Editing Human brain (section)

===Metabolism===
[[File:PET-image.jpg|thumb|upright|alt=A flat oval object is surrounded by blue. The object is largely green-yellow, but contains a dark red patch at one end and a number of blue patches. |[[Positron emission tomography|PET]] image of the human brain showing energy consumption]]

The brain consumes up to 20% of the energy used by the human body, more than any other organ.<ref name="power-sciam">{{cite web |last=Swaminathan |first=N |title=Why Does the Brain Need So Much Power? |url=http://www.scientificamerican.com/article/why-does-the-brain-need-s/ |work=[[Scientific American]] |access-date=November 19, 2010 |date=April 29, 2008 |url-status=live |archive-url=https://web.archive.org/web/20140127171142/http://www.scientificamerican.com/article/why-does-the-brain-need-s/ |archive-date=January 27, 2014  }}</ref> In humans, [[blood glucose]] is the primary [[food energy|source of energy]] for most cells and is critical for normal function in a number of tissues, including the brain.<ref name="Glucose-Glycogen storage review" /> The human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals.<ref name="Glucose-Glycogen storage review">{{cite journal | vauthors = Wasserman DH | title = Four grams of glucose | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 296 | issue = 1 | pages = E11–21 | date = January 2009 | pmid = 18840763 | pmc = 2636990 | doi = 10.1152/ajpendo.90563.2008 | quote = Four grams of glucose circulates in the blood of a person weighing 70&nbsp;kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4&nbsp;g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated.&nbsp;... The brain consumes ~60% of the blood glucose used in the sedentary, fasted person.&nbsp;... The amount of glucose in the blood is preserved at the expense of glycogen reservoirs (Fig. 2). In postabsorptive humans, there are ~100&nbsp;g of glycogen in the liver and ~400&nbsp;g of glycogen in muscle. Carbohydrate oxidation by the working muscle can go up by ~10-fold with exercise, and yet after 1&nbsp;h, blood glucose is maintained at ~4&nbsp;g.&nbsp;... It is now well established that both insulin and exercise cause translocation of GLUT4 to the plasma membrane. Except for the fundamental process of GLUT4 translocation, [muscle glucose uptake (MGU)] is controlled differently with exercise and insulin. Contraction-stimulated intracellular signaling (52, 80) and MGU (34, 75, 77, 88, 91, 98) are insulin independent. Moreover, the fate of glucose extracted from the blood is different in response to exercise and insulin (91, 105). For these reasons, barriers to glucose flux from blood to muscle must be defined independently for these two controllers of MGU.}}</ref> Brain [[metabolism]] normally relies upon blood [[glucose]] as an energy source, but during times of low glucose (such as [[fasting]], [[endurance exercise]], or limited [[carbohydrate]] intake), the brain uses [[ketone bodies]] for fuel with a smaller need for glucose. The brain can also utilize [[Lactic acid#Exercise and lactate|lactate during exercise]].<ref>{{cite journal |title=Lactate fuels the human brain during exercise |last1=Quistorff |first1=B |last2=Secher |first2=N |last3=Van Lieshout |first3=J |date=July 24, 2008 |journal=[[The FASEB Journal]] |doi=10.1096/fj.08-106104 |pmid=18653766 |volume=22 |issue=10 |pages=3443–3449 |doi-access=free |s2cid=15394163 }}</ref> The brain stores glucose in the form of [[glycogen]], albeit in significantly smaller amounts than that found in the [[liver]] or [[skeletal muscle]].<ref>{{cite journal |last=Obel |first=L.F. |author2=Müller, M.S. |author3=Walls, A.B. |author4=Sickmann, H.M. |author5=Bak, L.K. |author6=Waagepetersen, H.S. |author7= Schousboe, A. |title=Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. |journal=Frontiers in Neuroenergetics |date=2012 |volume=4 |page=3 |pmid=22403540 |doi=10.3389/fnene.2012.00003 |pmc=3291878|doi-access=free }}</ref> [[Fatty acid#Length of free fatty acid chains|Long-chain fatty acid]]s cannot cross the [[blood–brain barrier]], but the liver can break these down to produce ketone bodies. However, [[short-chain fatty acid]]s (e.g., [[butyric acid]], [[propionic acid]], and [[acetic acid]]) and the [[Fatty acid#Length of free fatty acid chains|medium-chain fatty acids]], [[octanoic acid]] and [[heptanoic acid]], can cross the blood–brain barrier and be metabolised by [[brain cell]]s.<ref>{{cite journal |last1=Marin-Valencia |first1=I. |display-authors=etal |title=Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. |journal=Journal of Cerebral Blood Flow and Metabolism |date=February 2013 |volume=33 |issue=2 |pages=175–82 |pmid=23072752 |doi=10.1038/jcbfm.2012.151 |pmc=3564188}}</ref><ref name="SCFA MCT-mediated BBB passage - 2005 review">{{cite journal | author=Tsuji, A. | title=Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems | journal=NeuroRx | volume=2 | issue=1 | pages=54–62 | year=2005 | pmid=15717057 | pmc=539320 | doi=10.1602/neurorx.2.1.54 | quote=Uptake of valproic acid was reduced in the presence of medium-chain fatty acids such as hexanoate, octanoate, and decanoate, but not propionate or butyrate, indicating that valproic acid is taken up into the brain via a transport system for medium-chain fatty acids, not short-chain fatty acids.&nbsp;... Based on these reports, valproic acid is thought to be transported bidirectionally between blood and brain across the BBB via two distinct mechanisms, monocarboxylic acid-sensitive and medium-chain fatty acid-sensitive transporters, for efflux and uptake, respectively.}}</ref><ref name="SCFA MCT-mediated BBB passage - 2014 review">{{cite journal | last1=Vijay |first1=N. |last2=Morris |first2=M.E. | title=Role of monocarboxylate transporters in drug delivery to the brain | journal=Curr. Pharm. Des. | volume=20 | issue=10 | pages=1487–98 | year=2014 | pmid=23789956 | pmc=4084603 | doi=10.2174/13816128113199990462 | quote=Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate.&nbsp;... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as acetate and formate which are then metabolized in the astrocytes [78].}}</ref>

Although the human brain represents only 2% of the body weight, it receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body [[glucose]] utilization.<ref>{{cite book |last=Clark |first=D.D. |author2=Sokoloff. L. |editor1=Siegel, G.J.|editor2=Agranoff, B.W.|editor3=Albers, R.W.|editor4=Fisher, S.K.|editor5=Uhler, M.D. |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |publisher=Lippincott |location=Philadelphia |year=1999 |pages=637–670 |isbn=978-0-397-51820-3}}</ref> The brain mostly uses glucose for energy, and deprivation of glucose, as can happen in [[hypoglycemia]], can result in loss of consciousness.<ref name="Mrsulja">{{cite book |author=Mrsulja, B.B. |title=Pathophysiology of Cerebral Energy Metabolism |isbn=978-1-4684-3348-7 |publisher=[[Springer Science & Business Media]] |year=2012 |pages=2–3 |url=https://books.google.com/books?id=8yzvBwAAQBAJ&pg=PA2}}</ref> The energy consumption of the brain does not vary greatly over time, but active regions of the cortex consume somewhat more energy than inactive regions, which forms the basis for the [[functional neuroimaging]] methods of [[Positron emission tomography|PET]] and [[fMRI]].<ref>{{cite journal |last1=Raichle |first1=M. |year=2002 |title=Appraising the brain's energy budget |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |pages=10237–10239 |doi=10.1073/pnas.172399499 |pmid=12149485 |last2=Gusnard |first2=DA |pmc=124895 |issue=16|bibcode=2002PNAS...9910237R |doi-access=free }}</ref> These techniques provide a three-dimensional image of metabolic activity.<ref name="Steptoe">{{cite book |editor-last=Steptoe |editor-first=A. |last1=Gianaros |first1=Peter J. |last2=Gray |first2=Marcus A. |last3=Onyewuenyi |first3=Ikechukwu |last4=Critchley |first4=Hugo D.|title=Handbook of Behavioral Medicine |chapter=Neuroimaging Methods in Behavioral Medicine |isbn=978-0-387-09488-5 |publisher=[[Springer Science & Business Media]] |year=2010 |page=770 |chapter-url=https://books.google.com/books?id=Si9TtI5AGIEC&pg=PA770 |doi=10.1007/978-0-387-09488-5_50}}</ref> A preliminary study showed that brain metabolic requirements in humans peak at about five years old.<ref>{{Cite journal|last1=Kuzawa|first1=C. W.|last2=Chugani|first2=H. T.|last3=Grossman|first3=L. I.|last4=Lipovich|first4=L.|last5=Muzik|first5=O.|last6=Hof|first6=P. R.|last7=Wildman|first7=D. E.|last8=Sherwood|first8=C. C.|last9=Leonard|first9=W. R.|last10=Lange|first10=N.|date=2014-09-09|title=Metabolic costs and evolutionary implications of human brain development|journal=Proceedings of the National Academy of Sciences|volume=111|issue=36|pages=13010–13015|doi=10.1073/pnas.1323099111|issn=0027-8424|pmc=4246958|pmid=25157149|bibcode=2014PNAS..11113010K|doi-access=free}}</ref>

The function of [[sleep]] is not fully understood; however, there is evidence that sleep enhances the clearance of metabolic waste products, some of which are potentially [[neurotoxic]], from the brain and may also permit repair.<ref name="Glymphatic system and brain waste clearance 2017 review" /><ref>{{cite web |title=Brain may flush out toxins during sleep |url=http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_brain_sleep_10182013.htm |work=[[National Institutes of Health]] |access-date=October 25, 2013 |url-status=live |archive-url=https://web.archive.org/web/20131020220815/http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_brain_sleep_10182013.htm |archive-date=October 20, 2013  }}</ref><ref name="Sleep – clearance of neurotoxic waste products">{{cite journal | vauthors = Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M | title = Sleep drives metabolite clearance from the adult brain | journal = Science | volume = 342 | issue = 6156 | pages = 373–377 | date = October 2013 | pmid = 24136970 | pmc = 3880190 | doi = 10.1126/science.1241224 | quote = Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.| bibcode = 2013Sci...342..373X }}</ref> Evidence suggests that the increased clearance of metabolic waste during sleep occurs via increased functioning of the [[glymphatic system]].<ref name="Glymphatic system and brain waste clearance 2017 review">{{cite journal | vauthors = Bacyinski A, Xu M, Wang W, Hu J | title = The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy | journal = Frontiers in Neuroanatomy | volume = 11 | page = 101 | date = November 2017 | pmid = 29163074 | pmc = 5681909 | doi = 10.3389/fnana.2017.00101 | quote = The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. &nbsp;... In addition to Aβ clearance, the glymphatic system may be involved in the removal of other interstitial solutes and metabolites. By measuring the lactate concentration in the brains and cervical lymph nodes of awake and sleeping mice, Lundgaard et al. (2017) demonstrated that lactate can exit the CNS via the paravascular pathway. Their analysis took advantage of the substantiated hypothesis that glymphatic function is promoted during sleep (Xie et al., 2013; Lee et al., 2015; Liu et al., 2017).| doi-access = free }}</ref> Sleep may also have an effect on cognitive function by weakening unnecessary connections.<ref>{{cite journal |url=https://pdfs.semanticscholar.org/6f9d/f7817534e55865bd1f6b7da6d2912bdbeaf3.pdf |archive-url=https://web.archive.org/web/20181226232857/https://pdfs.semanticscholar.org/6f9d/f7817534e55865bd1f6b7da6d2912bdbeaf3.pdf |url-status=dead |archive-date=2018-12-26 |last1=Tononi |first1=Guilio |last2=Cirelli |first2=Chiara |title=Perchance to Prune |journal=Scientific American |volume=309 |issue=2 |date=August 2013 |pages=34–39 |pmid=23923204|doi=10.1038/scientificamerican0813-34 |bibcode=2013SciAm.309b..34T |s2cid=54052089 }}</ref>