ビリルビン代謝の概要 肝臓の構造および機能 執筆者： Steven K. Herrine , MD, Sidney Kimmel Medical College at Thomas Jefferson University 医学的にレビューされた 2018年 1月 MSDマニュアルプロフェッショナル版
What you are is what you eat.という言葉があります。自分が食べたものが自分の体になるということです。どんなものをどれくらいの量食べればいいのか？その答えは生化学が教えてくれます。
参考
生化学biochemistryとよばれる学問分野は、歴史の長い生物学biologyや医学medicine (or medical science)と化学chemistryという異なる学術領域をミックスさせた学際的な出自をもつ、比較的あたらしい分野です。ちなみに、生化学分野おいて歴史的も内容的にも最も有名な学術雑誌The Journal of Biological Chemistryの創刊は1905年です。生化学では、生体のもつ分子（生体分子）の化学構造を決定し、生体中で起こっている化学反応（生化学反応）をひとつひとつあきらかにしてゆくことを勃興当時の中心テーマとしていました。やがて、生化学反応をつかさどる酵素enzymeの本体がタンパク質であることがわかってくると、タンパク質を分離・解析して、タンパク質の機能をあきらかにすることも大きなテーマとなってきました。そして、タンパク質の設計図は遺伝子が担うことも知られるようになり、生化学反応と遺伝子との関連をみいだしてしていくことも生化学が取り組む重要な課題となってきています。（https://www.niid.go.jp/niid/ja/from-biochem/3263-2013-02-25-07-34-02.html）
More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones. Int J Mol Sci. 2019 Dec; 20(24): 6124. Published online 2019 Dec 4. doi: 10.3390/ijms20246124 PMCID: PMC6941031 PMID: 31817290 There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low.
During a fast, the liver is flooded with fatty acids mobilized from adipose tissue. The resulting elevation of acetyl CoA produced by fatty acid oxidation inhibits pyruvate dehydrogenase and activates pyruvate carboxylase (PC). The OAA (Oxaloacetic acid) produced by PC is used by the liver for gluconeogenesis rather than for the TCA cycle. Additionally, fatty acid oxidation decreases the NAD+/NADH ratio, and the rise in NDAH shifts OAA to malate. The decreased availability of OAA for condensation with acetyl CoA results in the increased use of acetyl CoA for ketone body synthesis.
ATP release from damaged cells and tissues has recently attracted attention, and has been reported as an alarm signal compound, alarmin. ‥ The released ATP in serum, however, is rapidly degraded within few minutes (Blood Lactate/ATP Ratio, as an Alarm Index and Real-Time Biomarker in Critical Illness April 5, 2013 PLOS ONE https://doi.org/10.1371/journal.pone.0060561)
Ketosis, ketogenic diet and food intake control: A complex relationship February 2015Frontiers in Psychology 6:27 Follow journal DOI: 10.3389/fpsyg.2015.00027Nutrient-sensitive neurons reacting to glucose but also to fatty acids (FAs) concentrations are present at many sites throughout the brain and may play a key role in the neural control of energy and glucose homoeostasis.
FUEL METABOLISM IN STARVATION George F. Cahill, Jr. Annu. Rev. Nutr. 2006. 26:1–22 doi: 10.1146/annurev.nutr.26.061505.111258
Ketone Strong: Emerging evidence for a therapeutic role of ketone bodies in neurological and neurodegenerative diseases Thomas N. SeyfriedJournal of Lipid Research VOLUME 55, ISSUE 9, P1815-1817, SEPTEMBER 01, 2014 DOI:https://doi.org/10.1194/jlr.E052944
Paula Yurkanis Bruice『Organic Chemistry 8th edition』Chapter 23 The Organic CHemistry of the Coenzymes, COmpouds Derived from Vitamins page 1142~page 1143 23.6 VITMIN B12: THE VITAMIN NEEDED FOR CERTAIN ISOMERIZATIONS
Figure 1. Anatomical organization of the pancreas Published: 11 March 2016 Pancreatic regulation of glucose homeostasis Experimental & Molecular Medicine volume 48, pagee219 (2016) 膵臓、膵島、α細胞、β細胞がわかりやすく図示されている。
Why is the reaction glucose to glucose 6-phosphate mediated by hexokinase not reversible in glyconeogenesis? (https://chat.openai.com/chat) The reaction of glucose to glucose-6-phosphate, which is catalyzed by hexokinase, is an irreversible step in glycolysis. This reaction is also not reversible in gluconeogenesis. One of the main reasons for this irreversibility is the large negative free energy change that occurs during the hexokinase-catalyzed reaction. The hydrolysis of ATP that occurs during this reaction releases a large amount of free energy, making the reaction highly exergonic. This energy is then used to drive the formation of glucose-6-phosphate. In addition, glucose-6-phosphate is trapped within the cell since it cannot diffuse across the plasma membrane due to its negative charge. In gluconeogenesis, glucose-6-phosphate is produced from fructose-6-phosphate through a different enzyme called glucose-6-phosphatase. This enzyme catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate, which allows glucose to be released from the cell and transported to other tissues.
Overall, the irreversible nature of the hexokinase-catalyzed reaction is an important feature of glucose metabolism, as it ensures that glucose is rapidly and efficiently converted to glucose-6-phosphate for energy production, and that glucose-6-phosphate is effectively trapped within the cell for further metabolism.
質問：When alanine is preferred and when lactate is prefferred in gluconeogenesis as a starting materials?
回答：
In gluconeogenesis, both alanine and lactate can be used as starting materials for glucose synthesis, but their utilization is dependent on the specific metabolic conditions. Alanine is typically preferred as a starting material in gluconeogenesis when there is a high demand for glucose and when amino acids are being mobilized from muscle tissue. During intense exercise or prolonged fasting, skeletal muscle breaks down protein to release amino acids, including alanine. Alanine is then transported to the liver where it is converted to pyruvate and used in gluconeogenesis to produce glucose. The conversion of alanine to pyruvate also generates ammonium ions, which can be incorporated into the urea cycle and excreted in urine. Thus, alanine is an important source of both glucose and nitrogen during times of high energy demand. Lactate, on the other hand, is preferred as a starting material in gluconeogenesis when there is a high demand for glucose and a shortage of oxygen. During intense exercise, the demand for ATP exceeds the supply of oxygen, leading to the production of lactate via anaerobic metabolism. Lactate is then transported to the liver, where it is converted to pyruvate and used in gluconeogenesis to produce glucose. This process is important for maintaining blood glucose levels during periods of intense exercise or hypoxia.
Overall, the utilization of alanine or lactate in gluconeogenesis is dependent on the metabolic state of the organism and the specific demands for glucose production.
質問：What is the difference between glucose-alanine cycle and glucose-lactate cycle?
回答：
The glucose-alanine cycle and the glucose-lactate cycle are two different metabolic pathways that occur in the body during periods of intense exercise or prolonged fasting.
The glucose-alanine cycle, also known as the Cori cycle, is a metabolic pathway that occurs in the liver and skeletal muscles. During periods of intense exercise, skeletal muscles break down glycogen to produce glucose. The glucose is then transported to the liver, where it is converted to pyruvate and then to alanine, which is released into the bloodstream. The alanine is transported back to the skeletal muscles, where it is converted back to pyruvate and used to regenerate glucose through gluconeogenesis. The glucose is then transported back to the liver, completing the cycle. ん？よくわからないせつめい。
In contrast, the glucose-lactate cycle, also known as the Lactic acid cycle, is a metabolic pathway that occurs in the skeletal muscles. During periods of intense exercise, the skeletal muscles break down glycogen to produce glucose, which is then converted to pyruvate through glycolysis. Under conditions of low oxygen, pyruvate is converted to lactate instead of being further metabolized to produce energy. The lactate is then transported to the liver, where it can be converted back to glucose through gluconeogenesis.
The key difference between the two cycles is the end product that is transported from the muscles to the liver. In the glucose-alanine cycle, alanine is transported, whereas in the glucose-lactate cycle, lactate is transported. Additionally, the glucose-lactate cycle occurs entirely within the skeletal muscles and liver, while the glucose-alanine cycle occurs between the liver and skeletal muscles. これもよくわからない説明
Endothelial Transcytosis of Insulin: Does It Contribute to Insulin Resistance? Warren L. Lee and Amira Klip 10 AUG 2016 https://doi.org/10.1152/physiol.00010.2016insulin must exit capillaries, which (in tissues like skeletal muscle and fat) are lined by a layer of continuous endothelium. Insulin must therefore pass between endothelial cells (paracellular diffusion, green arrow) or be transported across individual cells by transcytosis (red arrow) to access the interstitium.
In the human body, glucose uptake is accomplished via two mechanisms, insulin mediatedglucose uptake (IMGU), which occurs only in insulin-sensitive tissues (i.e. liver, muscle and adipocytes) and non-insulin mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and non-insulin-sensitive tissues (i.e., brain, blood cells, nerve, etc.).
GLUT1 is insulin-independent and is widely distributed in different tissues. GLUT4 is insulin-dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions.
GLUTs 1, 3, and 4 are transporters that have high affinity for glucose ranging in Km of 2–5 mM glucose. Consequently, the functions of these transporters align with the physiological concentration of glucose of about 5 mM. On the other hand, GLUT2 has a low affinity for glucose with its Km of about 15–20 mM glucose. GLUT2, therefore, is able to move glucose into the liver cell and the pancreatic beta cell in proportion to the plasma level of glucose.
An auxiliary function of some GLUTs in the liver seems to be the transport of dehydroascorbic acid (DHA), the oxidized form of ascorbic acid (AA, vitamin C) as described for the GLUT isoforms GLUT1, GLUT3, and GLUT4 [188]. The last-mentioned glucose transporter GLUT4 is known as major isoform in muscular and adipose tissues and only shows minor expression levels in the liver as well [228].
GLUT-2 (SLC2A2) also transports other dietary sugars such as galactose, mannose and fructose with a high affinity for glucosamine[11,24,25]. GLUT-2 is highly expressed in the liver, pancreatic beta cells, and on the basolateral surface of kidney and small intestine epithelia[26,27] with expression regulated by sugars and hormones[23,28].