Population history of China

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Population_history_of_China 

The population history of China covers the long-term pattern of population growth in China and its impact on the history of China. The population went through many cycles that generally reached peaks along each imperial power and was decimated due to wars and barbarian invasions. The census data shows that the population as percentage share of the world has a long-term average of 26%, with 6% standard deviation. The minimum could be as low as 16% while the maximum as high as 33%. In the late 20th century and the early 21st century, the percentage share has been trending down. This was caused by two opposite factors: On one hand, the world population has been growing explosively. On the other hand, in order to address the poverty issue, China implemented a strict birth control policy. For recent trends see demographics of China and China.

Census data

Period	Year	Census Households	Census Population	Modern estimates	Share of World population
Warring States	-423			43,740,000	27%
Western Han	-200			42,000,000	28%
Western Han	1	12,366,470	59,594,979	65,000,000	30%
Eastern Han	156	16,070,906	50,068,856	65,000,000	31%
Eastern Han	200			60,800,000	32%
Western Jin	280	6,801,000	8,200,000	37,986,000	20%
Western Jin	300			35,000,000	18%
Sixteen Kingdoms	400			51,300,000	27%
Northern and Southern dynasties	500			51,300,000	17%
Sui	600	8,700,000	44,500,000	46,000,000	23%
Tang	700	6,156,141	37,140,001	48,300,000	23%
Tang	755	8,914,709	52,919,309	90,000,000	15%
Tang	800			50,600,000	11.92%
Tang	900			39,000,000	16%
Northern Song	1000			60,950,000	23%
Northern Song	1100			110,750,000	21.67%
Southern Song	1200			140,000,000	28.33%
Yuan	1290	13,196,206	58,834,711	75,306,000	20%
Yuan	1351	27,650,000	87,587,000	120,359,000	30%
Ming	1393	10,699,399	58,323,934	65,000,000	19%
Ming	1400	11,415,829	66,598,339	81,000,000	23%
Ming	1500	10,508,935	60,105,835	110,000,000	26%
Ming	1550	10,621,436	60,692,856	145,000,000	29.17%
Ming	1600			197,000,000	32.83%
Qing	1650		123,000,000	140,000,000	21.54%
Qing	1700		126,110,000	160,000,000	22.86%
Qing	1750		181,810,000	225,000,000	25.85%
Qing	1800		297,623,950	330,000,000	30.4%
Qing	1850		430,000,000	436,100,000	33.05%
Republic of China	1928		474,780,000	474,780,000	24%
People's Republic of China	1950		546,815,000	552,000,000	22%
PRC	1975		916,395,000	920,940,000	23%
PRC	1982		1,008,180,000	1,022,250,000	22%
PRC	2000		1,262,645,000	1,283,190,000	21%
PRC	2005		1,303,720,000	1,321,620,000	20%
PRC	2010		1,337,825,000	1,359,760,000	20%
PRC	2015		1,374,620,000	1,397,030,000	19%
PRC	2020		1,411,778,724	1,447,084,648	17.8%

Han, 202 BC – 220 AD

Further information: Society and culture of the Han dynasty

 

A painted ceramic architectural model—found in a Han tomb—depicting an urban residential tower with verandas, tiled rooftops, dougong support brackets, and a covered bridge extending from the third floor to another tower

During the Warring States period (403–221 BC), the development of private commerce, new trade routes, handicraft industries, and a money economy led to the growth of new urban centers. These centers were markedly different from the older cities, which had merely served as power bases for the nobility. The use of a standardized, nationwide currency during the Qin dynasty (221–206 BC) facilitated long-distance trade between cities. Many Han cities grew large: the Western Han capital, Chang'an, had approximately 250,000 inhabitants, while the Eastern Han capital, Luoyang, had approximately 500,000 inhabitants. The population of the Han Empire, recorded in the tax census of 2 AD, was 57.6 million people in 12,366,470 households. The majority of commoners who populated the cities lived in extended urban and suburban areas outside the city walls and gatehouses.

Trends: Tang to Southern Song

Demographic historian Angus Maddison uses extensive data to argue that the main base of the Chinese economy shifted southwards between about 750 AD and 1250 AD. In 750 three quarters of the population lived in the rural north, growing wheat and millet. By about 1250 three quarters lived south of the Yangtze and grew mainly rice. By 1000 AD per capita income in China was higher than the Europe average at the same time. Divergence took place from fifteenth and eighteenth centuries as the European economy grew faster. From 1250 to 1900 China saw a fourfold increase in population whilst maintaining an average per capita income more or less stable. The main explanation were peace, irrigation and fast ripening seeds that permitted two crops a year. Chinese total GDP grew faster than that of western Europe from 1700 to 1820, even though European per capita income grew faster.

Ming, 1368 – 1644

Sinologist historians debate the population figures for each era in the Ming dynasty. The historian Timothy Brook notes that the Ming government census figures are dubious since fiscal obligations prompted many families to underreport the number of people in their households and many county officials to underreport the number of households in their jurisdiction. Children were often underreported, especially female children, as shown by skewed population statistics throughout the Ming. Even adult women were underreported; for example, the Daming Prefecture in North Zhili reported a population of 378,167 males and 226,982 females in 1502. The government attempted to revise the census figures using estimates of the expected average number of people in each household, but this did not solve the widespread problem of tax registration. Some part of the gender imbalance may be attributed to the practice of female infanticide. The practice is well documented in China, going back over two thousand years, and it was described as "rampant" and "practiced by almost every family" by contemporary authors. However, the dramatically skewed sex ratios, which many counties reported exceeding 2:1 by 1586, cannot likely be explained by infanticide alone.

The Xuande Emperor (r. 1425–35); he mistakenly stated in 1428 that his populace was dwindling due to palace construction and military adventures. But the population was rising under him, a fact noted in a 1432 report.

The number of people counted in the census of 1381 was 59,873,305; however, this number dropped significantly when the government found that some 3 million people were missing from the tax census of 1391. Even though underreporting figures was made a capital crime in 1381, the need for survival pushed many to abandon the tax registration and wander from their region, where Hongwu had attempted to impose rigid immobility on the populace. The government tried to mitigate this by creating their own conservative estimate of 60,545,812 people in 1393. In his Studies on the Population of China, Ho Ping-ti suggests revising the 1393 census to 65 million people, noting that large areas of North China and frontier areas were not counted in that census. Brook states that the population figures gathered in the official censuses after 1393 ranged between 51 and 62 million, while the population was in fact increasing. Even the Hongzhi Emperor (r. 1487–1505) remarked that the daily increase in subjects coincided with the daily dwindling amount of registered civilians and soldiers. William Atwell states that around 1400 the population of China was perhaps 90 million people, citing Heijdra and Mote.

Historians are now turning to local gazetteers of Ming China for clues that would show consistent growth in population. Using the gazetteers, Brook estimates that the overall population under the Chenghua Emperor (r. 1464–87) was roughly 75 million, despite mid-Ming census figures hovering around 62 million. While prefectures across the empire in the mid-Ming period were reporting either a drop in or stagnant population size, local gazetteers reported massive amounts of incoming vagrant workers with not enough good cultivated land for them to till, so that many would become drifters, conmen, or wood-cutters that contributed to deforestation. The Hongzhi and Zhengde emperors lessened the penalties against those who had fled their home region, while the Jiajing Emperor (r. 1521–67) finally had officials register migrants wherever they had moved or fled in order to bring in more revenues.

Even with the Jiajing reforms to document migrant workers and merchants, by the late Ming era the government census still did not accurately reflect the enormous growth in population. Gazetteers across the empire noted this and made their own estimations of the overall population in the Ming, some guessing that it had doubled, tripled, or even grown fivefold since 1368. Fairbank estimates that the population was perhaps 160 million in the late Ming dynasty, while Brook estimates 175 million, and Ebrey states perhaps as large as 200 million. However, a great epidemic that entered China through the northwest in 1641 ravaged the densely populated areas along the Grand Canal; a gazetteer in northern Zhejiang noted more than half the population fell ill that year and that 90% of the local populace in one area was dead by 1642.

Qing, 1636 – 1912

The most significant facts of early and mid-Qing social history was growth in population, population density, and mobility. The population in 1700, according to widely accepted estimates, was roughly 150 million, about what it had been under the late Ming a century before, then doubled over the next century, and reached a height of 450 million on the eve of the Taiping Rebellion in 1850. The food supply increased due to better irrigation and especially the introduction of fast-maturing rice seeds, which permitted harvesting two or even three crops a year on the same land. An additional factor was the spread of New World crops like peanuts, potatoes, and especially sweet potatoes. They helped to sustain the people during shortages of harvest for crops such as rice or wheat. These crops could be grown under harsher conditions, and thus were cheaper as well, which led to them becoming staples for poorer farmers, decreasing the number of deaths from malnutrition. Diseases such as smallpox, widespread in the seventeenth century, were brought under control by an increase in inoculations. In addition, infant deaths were also greatly decreased due to improvements in birthing techniques and childcare performed by midwives and doctors. Government campaigns lowered the incidence of infanticide. Unlike Europe, where numerical growth in this period was greatest in the cities, in China the growth in cities and the lower Yangzi was low. The greatest growth was in the borderlands and the highlands, where farmers could clear large tracts of marshlands and forests.

The population was also remarkably mobile, perhaps more so than at any time in Chinese history. Indeed, the Qing government did far more to encourage mobility than to discourage it. Millions of Han Chinese migrated to Yunnan and Guizhou in the 18th century, and also to Taiwan. After the conquests of the 1750s and 1760s, the court organized agricultural colonies in Xinjiang. Migration might be permanent, for resettlement, or the migrants (in theory at least) might regard the move as a sojourn. The latter included an increasingly large and mobile workforce. Local-origin-based merchant groups also moved freely. This mobility also included the organized movement of Qing subjects overseas, largely to Southeastern Asia, in search of trade and other economic opportunities.

Famines

See also: Northern Chinese Famine of 1876–1879, Chinese famine of 1928–1930, and Chinese famine of 1942–1943

 

Chinese officials engaged in famine relief, 19th-century engraving

Chinese scholars had kept count of 1,828 instances of famine from 108 BC to 1911 in one province or another—an average of close to one famine per year. From 1333 to 1337 a famine in the north killed 6 million Chinese. The four famines of 1810, 1811, 1846, and 1849 cost perhaps 45 million lives.

The period from 1850 to 1873 saw, as a result of the Taiping Rebellion, drought, and famine, the population of China drop by over 30 million people. China's Qing Dynasty bureaucracy, which devoted extensive attention to minimizing famines, is credited with averting a series of famines following El Niño-Southern Oscillation-linked droughts and floods. These events are comparable, though somewhat smaller in scale, to the ecological trigger events of China's vast 19th-century famines. Qing China carried out its relief efforts, which included vast shipments of food, a requirement that the rich open their storehouses to the poor, and price regulation, as part of a state guarantee of subsistence to the peasantry (known as ming-sheng).

When a stressed monarchy shifted from state management and direct shipments of grain to monetary charity in the mid-19th century, the system broke down. Thus the 1867–68 famine under the Tongzhi Restoration was successfully relieved but the Great North China Famine of 1877–78, caused by drought across northern China, was a catastrophe. The province of Shanxi was substantially depopulated as grains ran out, and desperately starving people stripped forests, fields, and their very houses for food. Estimated mortality is 9.5 to 13 million people.

Great Leap Forward: 1958–1961

The largest famine of the 20th century, and almost certainly of all time, was the 1958–1961 famine associated with the Great Leap Forward in China. The immediate causes of this famine lay in Mao Zedong's ill-fated attempt to transform China from an agricultural nation to an industrial power in one huge leap. Communist Party cadres across China insisted that peasants abandon their farms for collective farms, and begin to produce steel in small foundries, often melting down their farm instruments in the process. Collectivisation undermined incentives for the investment of labor and resources in agriculture; unrealistic plans for decentralized metal production sapped needed labor; unfavorable weather conditions; and communal dining halls encouraged overconsumption of available food. Such was the centralized control of information and the intense pressure on party cadres to report only good news—such as production quotas met or exceeded—that information about the escalating disaster was effectively suppressed. When the leadership did become aware of the scale of the famine, it did little to respond, and continued to ban any discussion of the cataclysm. This blanket suppression of news was so effective that very few Chinese citizens were aware of the scale of the famine, and the greatest peacetime demographic disaster of the 20th century only became widely known twenty years later, when the veil of censorship began to lift.

The number of famine deaths during 1958–1961 range from 18 million to at least 42 million people, with a further 30 million cancelled or delayed births. Agricultural collectivisation policies began to be reversed in 1978.

Chinese Diaspora

Main articles: Overseas Chinese and Chinese emigration

Chinese emigration first occurred thousands of years ago. The mass emigration that occurred from the 19th century to 1949 was caused mainly by wars and starvation in mainland China, as well as political corruption. Most migrants were illiterate or poorly educated peasants, called by the now-recognized racial slur coolies (Chinese: 苦力, literally "hard labor"), who migrated to developing countries in need of labor, such as the Americas, Australia, South Africa, Southeast Asia, Malaya and other places.

In 2009, there were 40-45 million overseas Chinese. They lived in 180 countries; 75% lived in Southeast Asia, and 19% in the United States.

In 2011, there were 73.3% of overseas Chinese lived in 35 Asia countries, and 18.6 in 40 countries of the Americas.

One-Child policy

Main article: One-child policy

From 1980 to 2015, the government of China permitted the great majority of families to have only one child. The ongoing Cultural Revolution and the strain it placed on the nation were large factors. During this time, the birth rate dropped from nearly 6 children per woman to just under 3. (The colloquial term "births per woman" is usually formalized as the Total Fertility Rate (TFR), a technical term in demographic analysis meaning the average number of children that would be born to a woman over her lifetime if she were to experience the exact current age-specific fertility rates through her lifetime.)

As China's youngest generation (born under the one-child policy) came of age for formation of the next generation, a single child would be left with having to provide support for their two parents and four grandparents. By 2014 families could have two children if one of the parents is an only child.

The policy was supposedly voluntary. It was more strongly enforced in urban areas, where housing was in very short supply. Policies included free contraceptives, financial and employment incentives, economic penalties, and sometimes forced abortions and sterilizations.

Two-child policy

Main article: Two-child policy

After 2000 the policy was steadily relaxed. Han Chinese living in rural areas were often permitted to have two children, as exceptions existed if the first child was a daughter. Because of cases such as these, as well as urban couples who simply paid a fine (or "social maintenance fee") to have more children, the overall fertility rate of mainland China is, in fact, closer to two children per family than to one child per family (1.8). In addition, since 2012, Han Chinese in southern Xinjiang were allowed to have two children. This, along with incentives and restrictions against higher Muslim Uyghur fertility, was seen as attempt to counter the threat of Uyghur separatism.

In 2016 the national policy changed to a two-child policy; in 2018 it changed to a three-policy. The new policies helped address the aging issue in China.

In 2018, about two years after the new policy reform, China is facing new ramifications from the two-child policy. Since the revision of the one-child policy, 90 million women have become eligible to have a second child. According to The Economist, the new two-child policy may have negative implications on gender roles, with new expectations for women to bear more children and to abandon their careers.

After the reform, China saw a short-lived boost in fertility rate for 2016. Chinese women gave birth to 17.9 million babies in 2016 (a record value in the 21st century), but the number of births declined by 3.5% to 17.2 million in 2017, and to 15.2 million in 2018.

In China, men still have greater marital power, which increases fertility pressure on their female partners. The dynamic of relationships (amount of "power" held by each parent), and the amount of resources each parent has contributes to the struggle for dominance. Resources would be items such as income, and health insurance. Dominance would be described as who has the final say in pregnancy, who has to resign in their career for maternal/parental leave. However, women have shown interest in a second child if the first child did not possess the desired gender.

Chinese couples were also polled and stated that they would rather invest in one child opposed to two children. To add, another concern for couples would be the high costs of raising another child; China's childcare system needs to be further developed. The change in cultural norms appears to be having negative consequences and leads to fear of a large aging population with smaller younger generations; thus the lack of workforce to drive the economy.

In May 2018, it was reported that Chinese authorities were in the process of ending their population control policies. In May 2021, the Chinese government announced it would scrap the two child policy in favour of a three child policy, allowing couples to have three children in order to mitigate the country's falling birth rates.

Biosynthesis

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Biosynthesis 

Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.

The prerequisite elements for biosynthesis include: precursor compounds, chemical energy (e.g. ATP), and catalytic enzymes which may require coenzymes (e.g.NADH, NADPH). These elements create monomers, the building blocks for macromolecules. Some important biological macromolecules include: proteins, which are composed of amino acid monomers joined via peptide bonds, and DNA molecules, which are composed of nucleotides joined via phosphodiester bonds.

Properties of chemical reactions

Biosynthesis occurs due to a series of chemical reactions. For these reactions to take place, the following elements are necessary:

• Precursor compounds: these compounds are the starting molecules or substrates in a reaction. These may also be viewed as the reactants in a given chemical process.
• Chemical energy: chemical energy can be found in the form of high energy molecules. These molecules are required for energetically unfavorable reactions. Furthermore, the hydrolysis of these compounds drives a reaction forward. High energy molecules, such as ATP, have three phosphates. Often, the terminal phosphate is split off during hydrolysis and transferred to another molecule.
• Catalytic enzymes: these molecules are special proteins that catalyze a reaction by increasing the rate of the reaction and lowering the activation energy.
• Coenzymes or cofactors: cofactors are molecules that assist in chemical reactions. These may be metal ions, vitamin derivatives such as NADH and acetyl CoA, or non-vitamin derivatives such as ATP. In the case of NADH, the molecule transfers a hydrogen, whereas acetyl CoA transfers an acetyl group, and ATP transfers a phosphate.

In the simplest sense, the reactions that occur in biosynthesis have the following format:

${\displaystyle {\ce {Reactant ->[][enzyme] Product}}}$

Some variations of this basic equation which will be discussed later in more detail are:

1. Simple compounds which are converted into other compounds, usually as part of a multiple step reaction pathway. Two examples of this type of reaction occur during the formation of nucleic acids and the charging of tRNA prior to translation. For some of these steps, chemical energy is required:

   ${\displaystyle {\ce {{Precursor~molecule}+ATP<=>{product~AMP}+PP_{i}}}}$

2. Simple compounds that are converted into other compounds with the assistance of cofactors. For example, the synthesis of phospholipids requires acetyl CoA, while the synthesis of another membrane component, sphingolipids, requires NADH and FADH for the formation the sphingosine backbone. The general equation for these examples is:

   ${\displaystyle {\ce {{Precursor~molecule}+Cofactor->[][enzyme]macromolecule}}}$

3. Simple compounds that join to create a macromolecule. For example, fatty acids join to form phospholipids. In turn, phospholipids and cholesterol interact noncovalently in order to form the lipid bilayer. This reaction may be depicted as follows:

   ${\displaystyle {\ce {{Molecule~1}+Molecule~2->macromolecule}}}$

Lipid

Lipid membrane bilayer

Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. For example, the simplest structures of lipids are fatty acids. Fatty acids are hydrocarbon derivatives; they contain a carboxyl group "head" and a hydrocarbon chain "tail". These fatty acids create larger components, which in turn incorporate noncovalent interactions to form the lipid bilayer. Fatty acid chains are found in two major components of membrane lipids: phospholipids and sphingolipids. A third major membrane component, cholesterol, does not contain these fatty acid units.

Phospholipids

The foundation of all biomembranes consists of a bilayer structure of phospholipids. The phospholipid molecule is amphipathic; it contains a hydrophilic polar head and a hydrophobic nonpolar tail. The phospholipid heads interact with each other and aqueous media, while the hydrocarbon tails orient themselves in the center, away from water. These latter interactions drive the bilayer structure that acts as a barrier for ions and molecules.

There are various types of phospholipids; consequently, their synthesis pathways differ. However, the first step in phospholipid synthesis involves the formation of phosphatidate or diacylglycerol 3-phosphate at the endoplasmic reticulum and outer mitochondrial membrane. The synthesis pathway is found below:

The pathway starts with glycerol 3-phosphate, which gets converted to lysophosphatidate via the addition of a fatty acid chain provided by acyl coenzyme A. Then, lysophosphatidate is converted to phosphatidate via the addition of another fatty acid chain contributed by a second acyl CoA; all of these steps are catalyzed by the glycerol phosphate acyltransferase enzyme. Phospholipid synthesis continues in the endoplasmic reticulum, and the biosynthesis pathway diverges depending on the components of the particular phospholipid.

Sphingolipids

Like phospholipids, these fatty acid derivatives have a polar head and nonpolar tails. Unlike phospholipids, sphingolipids have a sphingosine backbone. Sphingolipids exist in eukaryotic cells and are particularly abundant in the central nervous system. For example, sphingomyelin is part of the myelin sheath of nerve fibers.

Sphingolipids are formed from ceramides that consist of a fatty acid chain attached to the amino group of a sphingosine backbone. These ceramides are synthesized from the acylation of sphingosine. The biosynthetic pathway for sphingosine is found below:

As the image denotes, during sphingosine synthesis, palmitoyl CoA and serine undergo a condensation reaction which results in the formation of dehydrosphingosine. This product is then reduced to form dihydrospingosine, which is converted to sphingosine via the oxidation reaction by FAD.

Cholesterol

This lipid belongs to a class of molecules called sterols. Sterols have four fused rings and a hydroxyl group. Cholesterol is a particularly important molecule. Not only does it serve as a component of lipid membranes, it is also a precursor to several steroid hormones, including cortisol, testosterone, and estrogen.

Cholesterol is synthesized from acetyl CoA. The pathway is shown below:

More generally, this synthesis occurs in three stages, with the first stage taking place in the cytoplasm and the second and third stages occurring in the endoplasmic reticulum. The stages are as follows:

1. The synthesis of isopentenyl pyrophosphate, the "building block" of cholesterol

2. The formation of squalene via the condensation of six molecules of isopentenyl phosphate

3. The conversion of squalene into cholesterol via several enzymatic reactions

Nucleotides

The biosynthesis of nucleotides involves enzyme-catalyzed reactions that convert substrates into more complex products. Nucleotides are the building blocks of DNA and RNA. Nucleotides are composed of a five-membered ring formed from ribose sugar in RNA, and deoxyribose sugar in DNA; these sugars are linked to a purine or pyrimidine base with a glycosidic bond and a phosphate group at the 5' location of the sugar.

Purine nucleotides

The synthesis of IMP.

The DNA nucleotides adenosine and guanosine consist of a purine base attached to a ribose sugar with a glycosidic bond. In the case of RNA nucleotides deoxyadenosine and deoxyguanosine, the purine bases are attached to a deoxyribose sugar with a glycosidic bond. The purine bases on DNA and RNA nucleotides are synthesized in a twelve-step reaction mechanism present in most single-celled organisms. Higher eukaryotes employ a similar reaction mechanism in ten reaction steps. Purine bases are synthesized by converting phosphoribosyl pyrophosphate (PRPP) to inosine monophosphate (IMP), which is the first key intermediate in purine base biosynthesis. Further enzymatic modification of IMP produces the adenosine and guanosine bases of nucleotides.

1. The first step in purine biosynthesis is a condensation reaction, performed by glutamine-PRPP amidotransferase. This enzyme transfers the amino group from glutamine to PRPP, forming 5-phosphoribosylamine. The following step requires the activation of glycine by the addition of a phosphate group from ATP.
2. GAR synthetase performs the condensation of activated glycine onto PRPP, forming glycineamide ribonucleotide (GAR).
3. GAR transformylase adds a formyl group onto the amino group of GAR, forming formylglycinamide ribonucleotide (FGAR).
4. FGAR amidotransferase catalyzes the addition of a nitrogen group to FGAR, forming formylglycinamidine ribonucleotide (FGAM).
5. FGAM cyclase catalyzes ring closure, which involves removal of a water molecule, forming the 5-membered imidazole ring 5-aminoimidazole ribonucleotide (AIR).
6. N5-CAIR synthetase transfers a carboxyl group, forming the intermediate N5-carboxyaminoimidazole ribonucleotide (N5-CAIR).
7. N5-CAIR mutase rearranges the carboxyl functional group and transfers it onto the imidazole ring, forming carboxyamino- imidazole ribonucleotide (CAIR). The two step mechanism of CAIR formation from AIR is mostly found in single celled organisms. Higher eukaryotes contain the enzyme AIR carboxylase, which transfers a carboxyl group directly to AIR imidazole ring, forming CAIR.
8. SAICAR synthetase forms a peptide bond between aspartate and the added carboxyl group of the imidazole ring, forming N-succinyl-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR).
9. SAICAR lyase removes the carbon skeleton of the added aspartate, leaving the amino group and forming 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR).
10. AICAR transformylase transfers a carbonyl group to AICAR, forming N-formylaminoimidazole- 4-carboxamide ribonucleotide (FAICAR).
11. The final step involves the enzyme IMP synthase, which performs the purine ring closure and forms the inosine monophosphate intermediate.

Pyrimidine nucleotides

Uridine monophosphate (UMP) biosynthesis

Other DNA and RNA nucleotide bases that are linked to the ribose sugar via a glycosidic bond are thymine, cytosine and uracil (which is only found in RNA). Uridine monophosphate biosynthesis involves an enzyme that is located in the mitochondrial inner membrane and multifunctional enzymes that are located in the cytosol.

1. The first step involves the enzyme carbamoyl phosphate synthase combining glutamine with CO₂ in an ATP dependent reaction to form carbamoyl phosphate.
2. Aspartate carbamoyltransferase condenses carbamoyl phosphate with aspartate to form uridosuccinate.
3. Dihydroorotase performs ring closure, a reaction that loses water, to form dihydroorotate.
4. Dihydroorotate dehydrogenase, located within the mitochondrial inner membrane, oxidizes dihydroorotate to orotate.
5. Orotate phosphoribosyl hydrolase (OMP pyrophosphorylase) condenses orotate with PRPP to form orotidine-5'-phosphate.
6. OMP decarboxylase catalyzes the conversion of orotidine-5'-phosphate to UMP.

After the uridine nucleotide base is synthesized, the other bases, cytosine and thymine are synthesized. Cytosine biosynthesis is a two-step reaction which involves the conversion of UMP to UTP. Phosphate addition to UMP is catalyzed by a kinase enzyme. The enzyme CTP synthase catalyzes the next reaction step: the conversion of UTP to CTP by transferring an amino group from glutamine to uridine; this forms the cytosine base of CTP. The mechanism, which depicts the reaction UTP + ATP + glutamine ⇔ CTP + ADP + glutamate, is below:

Cytosine is a nucleotide that is present in both DNA and RNA. However, uracil is only found in RNA. Therefore, after UTP is synthesized, it is must be converted into a deoxy form to be incorporated into DNA. This conversion involves the enzyme ribonucleoside triphosphate reductase. This reaction that removes the 2'-OH of the ribose sugar to generate deoxyribose is not affected by the bases attached to the sugar. This non-specificity allows ribonucleoside triphosphate reductase to convert all nucleotide triphosphates to deoxyribonucleotide by a similar mechanism.

In contrast to uracil, thymine bases are found mostly in DNA, not RNA. Cells do not normally contain thymine bases that are linked to ribose sugars in RNA, thus indicating that cells only synthesize deoxyribose-linked thymine. The enzyme thymidylate synthetase is responsible for synthesizing thymine residues from dUMP to dTMP. This reaction transfers a methyl group onto the uracil base of dUMP to generate dTMP. The thymidylate synthase reaction, dUMP + 5,10-methylenetetrahydrofolate ⇔ dTMP + dihydrofolate, is shown to the right.

DNA

As DNA polymerase moves in a 3' to 5' direction along the template strand, it synthesizes a new strand in the 5' to 3' direction

Although there are differences between eukaryotic and prokaryotic DNA synthesis, the following section denotes key characteristics of DNA replication shared by both organisms.

DNA is composed of nucleotides that are joined by phosphodiester bonds. DNA synthesis, which takes place in the nucleus, is a semiconservative process, which means that the resulting DNA molecule contains an original strand from the parent structure and a new strand. DNA synthesis is catalyzed by a family of DNA polymerases that require four deoxynucleoside triphosphates, a template strand, and a primer with a free 3'OH in which to incorporate nucleotides.

In order for DNA replication to occur, a replication fork is created by enzymes called helicases which unwind the DNA helix. Topoisomerases at the replication fork remove supercoils caused by DNA unwinding, and single-stranded DNA binding proteins maintain the two single-stranded DNA templates stabilized prior to replication.

DNA synthesis is initiated by the RNA polymerase primase, which makes an RNA primer with a free 3'OH. This primer is attached to the single-stranded DNA template, and DNA polymerase elongates the chain by incorporating nucleotides; DNA polymerase also proofreads the newly synthesized DNA strand.

During the polymerization reaction catalyzed by DNA polymerase, a nucleophilic attack occurs by the 3'OH of the growing chain on the innermost phosphorus atom of a deoxynucleoside triphosphate; this yields the formation of a phosphodiester bridge that attaches a new nucleotide and releases pyrophosphate.

Two types of strands are created simultaneously during replication: the leading strand, which is synthesized continuously and grows towards the replication fork, and the lagging strand, which is made discontinuously in Okazaki fragments and grows away from the replication fork. Okazaki fragments are covalently joined by DNA ligase to form a continuous strand. Then, to complete DNA replication, RNA primers are removed, and the resulting gaps are replaced with DNA and joined via DNA ligase.

Amino acids

Main article: Amino acid synthesis

A protein is a polymer that is composed from amino acids that are linked by peptide bonds. There are more than 300 amino acids found in nature of which only twenty, known as the standard amino acids, are the building blocks for protein. Only green plants and most microbes are able to synthesize all of the 20 standard amino acids that are needed by all living species. Mammals can only synthesize ten of the twenty standard amino acids. The other amino acids, valine, methionine, leucine, isoleucine, phenylalanine, lysine, threonine and tryptophan for adults and histidine, and arginine for babies are obtained through diet.

Amino acid basic structure

L-amino acid

The general structure of the standard amino acids includes a primary amino group, a carboxyl group and the functional group attached to the α-carbon. The different amino acids are identified by the functional group. As a result of the three different groups attached to the α-carbon, amino acids are asymmetrical molecules. For all standard amino acids, except glycine, the α-carbon is a chiral center. In the case of glycine, the α-carbon has two hydrogen atoms, thus adding symmetry to this molecule. With the exception of proline, all of the amino acids found in life have the L-isoform conformation. Proline has a functional group on the α-carbon that forms a ring with the amino group.

Nitrogen source

One major step in amino acid biosynthesis involves incorporating a nitrogen group onto the α-carbon. In cells, there are two major pathways of incorporating nitrogen groups. One pathway involves the enzyme glutamine oxoglutarate aminotransferase (GOGAT) which removes the amide amino group of glutamine and transfers it onto 2-oxoglutarate, producing two glutamate molecules. In this catalysis reaction, glutamine serves as the nitrogen source. An image illustrating this reaction is found to the right.

The other pathway for incorporating nitrogen onto the α-carbon of amino acids involves the enzyme glutamate dehydrogenase (GDH). GDH is able to transfer ammonia onto 2-oxoglutarate and form glutamate. Furthermore, the enzyme glutamine synthetase (GS) is able to transfer ammonia onto glutamate and synthesize glutamine, replenishing glutamine.

The glutamate family of amino acids

The glutamate family of amino acids includes the amino acids that derive from the amino acid glutamate. This family includes: glutamate, glutamine, proline, and arginine. This family also includes the amino acid lysine, which is derived from α-ketoglutarate.

The biosynthesis of glutamate and glutamine is a key step in the nitrogen assimilation discussed above. The enzymes GOGAT and GDH catalyze the nitrogen assimilation reactions.

In bacteria, the enzyme glutamate 5-kinase initiates the biosynthesis of proline by transferring a phosphate group from ATP onto glutamate. The next reaction is catalyzed by the enzyme pyrroline-5-carboxylate synthase (P5CS), which catalyzes the reduction of the ϒ-carboxyl group of L-glutamate 5-phosphate. This results in the formation of glutamate semialdehyde, which spontaneously cyclizes to pyrroline-5-carboxylate. Pyrroline-5-carboxylate is further reduced by the enzyme pyrroline-5-carboxylate reductase (P5CR) to yield a proline amino acid.

In the first step of arginine biosynthesis in bacteria, glutamate is acetylated by transferring the acetyl group from acetyl-CoA at the N-α position; this prevents spontaneous cyclization. The enzyme N-acetylglutamate synthase (glutamate N-acetyltransferase) is responsible for catalyzing the acetylation step. Subsequent steps are catalyzed by the enzymes N-acetylglutamate kinase, N-acetyl-gamma-glutamyl-phosphate reductase, and acetylornithine/succinyldiamino pimelate aminotransferase and yield the N-acetyl-L-ornithine. The acetyl group of acetylornithine is removed by the enzyme acetylornithinase (AO) or ornithine acetyltransferase (OAT), and this yields ornithine. Then, the enzymes citrulline and argininosuccinate convert ornithine to arginine.

The diaminopimelic acid pathway

There are two distinct lysine biosynthetic pathways: the diaminopimelic acid pathway and the α-aminoadipate pathway. The most common of the two synthetic pathways is the diaminopimelic acid pathway; it consists of several enzymatic reactions that add carbon groups to aspartate to yield lysine:

1. Aspartate kinase initiates the diaminopimelic acid pathway by phosphorylating aspartate and producing aspartyl phosphate.
2. Aspartate semialdehyde dehydrogenase catalyzes the NADPH-dependent reduction of aspartyl phosphate to yield aspartate semialdehyde.
3. 4-hydroxy-tetrahydrodipicolinate synthase adds a pyruvate group to the β-aspartyl-4-semialdehyde, and a water molecule is removed. This causes cyclization and gives rise to (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate.
4. 4-hydroxy-tetrahydrodipicolinate reductase catalyzes the reduction of (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate by NADPH to yield Δ'-piperideine-2,6-dicarboxylate (2,3,4,5-tetrahydrodipicolinate) and H₂O.
5. Tetrahydrodipicolinate acyltransferase catalyzes the acetylation reaction that results in ring opening and yields N-acetyl α-amino-ε-ketopimelate.
6. N-succinyl-α-amino-ε-ketopimelate-glutamate aminotransaminase catalyzes the transamination reaction that removes the keto group of N-acetyl α-amino-ε-ketopimelate and replaces it with an amino group to yield N-succinyl-L-diaminopimelate.
7. N-acyldiaminopimelate deacylase catalyzes the deacylation of N-succinyl-L-diaminopimelate to yield L,L-diaminopimelate.
8. DAP epimerase catalyzes the conversion of L,L-diaminopimelate to the meso form of L,L-diaminopimelate.
9. DAP decarboxylase catalyzes the removal of the carboxyl group, yielding L-lysine.

The serine family of amino acids

The serine family of amino acid includes: serine, cysteine, and glycine. Most microorganisms and plants obtain the sulfur for synthesizing methionine from the amino acid cysteine. Furthermore, the conversion of serine to glycine provides the carbons needed for the biosynthesis of the methionine and histidine.

During serine biosynthesis, the enzyme phosphoglycerate dehydrogenase catalyzes the initial reaction that oxidizes 3-phospho-D-glycerate to yield 3-phosphonooxypyruvate. The following reaction is catalyzed by the enzyme phosphoserine aminotransferase, which transfers an amino group from glutamate onto 3-phosphonooxypyruvate to yield L-phosphoserine. The final step is catalyzed by the enzyme phosphoserine phosphatase, which dephosphorylates L-phosphoserine to yield L-serine.

There are two known pathways for the biosynthesis of glycine. Organisms that use ethanol and acetate as the major carbon source utilize the glyconeogenic pathway to synthesize glycine. The other pathway of glycine biosynthesis is known as the glycolytic pathway. This pathway converts serine synthesized from the intermediates of glycolysis to glycine. In the glycolytic pathway, the enzyme serine hydroxymethyltransferase catalyzes the cleavage of serine to yield glycine and transfers the cleaved carbon group of serine onto tetrahydrofolate, forming 5,10-methylene-tetrahydrofolate.

Cysteine biosynthesis is a two-step reaction that involves the incorporation of inorganic sulfur. In microorganisms and plants, the enzyme serine acetyltransferase catalyzes the transfer of acetyl group from acetyl-CoA onto L-serine to yield O-acetyl-L-serine. The following reaction step, catalyzed by the enzyme O-acetyl serine (thiol) lyase, replaces the acetyl group of O-acetyl-L-serine with sulfide to yield cysteine.

The aspartate family of amino acids

The aspartate family of amino acids includes: threonine, lysine, methionine, isoleucine, and aspartate. Lysine and isoleucine are considered part of the aspartate family even though part of their carbon skeleton is derived from pyruvate. In the case of methionine, the methyl carbon is derived from serine and the sulfur group, but in most organisms, it is derived from cysteine.

The biosynthesis of aspartate is a one step reaction that is catalyzed by a single enzyme. The enzyme aspartate aminotransferase catalyzes the transfer of an amino group from aspartate onto α-ketoglutarate to yield glutamate and oxaloacetate. Asparagine is synthesized by an ATP-dependent addition of an amino group onto aspartate; asparagine synthetase catalyzes the addition of nitrogen from glutamine or soluble ammonia to aspartate to yield asparagine.

The diaminopimelic acid lysine biosynthetic pathway

The diaminopimelic acid biosynthetic pathway of lysine belongs to the aspartate family of amino acids. This pathway involves nine enzyme-catalyzed reactions that convert aspartate to lysine.

1. Aspartate kinase catalyzes the initial step in the diaminopimelic acid pathway by transferring a phosphoryl from ATP onto the carboxylate group of aspartate, which yields aspartyl-β-phosphate.
2. Aspartate-semialdehyde dehydrogenase catalyzes the reduction reaction by dephosphorylation of aspartyl-β-phosphate to yield aspartate-β-semialdehyde.
3. Dihydrodipicolinate synthase catalyzes the condensation reaction of aspartate-β-semialdehyde with pyruvate to yield dihydrodipicolinic acid.
4. 4-hydroxy-tetrahydrodipicolinate reductase catalyzes the reduction of dihydrodipicolinic acid to yield tetrahydrodipicolinic acid.
5. Tetrahydrodipicolinate N-succinyltransferase catalyzes the transfer of a succinyl group from succinyl-CoA on to tetrahydrodipicolinic acid to yield N-succinyl-L-2,6-diaminoheptanedioate.
6. N-succinyldiaminopimelate aminotransferase catalyzes the transfer of an amino group from glutamate onto N-succinyl-L-2,6-diaminoheptanedioate to yield N-succinyl-L,L-diaminopimelic acid.
7. Succinyl-diaminopimelate desuccinylase catalyzes the removal of acyl group from N-succinyl-L,L-diaminopimelic acid to yield L,L-diaminopimelic acid.
8. Diaminopimelate epimerase catalyzes the inversion of the α-carbon of L,L-diaminopimelic acid to yield meso-diaminopimelic acid.
9. Siaminopimelate decarboxylase catalyzes the final step in lysine biosynthesis that removes the carbon dioxide group from meso-diaminopimelic acid to yield L-lysine.

Proteins

The tRNA anticodon interacts with the mRNA codon in order to bind an amino acid to growing polypeptide chain.

 

The process of tRNA charging

Protein synthesis occurs via a process called translation. During translation, genetic material called mRNA is read by ribosomes to generate a protein polypeptide chain. This process requires transfer RNA (tRNA) which serves as an adaptor by binding amino acids on one end and interacting with mRNA at the other end; the latter pairing between the tRNA and mRNA ensures that the correct amino acid is added to the chain. Protein synthesis occurs in three phases: initiation, elongation, and termination. Prokaryotic (archaeal and bacterial) translation differs from eukaryotic translation; however, this section will mostly focus on the commonalities between the two organisms.

Additional background

Before translation can begin, the process of binding a specific amino acid to its corresponding tRNA must occur. This reaction, called tRNA charging, is catalyzed by aminoacyl tRNA synthetase. A specific tRNA synthetase is responsible for recognizing and charging a particular amino acid. Furthermore, this enzyme has special discriminator regions to ensure the correct binding between tRNA and its cognate amino acid. The first step for joining an amino acid to its corresponding tRNA is the formation of aminoacyl-AMP:

${\displaystyle {\ce {{Amino~acid}+ATP<=>{aminoacyl-AMP}+PP_{i}}}}$

This is followed by the transfer of the aminoacyl group from aminoacyl-AMP to a tRNA molecule. The resulting molecule is aminoacyl-tRNA:

${\displaystyle {\ce {{Aminoacyl-AMP}+ tRNA <=> {aminoacyl-tRNA}+ AMP}}}$

The combination of these two steps, both of which are catalyzed by aminoacyl tRNA synthetase, produces a charged tRNA that is ready to add amino acids to the growing polypeptide chain.

In addition to binding an amino acid, tRNA has a three nucleotide unit called an anticodon that base pairs with specific nucleotide triplets on the mRNA called codons; codons encode a specific amino acid. This interaction is possible thanks to the ribosome, which serves as the site for protein synthesis. The ribosome possesses three tRNA binding sites: the aminoacyl site (A site), the peptidyl site (P site), and the exit site (E site).

There are numerous codons within an mRNA transcript, and it is very common for an amino acid to be specified by more than one codon; this phenomenon is called degeneracy. In all, there are 64 codons, 61 of each code for one of the 20 amino acids, while the remaining codons specify chain termination.

Translation in steps

As previously mentioned, translation occurs in three phases: initiation, elongation, and termination.

Translation

Step 1: Initiation

The completion of the initiation phase is dependent on the following three events:

1. The recruitment of the ribosome to mRNA

2. The binding of a charged initiator tRNA into the P site of the ribosome

3. The proper alignment of the ribosome with mRNA's start codon

Step 2: Elongation

Following initiation, the polypeptide chain is extended via anticodon:codon interactions, with the ribosome adding amino acids to the polypeptide chain one at a time. The following steps must occur to ensure the correct addition of amino acids:

1. The binding of the correct tRNA into the A site of the ribosome

2. The formation of a peptide bond between the tRNA in the A site and the polypeptide chain attached to the tRNA in the P site

3. Translocation or advancement of the tRNA-mRNA complex by three nucleotides

Translocation "kicks off" the tRNA at the E site and shifts the tRNA from the A site into the P site, leaving the A site free for an incoming tRNA to add another amino acid.

Step 3: Termination

The last stage of translation occurs when a stop codon enters the A site. Then, the following steps occur:

1. The recognition of codons by release factors, which causes the hydrolysis of the polypeptide chain from the tRNA located in the P site

2. The release of the polypeptide chain

3. The dissociation and "recycling" of the ribosome for future translation processes

A summary table of the key players in translation is found below:

Key players in Translation	Translation Stage	Purpose
tRNA synthetase	before initiation	Responsible for tRNA charging
mRNA	initiation, elongation, termination	Template for protein synthesis; contains regions named codons which encode amino acids
tRNA	initiation, elongation, termination	Binds ribosomes sites A, P, E; anticodon base pairs with mRNA codon to ensure that the correct amino acid is incorporated into the growing polypeptide chain
ribosome	initiation, elongation, termination	Directs protein synthesis and catalyzes the formation of the peptide bond

Diseases associated with macromolecule deficiency

Familial hypercholesterolemia causes cholesterol deposits

Errors in biosynthetic pathways can have deleterious consequences including the malformation of macromolecules or the underproduction of functional molecules. Below are examples that illustrate the disruptions that occur due to these inefficiencies.

• Familial hypercholesterolemia: this disorder is characterized by the absence of functional receptors for LDL. Deficiencies in the formation of LDL receptors may cause faulty receptors which disrupt the endocytic pathway, inhibiting the entry of LDL into the liver and other cells. This causes a buildup of LDL in the blood plasma, which results in atherosclerotic plaques that narrow arteries and increase the risk of heart attacks.
• Lesch–Nyhan syndrome: this genetic disease is characterized by self- mutilation, mental deficiency, and gout. It is caused by the absence of hypoxanthine-guanine phosphoribosyltransferase, which is a necessary enzyme for purine nucleotide formation. The lack of enzyme reduces the level of necessary nucleotides and causes the accumulation of biosynthesis intermediates, which results in the aforementioned unusual behavior.
• Severe combined immunodeficiency (SCID): SCID is characterized by a loss of T cells. Shortage of these immune system components increases the susceptibility to infectious agents because the affected individuals cannot develop immunological memory. This immunological disorder results from a deficiency in adenosine deanimase activity, which causes a buildup of dATP. These dATP molecules then inhibit ribonucleotide reductase, which prevents of DNA synthesis.
• Huntington's disease: this neurological disease is caused from errors that occur during DNA synthesis. These errors or mutations lead to the expression of a mutant huntingtin protein, which contains repetitive glutamine residues that are encoded by expanding CAG trinucleotide repeats in the gene. Huntington's disease is characterized by neuronal loss and gliosis. Symptoms of the disease include: movement disorder, cognitive decline, and behavioral disorder.