If you have done any research on aging and health recently, you have likely stumbled across the so-called anti-aging molecule, NAD. You have probably also seen it called NAD+ and maybe even as NADH. So, what is the difference, if there is any?
如果你最近做过任何关于衰老和健康的研究，你可能偶然发现了所谓的抗衰老分子 NAD。你可能也见过它被称为 NAD + ，甚至可能是 NADH。那么，如果有区别的话，又有什么区别呢？
The short answer is that there is a difference, at least between NAD and NADH. Generally speaking, when NAD is used NAD is being talked about generally. And often when using “NAD” it is referring to the specific chemical forms of NAD, NAD+ and NADH, interchangeably.
简而言之，至少 NAD 和 NADH 之间存在差异。一般来说，当 NAD 被使用的时候，NAD 是被普遍谈论的。而且通常在使用“ NAD”时，它指的是 NAD、 NAD + 和 NADH 的特定化学形式，可以互换使用。
NAD+ is written with a superscript plus (+) to designate the molecule’s charge and its specific chemical state. NADH is referring to the specific opposite chemical state that NAD can be found within your cells. A more detailed explanation is one that requires a jog down memory lane, back to the days of chemistry (more on that later).
NAD + 用上标 + (+)表示分子的电荷和特定的化学状态。NADH 指的是一种特殊的相反的化学状态，NAD 可以在你的细胞中找到。一个更加详细的解释是需要回忆的小路，回到化学的日子(更多关于那以后)。
NAD stands for nicotinamide adenine dinucleotide, which is just a fancy name describing the parts of its chemical structure. It is a molecule found in all living cells that is essential for metabolism and the proper functioning of many other key molecules as mentioned above. NAD exists in two forms: NAD+ and NADH. Its ability to switch between these two forms is what allows NAD to carry out its main function—carrying electrons from one reaction to another in the process of metabolism and energy production.
代表烟酰胺腺嘌呤二核苷酸，这只是一个花哨的名字，用来描述其化学结构的一部分。它是一种存在于所有活细胞中的分子，正如上面提到的，它对新陈代谢和许多其他关键分子的正常功能至关重要。NAD 以两种形式存在: NAD + 和 NADH。它在这两种形式之间切换的能力，使 NAD 能够发挥其主要功能ーー在新陈代谢和能量生产过程中，将电子从一个反应转移到另一个反应。
As an electron carrier, NAD+ and NADH help to convert the nutrients in your food into a form of energy your cells can use. Here’s how the process works, beginning with a quick refresher on some basic chemistry.
作为一个电子载体，NAD + 和 NADH 有助于将食物中的营养成分转化为你的细胞可以利用的能量形式。下面是这个过程的工作原理，首先我们来快速复习一下一些基本的化学知识。
The difference between NAD+ and NADH is two electrons and a hydrogen
NAD + 和 NADH 的区别是两个电子和一个氢
As you probably remember, atoms are the smallest unit of matter and molecules are just a collection of atoms held together by chemical bonds. NAD+ and NADH are considered molecules, containing the atoms carbon, hydrogen, nitrogen, oxygen, and phosphorous.
你可能还记得，原子是物质的最小单位，分子只是由化学键连接在一起的原子的集合。NAD + 和 NADH 被认为是分子，包含碳、氢、氮、氧和磷原子。
Atoms are made up of particles called protons, electrons, and neutrons. Protons carry a positive electrical charge, electrons carry a negative charge, and neutrons carry no charge. Atoms are generally neutral particles with the number of protons and electrons being equal.
The protons and neutrons are located at the center of an atom, called the nucleus. The electrons orbit around the nucleus in what are called shells or orbitals. The positively and negatively charged particles act like magnets, which is what keeps the electrons bound to the nucleus of the atom.
Ideally, an atom likes to have eight electrons in its outer shell—what is called the octet rule. Atoms are most stable when their outer shells are full and the charges are balanced. When they have fewer than eight electrons, or the charges become unequal, they become reactive. This is one reason chemical reactions take place.
In order to achieve a stable state, atoms will share their electrons. This results in chemical bonds and enables the formation of molecules, such as NAD. In its most stable state, NAD is positively charged (hence, the name NAD+). The reason being that when all the atoms making up the molecule bond together, one of the nitrogen atoms ends up with an unequal number of electrons and protons.
为了达到稳定的状态，原子会共用它们的电子。这导致了化学键的形成，使分子的形成，例如 NAD。在它最稳定的状态，NAD 是带正电的(因此，名为 NAD +)。原因在于，当组成分子的所有原子结合在一起时，其中一个氮原子的电子和质子数量不等。
Remember, on their own, atoms are neutral because they have an equal number of protons and electrons. In this case, the nitrogen atom ends up with one more proton than electrons, giving the molecule a positive charge.
NADH happens when NAD+ accepts a hydride atom—a hydrogen atom with an extra electron or two electrons total (H–). From the hydride electron pair, one electron is transferred to the positively charged nitrogen of the nicotinamide ring of NAD+, and the second hydrogen atom transferred to the C4 carbon atom opposite the nitrogen atom. The reaction is easily reversible when NADH reduces another molecule and is converted back to NAD+. This means the coenzyme can continuously cycle between the NAD+ and NADH forms without being consumed in the process. This is exactly the power of NAD.
NADH 发生在 NAD + 接受一个氢化物原子ー一个带有额外电子或总共两个电子(h -)的氢原子时。通过氢化物电子对，一个电子转移到 NAD + 烟酰胺环的正电氮上，第二个氢原子转移到氮原子对面的 C4碳原子上。当 NADH 还原另一个分子并转化为 NAD + 时，反应很容易可逆。这意味着辅酶可以在 NAD + 和 NADH 形式之间连续循环，而不会在过程中被消耗掉。这正是 NAD 的力量所在。
NAD’s role in metabolism involves giving and taking electrons
Chemical reactions will also occur if new molecules are introduced into the system, as is the case when you eat. The carbohydrates, fats, and proteins in the food you eat are all just a collection of atoms. Metabolism is the process of breaking these large molecules (often called macromolecules) into their component parts so they can be used as energy or as building blocks for cellular structures.
The chemical reactions associated with metabolism include a series of steps whereby one molecule is transformed into another molecule. This occurs as a result of redox reactions (also called oxidation-reduction reactions), which involve the transfer of electrons between molecules.
Each step is facilitated by a specific enzyme, molecules that help to accelerate chemical reactions. Oxidoreductase is the enzyme that initiates the transfer of electrons from one molecule, also called the electron donor, to another, called the electron acceptor. This group of enzymes typically uses cofactors, such as NAD, which acts as the electron acceptor. The food molecule acts as the electron donor.
Due to its chemical structure, each molecule of NAD+ can accept two electrons. This gain of electrons is called reduction, with the electrons coming in the form of a hydrogen atom. In a redox reaction, the hydrogen atom contains two electrons which it shares with the NAD+ molecule. The bond that is formed between NAD+ and H– is what creates NADH, the other form of NAD.
由于它的化学结构，NAD + 的每个分子可以接受两个电子。这种电子的获得被称为还原，即电子以氢原子的形式进入。在氧化还原反应中，氢原子含有两个与 NAD + 分子相同的电子。NAD + 和 h- 之间形成的键是 NADH 的形成，NADH 是 NAD 的另一种形式。
NADH is considered the activated carrier molecule. It acts to transfer these extra electrons to the inner membrane of the mitochondria where they are donated to a structure called the electron transport chain. Like the food molecule, NADH functions as an electron donor.
NADH 被认为是活化的载体分子。它的作用是将这些多余的电子转移到线粒体的内膜，在那里它们被捐赠给一种叫做电子传递链的结构。和食物分子一样，NADH 也是一个电子供体。
The electron transporters embedded in the mitochondrial membrane are oxidoreductases that shuttle electrons from NADH to molecular oxygen, another electron acceptor. This loss of electrons is called oxidation. NADH undergoes a reverse reaction, converting back to NAD+.
嵌入线粒体膜的电子转运体是一种氧化还原酶，负责将电子从 NADH 转移到另一种氧分子—- 电子受体。这种电子的损失被称为氧化。NADH 经历一个逆反应，转化回 NAD + 。
The process of electron transfer is coupled with the movement of protons, in the form of H+ ions, across the inner membrane. This pumping of positive charges from one side of the membrane to the other activates the protein responsible for generating ATP, the fuel used by your cells. The NAD+ that is leftover can then be reused as an electron acceptor as more food enters the system.
电子转移的过程与质子以 h + 离子的形式穿过内膜的运动耦合在一起。这种从细胞膜一侧向另一侧泵送正电荷的过程激活了负责产生 ATP 的蛋白质，ATP 是细胞所使用的燃料。当更多的食物进入系统时，剩余的 NAD + 可以作为电子受体重新使用。
NAD also has other essential functions in the cell
For example, from Wikipedia:
NAD can also activate a number of other essential enzymes in the cell.
The coenzyme NAD+ is also consumed in ADP-ribose transfer reactions. For example, enzymes called ADP-ribosyltransferases add the ADP-ribose moiety of this molecule to proteins, in a posttranslational modification called ADP-ribosylation. ADP-ribosylation involves either the addition of a single ADP-ribose moiety, in mono-ADP-ribosylation, or the transferral of ADP-ribose to proteins in long branched chains, which is called poly(ADP-ribosyl)ation. Mono-ADP-ribosylation was first identified as the mechanism of a group of bacterial toxins, notably cholera toxin, but it is also involved in normal cell signaling. Poly(ADP-ribosyl)ation is carried out by the poly(ADP-ribose) polymerases. The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance. In addition to these functions within the cell, a group of extracellular ADP-ribosyltransferases has recently been discovered, but their functions remain obscure. NAD+ may also be added onto cellular RNA as a 5′-terminal modification.
辅酶 NAD + 也被消耗在 adp- 核糖转移反应中。例如，一种叫做 adp- 核糖转移酶的酶将这种分子的 adp- 核糖部分添加到蛋白质中，这种翻译后修饰被称为 ADP核糖基化。ADP核糖基化包括单一的 adp- 核糖部分的加成，或者将 adp- 核糖转移到长支链上的蛋白质上，称为多聚(adp 核糖)。单二磷酸腺苷核糖基化首次被确定为一组细菌毒素，特别是霍乱毒素的作用机制，但它也参与正常细胞信号转导。多聚 adp 核糖(Poly (adp ribosyl)是由多聚 adp 核糖(Poly (adp riboseas)聚合酶进行的。多聚(adp- 核糖)结构参与调节多种细胞事件，在细胞核中起着重要作用，在 DNA 修复和端粒维持等过程中起着重要作用。除了细胞内的这些功能外，最近还发现了一组细胞外的 adp 核糖转移酶，但其功能仍不清楚。NAD + 也可以作为5′端修饰加入到细胞 RNA 中。
Another function of this coenzyme in cell signaling is as a precursor of cyclic ADP-ribose, which is produced from NAD+ by ADP-ribosyl cyclases, as part of a second messenger system. This molecule acts in calcium signaling by releasing calcium from intracellular stores. It does this by binding to and opening a class of calcium channels called ryanodine receptors, which are located in the membranes of organelles, such as the endoplasmic reticulum.
这种辅酶在细胞信号转导中的另一个功能是作为环状腺苷二磷酸核糖的前体，它是由腺苷二磷酸核糖 + 产生的腺苷二磷酸核糖环酶，作为第二信使系统的一部分。这种分子在钙信号中通过从细胞内贮存物质中释放钙来起作用。它通过结合和打开一类称为 ryanodine 受体的钙离子通道来实现这一目的，ryanodine 受体位于细胞器的细胞膜上，比如内质网。
NAD+ is also consumed by sirtuins, which are NAD-dependent deacetylases, such as Sir2. These enzymes act by transferring an acetyl group from their substrate protein to the ADP-ribose moiety of NAD+; this cleaves the coenzyme and releases nicotinamide and O-acetyl-ADP-ribose. The sirtuins mainly seem to be involved in regulating transcription through deacetylating histones and altering nucleosome structure. However, non-histone proteins can be deacetylated by sirtuins as well. These activities of sirtuins are particularly interesting because of their importance in the regulation of aging.
NAD + 也被去乙酰化酶消耗，这是一种依赖于 NAD- 的去乙酰化酶，如 Sir2。这些酶通过将乙酰基从底物蛋白转移到 NAD + 的 adp- 核糖部分来发挥作用，从而切断辅酶并释放烟酰胺和 o- 乙酰 -adp- 核糖。去乙酰化组蛋白主要通过去乙酰化组蛋白和改变核小体结构参与调节转录。然而，非组蛋白也可以通过去乙酰化酶来脱乙酰。这些去乙酰化酶的活动特别有趣，因为它们在衰老调节中的重要性。
Other NAD-dependent enzymes include bacterial DNA ligases, which join two DNA ends by using NAD+ as a substrate to donate an adenosine monophosphate (AMP) moiety to the 5′ phosphate of one DNA end. This intermediate is then attacked by the 3′ hydroxyl group of the other DNA end, forming a new phosphodiester bond. This contrasts with eukaryotic DNA ligases, which use ATP to form the DNA-AMP intermediate.
其他依赖 NAD- 的酶包括细菌 DNA 连接酶，它以 NAD + 为底物连接两个 DNA 末端，向一个 DNA 末端的5′磷酸基团捐赠一个单磷酸腺苷(AMP)末端。然后，这种中间体被另一端 DNA 的3′羟基攻击，形成一个新的磷酸二酯键。这与真核生物的 DNA 连接酶不同，后者利用 ATP 形成 DNA-amp 中间体。
Li et al. have found that NAD+ directly regulates protein-protein interactions. They also show that one of the causes of age-related decline in DNA repair may be increased binding of the protein DBC1 (Deleted in Breast Cancer 1) to PARP1 (poly[ADP–ribose] polymerase 1) as NAD+ levels decline during aging. Thus, the modulation of NAD+may protect against cancer, radiation, and aging.
李等人发现 NAD + 直接调节蛋白质-蛋白质的相互作用。他们还表明，随着 NAD + 水平在衰老过程中下降，导致年龄相关的 DNA 修复能力下降的原因之一，可能是 DBC1蛋白(在乳腺癌1中被删除)与 PARP1蛋白(poly [ ADP-ribose ] polymerase 1)的结合增加。因此，NAD + 的调节可以防止癌症、辐射和衰老。
NAD can also function as a cell-signaling molecule
In recent years, NAD+ has also been recognized as an extracellular signaling molecule involved in cell-to-cell communication. NAD+ is released from neurons in blood vessels,urinary bladder,large intestine, from neurosecretory cells, and from brain synaptosomes, and is proposed to be a novel neurotransmitter that transmits information from nerves to effector cells in smooth muscle organs. In plants, the extracellular nicotinamide adenine dinucleotide induces resistance to pathogen infection and the first extracellular NAD receptor has been identified. Further studies are needed to determine the underlying mechanisms of its extracellular actions and their importance for human health and life processes in other organisms.
近年来，NAD + 也被认为是参与细胞间通讯的细胞外信号分子。NAD + 从血管神经元、膀胱、大肠、神经分泌细胞和脑突触体释放，被认为是一种新型的神经递质，能将信息从神经传递到平滑肌器官的效应细胞。在植物中，细胞外的烟酰胺腺嘌呤二核苷酸诱导对病原体感染的抗性，并且第一个细胞外的 NAD 受体已经被鉴定。需要进一步的研究来确定其细胞外作用的潜在机制以及它们对人类健康和其他生物体生命过程的重要性。
NAD is a Dynamic Molecule
Many biological processes are dedicated to breaking down molecules into their component atoms so they can be reassembled into other useful molecules. Metabolism is one such process that functions to convert food into energy as well as building blocks for cell structures. Because its end products are vital to many cell functions, it is often referred to as the set of life-sustaining chemical reactions.
Part of the metabolic process involves transferring electrons between molecules. This transfer of electrons occurs as a result of redox reactions, whereby one molecule donates electrons and another molecule accepts electrons. NAD is one of the main electron carriers in redox reactions, with a unique ability to function as both a donor and an acceptor.
To perform its role as an electron carrier, NAD reverts back and forth between two forms, NAD+ and NADH. NAD+accepts electrons from food molecules, transforming it into NADH. NADH donates electrons to oxygen, converting it back to NAD+.
为了发挥其作为电子载体的作用，NAD 在 NAD + 和 NADH 两种形式之间来回转换。NAD + 接受食物分子中的电子，将其转化为 NADH。NADH 将电子转化为氧气，将氧气转化为 NAD + 。
The relative proportion of these two molecules depends on the energy state of the cell, with more NADH being present in a fed state. The NAD+:NADH ratio can act as a signal, alerting the cell to changes in its energy status. This signaling mechanism is believed to be important for the activation of a number of cellular enzymes essential toadaptive cellular responses that function to maintain cellular health.
这两个分子的相对比例取决于细胞的能量状态，更多的 NADH 处于供给状态。NADH 比值可以作为一个信号，提醒细胞能量状态的变化。这种信号机制被认为是激活许多细胞酶的重要机制，这些酶对于维持细胞健康的适应性细胞反应至关重要。2020’s Most Surprising Health Trends. 2020年最令人惊讶的健康趋势Introducing Holotropic Breathwork®.* 介绍全息呼吸法。 *