This document discusses the metabolism and energy utilization of cardiac muscle cells. It notes that the heart has an extraordinarily high energy demand to power contraction. The heart predominantly uses fatty acids and glucose as fuel, which are broken down to acetyl-CoA and fed into the Krebs cycle to power oxidative phosphorylation and ATP production. Energy is stored short-term in ATP and long-term in creatine phosphate. Contraction results from calcium binding to troponin, releasing the inhibitory effect on actin-myosin cross-bridging and shortening of sarcomeres.
This document discusses the metabolism and energy utilization of cardiac muscle cells. It notes that the heart has an extraordinarily high energy demand to power contraction. The heart predominantly uses fatty acids and glucose as fuel, which are broken down to acetyl-CoA and fed into the Krebs cycle to power oxidative phosphorylation and ATP production. Energy is stored short-term in ATP and long-term in creatine phosphate. Contraction results from calcium binding to troponin, releasing the inhibitory effect on actin-myosin cross-bridging and shortening of sarcomeres.
This document discusses the metabolism and energy utilization of cardiac muscle cells. It notes that the heart has an extraordinarily high energy demand to power contraction. The heart predominantly uses fatty acids and glucose as fuel, which are broken down to acetyl-CoA and fed into the Krebs cycle to power oxidative phosphorylation and ATP production. Energy is stored short-term in ATP and long-term in creatine phosphate. Contraction results from calcium binding to troponin, releasing the inhibitory effect on actin-myosin cross-bridging and shortening of sarcomeres.
92 Chapter 3. Pathophysiology of the cardiovascular system ( I. Hulı́n, F. Šimko et al.
specific arrangement of actin and myosin filaments 1. energy production
which telescopically slide in between each other thus 2. energy storing forming a number of characteristical lines and bands. Regarding the proper comprehension of function, the 3. energy utilization most important are the Z-lines. They issue thin actin filaments and at the same time demarcate the bor- 3.2.1 Energy production ders of sarcomeres. The distance between two Z-lines represents the length of the sarcomere. The diastolic Myocardium is able to produce energy from sev- length of the latter varies between 1,5–2,2µm. Short- eral substrates: fatty acids, glucose, lactate, pyru- ening of muscles is realized by the procedure of tele- vate, ketone bodies and even aminoacids. Preference scopic insertion of thin myosin filaments in between of individual substrates representing the particular thick myosin filaments thus shortening the distance sources of energy depends on their current concen- between Z-lines and the sarcomere itself. tration in both blood and cardiac muscle cells. This Several myofibrils form one functional unit, in determines the concentration gradient of the given which the Z-lines of individual sarcomeres precisely substrate on the level of cardiomyocyte membrane. align each other. Aside from the concentration gradient, the selection of substrates is also determined by natural capacity of particular enzymatic systems of the cardiac muscle cell, which limitates predominantly the utilization of atypical sources of energy also in case of their high concentration in blood. 3.2 Metabolism of cardiac If the oxygen supply is sufficient, the dominant muscle cell fuel is represented by fatty acids which are predom- inantly utilised and they cover 50-70 % of the to- tal energy demands myocardium, and glucose which covers the remnant 30 %. Lactate is utilized as an The contractile function of the heart is a process energy substrate under the condition of increased with extraordinarily high energy demand. Oxygen muscular activity, during which the lactate concen- consumption in the beating heart depends on three tration in blood augments rapidly. Ketone bodies main factors wall stress, contractile state of my- and aminoacids are utilized exclusively under spe- ocardium and freqency of contractions. Although cial pathological conditions (e.g. in diabetic ketoaci- the weight of the heart mass represents merely 1 % dosis). They participate in ATP production by more of the body weight (in adults), the myocardium con- than 10 %. sumes app. 10 % of the total body oxygen consump- The process of the splitting of each of the men- tion. The heart is a typical aerobic organ with a tioned substrates provides a common intermediate minimal ability to work under oxygen debt. The product – acetyl KoA. In the case of fatty acids it is amount of energy consumed during systole must be formed by their splitting in the process of beta oxi- inevitably re-supplied during the diastolic recovery dation. Glucose is by means of glycolysis or pentose period. An adequate and fluent supply of cardiac cycle converted to pyruvate and the subsequent ox- muscle cells with oxygen and substrates is inevitable idative decarboxylation converts pyruvate to acetyl- in order to replenish the consumed energy.It is to KoA. The latter is formed also during the processing say, that already under rest conditions the extrac- of lactate, ketone bodies and aminoacids. tion of oxygen from arterial blood is almost maximal. The common intermediate product of all these re- Therefore when heart activity increases, the augmen- actions, the acetyl - KoA, enters the Krebs cycle in tation of oxygen supply takes place almost exclu- mitochondria where it is split to CO2 and hydrogen. sively by means of the increase of coronary blood The latter is subsequently processed in the process of flow. oxidative phosphorylation. It is a sequence of reac- During each cardiac revolution the energy expen- tions in which the cellular respiration (oxidation) is diture takes place in three phases which are tightly couppled with energy in form of ATP (phosphoryla- bound (see fig. 3.7 on page 93): tion). Cellular respiration represents the transfer of 3.2. Metabolism of cardiac muscle cell (F. Šimko) 93
Figure 3.7: Metabolism of cardiomyocyte
94 Chapter 3. Pathophysiology of the cardiovascular system ( I. Hulı́n, F. Šimko et al.)
hydrogen onto oxygen within the respiratory chain,
thus forming H2 O. Simultaneously, phosphorylation is carried out, which means that energy produced by 3.3 Contraction-relaxation cy- means of respiration and liberated in a cascade-like manner is being bound gradually by the conversion cle of ADP+Pi to ATP. 36 to 38 molecules of ATP are produced by pro- cessing of 1 molecule of glucose in the mentioned aerobic manner. Processing of 1 molecule of fatty The most specific property of the cardiac muscle acid results in a several-fold higher ATP production, is the ability to contract. the particular value of which depends on the chain Contraction is a complex process which is rep- length of the particular fatty acid. resented by a precisely balanced interaction be- tween contractile proteins (actin, myosin and tropomyosin), calcium ions, cellular transportation 3.2.2 Energy storing systems of calcium (sarcolemma, sarcoplasmic retic- The energy within heart muscle is stored in form ulum, mitochondria) and high energy phosphates of two basic macroergic compounds – adenosine (ATP, KP). The initial step in this complex reac- triphosphate (ATP) and kreatin phosphate (KP). tion is the origin of action potential (excitation) and ATP serves as a prime energy donor for the process the resultant action is the shortening of muscular of contraction as well as for energetically dependent fibers (contraction). transportation membrane systems (ATP-ases). KP The thick filaments of myosin and thin filaments is a substance which stores energy. Under the condi- of actin are the proper elements of contraction. Tro- tion of a fluent and sufficient supply with oxygen and ponin is firmly bound with tropomyosin thus forming substrates, the ADP and Pi formed by splitting are one functional unit, troponin-tropomyosin complex. resynthetized to ATP and the energy necessary for The latter participates in contraction as a regulatory this resynthesis is provided from kreatinphosphate. protein. During diastole, the troponin-tropomyosin The ATP level is preserved while the cytoplasmic complex is firmly bound on actin and thus inhibits level of KP, representing a form of stored energy, de- chemical interaction between actin and myosin. The creases. When energetic situation improves, KP is surface of troponin contains a receptor which is able replenished by energy from the respiratory chain. to bind calcium. Providing this site is not occupied The store of kreatinphosphate in the cardiac mus- by calcium ion, the troponin-tropomyosin complex is cle is relatively small and can preserve the ATP level in a position which inhibits the chemical interaction merely for a relatively short period of time. A severe between actin and myosin. Such a situation super- ischemia finally implies a decrease of ATP and thus venes during diastole. During excitation (during the a decrease of cardiac muscle function. plateau period of action potential) which closely pre- Besides its store function, kreatinphosphate plays cedes the systole, the cytoplasmic concentration of the role of a transporter of energy from mitochondria calcium elevates. Calcium is bound with troponin. toward myofibrils. ATP, that is to say, originates in Thus the troponin-myosin complex is released from mitochondria, but is being utilized in other intracel- the binding with actin. In this way the inhibitory ef- lular sites – predominantly in myofibrils. fect of troponin-myosin complex on actin is removed, and chemical interaction between actin and myosin 3.2.3 Energy utilization takes place. The clubbed molecules of myosin after being bound with actin are leant thus shifting actin Energy is utilized in the process of contraction which and myosin filaments propel in mutually opposit di- is going to be explained in the following chapter. rections. According to the sliding theory the actin filaments slide telescopically between the myosin fil- aments while the length of either of filaments is not changed. This process is manifested as contraction. Hence, in this difficult process, calcium plays an im- portant role of being the contraction inducer.