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8.5:

์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ

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The Citric Acid Cycle

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– [๊ฐ•์‚ฌ] ๊ตฌ์—ฐ์‚ฐ ์ˆœํ™˜์€๋ฏธํ† ์ฝ˜๋“œ๋ฆฌ์•„ ๊ธฐ์งˆ์—์„œ ์ผ์–ด๋‚˜๋Š”๋ฐ˜์‘์˜ ํ ๋ฃจํ”„์ž…๋‹ˆ๋‹ค.์‚ฐํ™” ํ™˜์›, ํƒˆ์ˆ˜, ์ˆ˜ํ™”๋ฐ ํƒˆ ์นด๋ฅด ๋ณต ์‹คํ™” ๋ฐ˜์‘ ํฌํ•จ.๊ทธ๊ฒƒ์˜ ์ด๋ฆ„์€ ์ค‘๊ฐ„ ํ™”ํ•ฉ๋ฌผ,๊ตฌ์—ฐ์‚ฐ์—์„œ ํŒŒ์ƒ๋œ๋‹ค.์ด ๋‹จ๊ณ„๊ฐ€ ํ•œ์Šค ํฌ๋ ™์Šค์— ์˜ํ•ด ์ฒ˜์Œ์œผ๋กœ ๊ธฐ์ˆ  ๋˜์—ˆ๊ธฐ๋•Œ๋ฌธ์—์ด ํ˜ธ๊ธฐ์„ฑ ๊ฒฝ๋กœ๋Š” ๋˜ํ•œ ํฌ๋ ™์Šค์ฃผ๊ธฐ๋กœ๋„ ์•Œ๋ ค์ ธ ์žˆ์Šต๋‹ˆ๋‹ค.ํฌ๋„๋‹น ๋Œ€์‚ฌ์—์žˆ์–ด ์ผ๋ จ์˜8 ๊ฐ€์ง€ ํšจ์†Œ ๋‹จ๊ณ„๊ฐ€ ์ค‘์š”ํ•ฉ๋‹ˆ๋‹ค.์‹œ์ž‘ํ•˜๊ธฐ ์œ„ํ•ด, ํ”ผ๋ฃจ ๋ฒ ์ดํŠธ์‚ฐํ™”๋กœ๋ถ€ํ„ฐ ์ƒ์„ฑ ๋œ ํ™”ํ•ฉ๋ฌผ ์ธ acetyl-CoA๋Š”4 ๊ฐœ์˜ ํƒ„์†Œ ๋ถ„์ž ์ธ ์˜ฅ์‚ด ์•„์„ธํ…Œ์ดํŠธ์— ์•„์„ธํ‹ธ๊ธฐ๋ฅผ ๊ณต๊ธ‰ํ•˜์—ฌ6 ํƒ„์†Œ ์ค‘๊ฐ„์ฒด ์ธ ๊ตฌ์—ฐ์‚ฐ์—ผ์„ ํ˜•์„ฑํ•ฉ๋‹ˆ๋‹ค.CoA ๊ทธ๋ฃน์€ ํ™ฉ์‚ฐ์—ผ ๊ทธ๋ฃน์— ๊ฒฐํ•ฉ๋˜์–ด๊ฒฐ๊ตญ ๋‹ค๋ฅธ ์•„์„ธํ‹ธ ๊ทธ๋ฃน๊ณผ๊ฒฐํ•ฉํ•˜๊ธฐ ์œ„ํ•ด ํ™•์‚ฐ๋ฉ๋‹ˆ๋‹ค.๊ทธ๋Ÿฐ ๋‹ค์Œ ๋ฌผ ๋ถ„์ž๋ฅผ ์ œ๊ฑฐํ•˜๊ณ  ๋Œ€์ฒดํ•˜์—ฌ๊ตฌ์—ฐ์‚ฐ์—ผ์„ ์ด์„ฑ์งˆ์ฒด ์ธ ์ด์†Œ ์‹œํŠธ๋ฅด์‚ฐ์œผ๋กœ ์ „ํ™˜์‹œํ‚ต๋‹ˆ๋‹ค.๊ทธ๋Ÿฐ ๋‹ค์Œ ๋ถ„์ž๋Š” ์‚ฐํ™”๋˜์–ดNAD +์™€ NADH ๋ฐ H +์™€ ์ด์‚ฐํ™”ํƒ„์†Œ๋ถ„์ž๋ฅผ ๊ฐ์†Œ์‹œํ‚ต๋‹ˆ๋‹ค.5 ํƒ„์†Œ ์•ŒํŒŒ ์ผ€ํ†  ๊ธ€๋ฃจ ํƒ€ ๋ ˆ์ดํŠธ ํ˜•์„ฑ.์ด ์ œํ’ˆ์€ ๋˜ ๋‹ค๋ฅธ ์ด์‚ฐํ™”ํƒ„์†Œ๋ถ„์ž์™€ ๋‘ ๊ฐœ์˜ ์ „์ž๋ฅผ ๋ฐฉ์ถœํ•˜์—ฌ ๋˜ ๋‹ค๋ฅธ NADํ”Œ๋Ÿฌ์Šค๋ฅผ NADH์™€ ์–‘์„ฑ์ž๋กœ ๊ฐ์†Œ ์‹œํ‚ค๋ฉฐ, ์ฝ”์—”์ž์ž„ A๊ฐ€๋ถ€์ฐฉ๋˜๋Š” ๋ถˆ์•ˆ์ •ํ•œ ๊ฒฐํ•ฉ์œผ๋กœ ๋ถ„์ž๋ฅผ ๋‚จ๊ธด๋‹ค.์„์‹œ ๋‹ CoA ํ˜•์„ฑ.๋‹ค์Œ ๋‹จ๊ณ„์—์„œ ๋ณดํšจ์†Œ๋Š”์ธ์‚ฐ์—ผ ๊ทธ๋ฃน์œผ๋กœ ๋Œ€์ฒด๋ฉ๋‹ˆ๋‹ค.๊ทธ๋Ÿฐ ๋‹ค์Œ ์ธ์‚ฐ์—ผ์ด GTP๋กœ ์˜ฎ๊ฒจ์ ธ ์ˆ™์‹ ์‚ฐ ์—ผ๊ณผGTP๊ฐ€ ์ƒ์„ฑ๋ฉ๋‹ˆ๋‹ค.ATP๋ฅผ ์ƒ์„ฑํ•˜๋Š” ๋ฐ ์‚ฌ์šฉํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค.6 ๋‹จ๊ณ„ ๋™์•ˆ ์ˆ™์‹œ ๋„ค์ดํŠธ๊ฐ€ ์‚ฐํ™”๋ฉ๋‹ˆ๋‹ค.์ˆ˜์†Œ ์›์ž๋กœ๋ถ€ํ„ฐ์˜ 2 ๊ฐœ์˜ ์ „์ž๊ฐ€์ „์ž ์บ๋ฆฌ์–ด ํ”Œ๋ผ ๋นˆ ์•„๋ฐ๋‹Œ ๋”” ๋‰ดํด๋ ˆ์˜คํ‹ฐ๋“œ FAD๋กœ๋ณ€ํ™˜๋˜์–ด FADH 2์™€ ํ‘ธ๋งˆ ๋ ˆ์ดํŠธ๋ฅผ ์ƒ์„ฑํ•œ๋‹ค.๊ทธ ๋‹ค์Œ ๋ฌผ์€ ์ƒ์„ฑ ๋œ ๋ถ„์ž์— ์ฒจ๊ฐ€๋˜๊ณ ๊ฒฐํ•ฉ ์žฌ๋ฐฐ์น˜ ํ›„์— ๋ง์‚ฐ์—ผ์œผ๋กœ ํ˜•์„ฑ๋ฉ๋‹ˆ๋‹ค.๋งˆ์ง€๋ง‰์œผ๋กœ,์ด ๋ถ„์ž๋Š” ์‚ฐํ™”๋˜์–ดNAD +๋ฅผ NADH ๋ฐ H +๋กœ ํ™˜์›์‹œ์ผœ ์›๋ž˜์˜ํ™”ํ•ฉ๋ฌผ ์ธ ์˜ฅ ์‚ด๋กœ ์•„์„ธํ…Œ์ดํŠธ๋ฅผ ์žฌ์ƒํ•ฉ๋‹ˆ๋‹ค.๊ฒฐ๊ตญ, ๊ฐ ์‚ฌ์ดํด์€ 3 ๊ฐœ์˜ NADH์™€1 ๊ฐœ์˜ FADH๋ฅผ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค.์ „์ž ์ˆ˜์†ก ์ฒด์ธ์— ์‚ฌ์šฉ๋˜๋Š”๊ณ  ์—๋„ˆ์ง€ ์ „์ž ์บ๋ฆฌ์–ด.

8.5:

์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ

ํฌ๋ ™์ŠคํšŒ๋กœ(Krebs cycle), TCA ํšŒ๋กœ(tricarboxylic acid cycle, ์ค„์—ฌ์„œ TCA cycle), ๊ตฌ์—ฐ์‚ฐํšŒ๋กœ๋ผ๊ณ ๋„ ์•Œ๋ ค์ ธ ์žˆ๋Š” ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ(citric acid cycle)๋Š” ์•„๋ฐ๋…ธ์‹ ์‚ผ์ธ์‚ฐ(ATP) ๋ถ„์ž 1๊ฐœ, NADH ๋ถ„์ž 3๊ฐœ, FADH2 ๋ถ„์ž 1๊ฐœ, CO2 ๋ถ„์ž 2๊ฐœ๋ฅผ ์ƒ์„ฑํ•˜๋Š” ๋ช‡ ๊ฐœ์˜ ์—๋„ˆ์ง€ ์ƒ์„ฑ ๋ฐ˜์‘์œผ๋กœ ๊ตฌ์„ฑ๋˜์–ด ์žˆ์Šต๋‹ˆ๋‹ค.

์•„์„ธํ‹ธ CoA(acetyl CoA)๋Š” ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ๋กœ ๋“ค์–ด๊ฐ€๋Š” ์ง€์ ์ž…๋‹ˆ๋‹ค. ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ๋Š” ์ง„ํ•ต์„ธํฌ(eukaryotic cell)์˜ ๋ฏธํ† ์ฝ˜๋“œ๋ฆฌ์•„ ๋‚ด๋ง‰(์ฆ‰, ๊ธฐ์งˆ(matrix))์ด๋‚˜ ์›ํ•ต์„ธํฌ(prokaryotic cell)์˜ ์„ธํฌ์งˆ(cytoplasm)์—์„œ ๋ฐœ์ƒํ•ฉ๋‹ˆ๋‹ค. ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ ์ด์ „์— ํ”ผ๋ฃจ๋ธŒ์‚ฐ ์‚ฐํ™”(pyruvate oxidation)์—์„œ ํฌ๋„๋‹น ๋ถ„์ž 1๊ฐœ๋‹น ์•„์„ธํ‹ธ CoA ๋ถ„์ž 2๊ฐœ๊ฐ€ ์ƒ์„ฑ๋๊ธฐ ๋•Œ๋ฌธ์—, ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ๋Š” ํฌ๋„๋‹น ๋ถ„์ž 1๊ฐœ๋‹น ๋‘ ๋ฒˆ ์‹คํ–‰๋ฉ๋‹ˆ๋‹ค.

์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ๋Š” 8๋‹จ๊ณ„๋กœ ๋‚˜๋‰˜๊ณ  ๊ฐ ๋‹จ๊ณ„๋Š” ์„œ๋กœ ๋‹ค๋ฅธ ๋ถ„์ž๋ฅผ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค (์ดํ•˜ ์ƒ์„ฑ๋ฌผ์€ ์ดํƒค๋ฆญ์ฒด๋กœ ํ‘œ์‹œ๋ฉ๋‹ˆ๋‹ค).

ํšจ์†Œ์˜ ์ด‰๋งค ์ž‘์šฉ์œผ๋กœ ์•„์„ธํ‹ธ CoA(2ํƒ„์†Œ) 1๊ฐœ๋Š” ์˜ฅ์‚ด๋กœ์•„์„ธํŠธ์‚ฐ(oxaloacetic acid; 4ํƒ„์†Œ) 1๊ฐœ์™€ ๋ฐ˜์‘ํ•˜์—ฌ 6ํƒ„์†Œ ๋ถ„์ž์ธ ์‹œํŠธ๋ฅด์‚ฐ(citrate; ๊ตฌ์—ฐ์‚ฐ)์„ ํ˜•์„ฑํ•ฉ๋‹ˆ๋‹ค.

์ด ๋‹ค์Œ ์‹œํŠธ๋ฅด์‚ฐ์€ ๋ฌผ์„ ์ œ๊ฑฐํ•˜๊ณ  ์ถ”๊ฐ€ํ•˜๋Š” 2๋‹จ๊ณ„ ๊ณผ์ •์„ ํ†ตํ•ด ์ด์„ฑ์งˆ์ฒด(isomer) ์ค‘ ํ•˜๋‚˜์ธ ์•„์ด์†Œ์‹œํŠธ๋ฅด์‚ฐ(isocitrate; ์•„์ด์†Œ๊ตฌ์—ฐ์‚ฐ)์œผ๋กœ ๋ณ€ํ™˜๋ฉ๋‹ˆ๋‹ค.

์„ธ ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ๋Š” ์•„์ด์†Œ์‹œํŠธ๋ฅด์‚ฐ์ด ์‚ฐํ™”ํ•˜์—ฌ ์•ŒํŒŒ-์ผ€ํ† ๊ธ€๋ฃจํƒ€๋ฅด์‚ฐ(α-ketoglutarate; 5ํƒ„์†Œ)์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค. ์ด ๊ณผ์ •์€ CO2๋ฅผ ๋ฐฉ์ถœํ•˜๊ณ  NAD+๋ฅผ NADH๋กœ ํ™˜์›(reduction)ํ•ฉ๋‹ˆ๋‹ค.

๋„ค ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ๋Š” ์•ŒํŒŒ-์ผ€ํ† ๊ธ€๋ฃจํƒ€๋ฅด์‚ฐ์—์„œ ๋ถˆ์•ˆ์ •ํ•œ ํ™”ํ•ฉ๋ฌผ์ธ ์„์‹œ๋‹ CoA(succinyl CoA; ์‚ญ์‹œ๋‹ CoA; ์ˆ™์‹œ๋‹ CoA)๋ฅผ ํ˜•์„ฑํ•˜๋Š”๋ฐ, ์—ฌ๊ธฐ์„œ๋„ CO2๋ฅผ ๋ฐฉ์ถœํ•˜๊ณ  NAD+๋ฅผ NADH๋กœ ํ™˜์›ํ•ฉ๋‹ˆ๋‹ค.

๋‹ค์„ฏ ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ๋Š” ์ธ์‚ฐ๊ธฐ(phosphate group)๊ฐ€ ์„์‹œ๋‹ CoA์˜ CoA๊ธฐ(CoA group)๋ฅผ ๋Œ€์ฒดํ•ด ์„์‹ ์‚ฐ(succinate; ์ˆ™์‹ ์‚ฐ; ํ˜ธ๋ฐ•์‚ฐ; 4ํƒ„์†Œ)์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์ด ์ธ์‚ฐ๊ธฐ๋Š” ์•„๋ฐ๋…ธ์‹ ์ด์ธ์‚ฐ(ADP) ๋˜๋Š” ๊ตฌ์•„๋…ธ์‹ ์ด์ธ์‚ฐ(GDP)์— ์ „๋‹ฌ๋˜์–ด ์•„๋ฐ๋…ธ์‹ ์‚ผ์ธ์‚ฐ(ATP) ๋˜๋Š” ๊ตฌ์•„๋…ธ์‹ ์‚ผ์ธ์‚ฐ(GTP)์„ ํ˜•์„ฑํ•ฉ๋‹ˆ๋‹ค.

์—ฌ์„ฏ ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ๋Š” ์„์‹ ์‚ฐ์ด ์‚ฐํ™”ํ•˜์—ฌ ํ‘ธ๋งˆ๋ฅด์‚ฐ(fumarate; 4ํƒ„์†Œ)์„ ํ˜•์„ฑํ•ฉ๋‹ˆ๋‹ค. ์ด ๋ฐ˜์‘์€ FAD๋ฅผ FADH2๋กœ ํ™˜์›ํ•ฉ๋‹ˆ๋‹ค.

์ผ๊ณฑ ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ๋Š” ํ‘ธ๋งˆ๋ฅด์‚ฐ์— ๋ฌผ์ด ๋”ํ•ด์ ธ ๋ง์‚ฐ(malate; ์‚ฌ๊ณผ์‚ฐ; 4ํƒ„์†Œ)์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค.

๋งˆ์ง€๋ง‰ ๋‹จ๊ณ„์—์„œ๋Š” ๋ง์‚ฐ์ด ์‚ฐํ™”ํ•ด ์ฒซ ๋ฒˆ์งธ ๋‹จ๊ณ„์—์„œ ์•„์„ธํ‹ธ CoA์™€ ๋ฐ˜์‘ํ•˜๋Š” ํ™”ํ•ฉ๋ฌผ์ธ ์˜ฅ์‚ด๋กœ์•„์„ธํŠธ์‚ฐ(oxaloacetate)์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค. ์ด ๊ณผ์ •์—์„œ NAD+๋Š” NADH๋กœ ํ™˜์›๋ฉ๋‹ˆ๋‹ค.

์ด๋ ‡๊ฒŒ ์‹œํŠธ๋ฅด์‚ฐํšŒ๋กœ์—์„œ ์ƒ์„ฑ๋œ NADH์™€ FADH2๋Š” ์ „์ž์ „๋‹ฌ๊ณ„(electron transport chain)์— ์ „์ž๋ฅผ ๊ณต๊ธ‰ํ•ด ์ถ”๊ฐ€ ATP ์ƒ์„ฑ์„ ๋•์Šต๋‹ˆ๋‹ค.

Suggested Reading

Anderson, Nicole M., Patrick Mucka, Joseph G. Kern, and Hui Feng. “The Emerging Role and Targetability of the TCA Cycle in Cancer Metabolism.” Protein & Cell 9, no. 2 (February 2018): 216–37. [Source]