pinghang～熱血白袍～

今天就來討論所謂的Kreb cycle 的重要性好了，在討論這個之前，你必須先了解這個反應是在粒線體內進行，雖然在這個循環中並沒有看到氧氣直接參與，但是要知道的是

今天要是沒有氧氣的存在（anaerobically），這個反應是不會進行的，因為會有一堆的 NADH, FADH2累積在粒腺體而反抑制這個循環的發生。

而也必須會去複習糖解作用（glycolyisis）的終產物 pyruvate在有氧的狀況下會進入粒線體往acetyl-CoA的方向-->TCA cycle

ＴＣＡcycle主要的功能是把 acetyl-CoA氧化成CO2,中間釋放的能量會由NADH, FADH2,GTP來儲存。

總反應式：Acetyl-CoA+3NAD+FAD+GDP+Pi-->2CO2+3NADH+FADH2+GTP

可以注意到中間的產物完全沒有出現在靜產物和靜反應物中

由此可知這個反應acetyl-CoA的唯一產物和命運及為氧化為CO2而非產生葡萄糖。

由glucose, fatty acids, ketone bodies, ketogenic amino acids, alcohol皆可經由氧化而產生acetyl-CoA而進入此cycle

此反應不受任何荷爾蒙的控制，也不受進食和空腹的影響。反而是細胞的能量狀態能控制此反應。

Cycle 重點：

1. Isocitrate dehydrogenase, major control enzyme is inhibited by NADH, ATP and activated by ADP

2. alfa-ketoglutarate dehydrogenase is similar to the pyruvate dehydrogenase complex. It requires thiamine, lipoic aicd, CoA, FAD and NAD. Lack of thiamine slows oxidation of acetyl-CoA in the TCA cycle.

3. Succinyl-CoA synthetase catalyses a substrate-level phosphorylation of GDP-->GTP

4. Succinate dehydrogenase is on the inner mitochondrial membrane, where is also functions as complex II of the electorn trasport chain

5. Citrate synthase condenses the incoming aceyl-group with Oxaloacetate to form citrate

Several intermediates of the cycle may serve other function:中間產物和其他反應的連接

1.Citrate may leave the mitochondria(citrate shuttle)to deliver acetyl-CoA into the cytoplasm for fatty acid synthesis

2.Succinyl-CoA is high energy intermediate that can be used for heme synthesis and to activate ketone bodies in exrtrahepatic tissues.

3.Malate can leave the mitochondira(malate shuttle) for gluconeogenesis

4. OAA:early intermediate molecule in gluconeogenesis and subtrate for amino acid synthesis

5.alfa-glutarate: subtrate of amino acid synthesis

Yield of the TCA cycle:Two CO2, 3 NADH, 1 FADH2, One GTP

 NADH在電子傳遞鏈約釋放 3ATP(or 2.5), FADH2約2ATP(or1.5) 

所以一個 acetyl-CoA約可產生12(or 10)ATP

補充bio-chemical card:

citrate synthase也可被ATP, NADH and succinyl-CoA抑制

alfa-ketoglutarate dehydrogenase可被ATP or GTP, NADH, syccinyl CoA抑制

總之可借由這些細胞的能量來抑制此循環的進行。

When intermediates are drawn out of the TCA cycle, the cycle slows. Therefore, when intermediates leave the cycle they must be replaced to ensure sufficient energy for the cell.

由此可看到細胞在葡萄糖缺乏時仍然可以由脂肪酸 氨基酸 酮體等中間物來產生acetyl-CoA來產生能量，讓身體不至於缺乏能量。

當然每一個反應又是另一個學問，不過人體其實是非常奧妙的，由荷爾蒙把這些物質的分解和儲存調控的恰到好處！當出現問題時，疾病也就產生了。

有趣的就是這個反應不由荷爾蒙所調控，而是由能量狀態來調控。這應該也是一個重點。