18

Cancer cells use fatty acids to create phospholipids for cell membrane synthesis or undergo β-oxidation to generate energy. Some cancers can even create new fatty acids for structural and signaling purposes. The fatty acids from the meal could be taken up by cancer cells and utilized in these pathways, supporting their growth.19,20

In type 2 diabetes, cells have a higher reliance on fat metabolism, as glucose uptake is impaired. Increased fatty acid oxidation in cells further impair insulin signaling and lead to the buildup of toxic byproducts. In type 1 diabetes, fatty acid oxidation is elevated when blood glucose can't be used for energy, leading to higher ketone body production, which can increase the risk of diabetic ketoacidosis if insulin levels remain low.24,25

1. Carbohydrate Metabolism

1. Carbohydrate Metabolism

1. Carbohydrate Metabolism

Cancer cells rely on glucose through aerobic glycolysis. This can lead to higher glucose consumption by the tumor, depriving other tissues of glucose and causing an overall increase in glucose demand in the body.16 As a result, blood glucose levels will fluctuate more in cancer patients, potentially leading to altered insulin responses after carbohydrate intake.

Salmon Avocado Roll 1

• Sushi rice, rice vinegar, dry seaweed sheets, raw salmon, avocado slices

Ingredients

Miso Soup 2

• Miso paste, dashi broth, tofu, green onions

Green Tea 3

• Sencha green tea leaves, water

Diabetes & Metabolism

Diabetes is a chronic disease that occurs when the body is unable to produce or use insulin properly, resulting in high blood sugar levels

But how does diabetes change the metabolism of this meal?

Gene TranscriptionInfluences

Omega-3 fatty acids from salmon can influence gene transcription by activating PPAR-α receptors, leading to increased fatty acid oxidation and reduced fat storage.9

Green tea polyphenols have been shown to modulate gene expression related to antioxidant defense systems, potentially increasing NRF2 activity, which enhances antioxidant gene transcription.10