Author: Shenzhou

Reviewer: Weiming

  Blood is a fluid tissue that circulates through the human cardiovascular system. Its chief role is to transport substances, and it consists mainly of plasma, blood cells, and platelets. Red and white blood cells are crucial to transport and defense against foreign invaders, respectively. Platelets are cell fragments produced by megakaryocytes in the bone marrow and are essential for hemostasis. This article introduces the metabolic features of these three cellular components.

Red blood cell metabolism

  Red blood cells are among the most important cells in the blood. They arise in the bone marrow through the committed differentiation of hematopoietic stem cells, passing through the proerythroblast, early erythroblast, intermediate erythroblast, late erythroblast, and reticulocyte stages before becoming mature erythrocytes. During maturation, they undergo a series of changes in both metabolic function and morphology.

  Before mammalian red blood cells are fully mature, they can still synthesize DNA and RNA, proteins, and lipids, and can carry out the tricarboxylic acid cycle and oxidative phosphorylation. Once fully mature, however, they retain only glycolysis and the pentose phosphate pathway. Apart from a plasma membrane and cytoplasm, a mature mammalian erythrocyte has neither a nucleus nor organelles such as mitochondria, so its metabolism is simpler than that of most cells. Glucose remains its principal energy source. Red blood cells take up about 30 g of glucose from the plasma each day; most is metabolized through glycolysis or the 2,3-bisphosphoglycerate (2,3-BPG) shunt, while only 5%–10% enters the pentose phosphate pathway.

  The 2,3-BPG shunt is a pathway unique to red-cell glycolysis. In this shunt, 1,3-bisphosphoglycerate (1,3-BPG), produced from glucose during glycolysis, is not converted directly into 3-phosphoglycerate by phosphoglycerate kinase. Instead, bisphosphoglycerate mutase converts it into 2,3-BPG, which is then converted into 3-phosphoglycerate. The shunt’s main function is to regulate oxygen transport by red blood cells: the body can adjust oxygen delivery to tissues by changing the concentration of 2,3-BPG in these cells.

  The pentose phosphate pathway in red blood cells is the same as in other cells and mainly produces NADPH+H+. NADPH and NADH are important reducing equivalents in erythrocytes. They protect membrane proteins, hemoglobin, and enzymes from oxidation, thereby preserving normal red-cell function.

  Because red blood cells have no mitochondria, they cannot synthesize fatty acids de novo, yet renewal of their membrane lipids is essential to their survival. They therefore exchange lipids continuously with the plasma through active uptake and passive exchange, maintaining a normal lipid composition.

White blood cell metabolism

  Human white blood cells fall mainly into three systems: granulocytes, lymphocytes, and monocytes/macrophages. Their principal function is to defend the body against foreign invaders.

  Granulocytes contain very few mitochondria, so glycolysis remains their main source of energy. Monocytes and macrophages can carry out aerobic oxidation, but glycolysis still accounts for a large share of their energy metabolism. Lymphocytes, by contrast, have different metabolic profiles at different stages. During an immune response, for example, T lymphocytes obtain most of their energy through aerobic glucose oxidation before activation, but switch to glycolysis after activation.

  Monocytes/macrophages and lymphocytes can also synthesize a range of bioactive proteins to perform their various functions. Monocytes and macrophages, for example, produce many enzymes, complement components, and cytokines. During an immune response, plasma cells differentiated from B lymphocytes produce antibodies that participate in humoral immunity. Mature granulocytes, however, lack endoplasmic reticulum and therefore synthesize very little protein.

Platelet metabolism

  Platelets are produced by mature megakaryocytes. Numerous invaginations first form on the surface of a mature megakaryocyte and converge within the cell, partitioning off portions of cytoplasm. These fragments enter the circulation through the sinusoids of the hematopoietic tissue in the bone marrow.

  Although glycolysis also supplies most of a platelet’s energy, inhibiting either glycolysis or mitochondrial electron transport alone does not disrupt platelet activation. Activation is markedly impaired only when both processes are inhibited. Glycolysis and aerobic oxidation therefore complement one another in platelet metabolism.