Oxygen consumption

Oxygen usage

Most of the oxygen is used to produce ATP in oxidative phosphorylation pathway in mitochondria. Citric acid cycle (CAC) in the mitochondrial matrix provides cells with essential precursors for synthesis of amino acids and other molecules, and NADH, FADH2, and succinate for the oxidative phosphorylation pathway. Fatty acids are broken down in beta oxidation in the inner mitochondrial membrane to produce acetyl-CoA for the CAC. Inner mitochondrial membrane contains the components of electron transport chain, where electrons are transferred in redox reactions from NADH to oxygen.

Mitochondrial metabolism produces CO2, about 2 dL/min. Normal respiratory quotient (rate of CO2 production divided by rate of O2 consumption) is 0.8; respiratory quotient shifts to 1 on carbohydrate diet and to 0.7 on a fat diet.

Small amounts of oxygen are also needed in other metabolic processes, including in the production of nitric oxide by NO synthases, in cholesterol synthesis, and hydroxylation of collagen.

Oxygen transport

The vascular system transports oxygen from the lungs to the tissues in red blood cells (RBCs), bound to haemoglobin (Hb). Less than 2% of oxygen is transported through the skin, and mainly used in the skin.

O2 is readily dissolved and diffused in lipid bilayers, and cell membranes are not barriers to oxygen diffusion (Subczynski et al., 1992 and 1998). O2 water solubility is low, 8.3 mg/L at room temperature. In addition, aquaporins, especially AQP1 transport gases, including O2, across membranes. The blood-to-brain permeability of O2 is even higher than that of water (Kassissia et al., 1995. Also myocardial capillaries are more permeable to oxygen that to water (Rose & Goresky, 1985). Inside the myocytes of skeletal muscle and cardiac muscle another oxygen binding protein, myoglobin (Mb) facilitates the transport of oxygen to mitochondria.

The solubility of O2 is highest in the centre of lipid bilayer, and the diffusion of oxygen to the binding site of cytochrome c oxidase (COX) at the centre of the inner mitochondrial membrane bilayer is the last step of oxygen transport in the respiratory cycle.

Neuroglobin

Neuroglobin (Ngb) is a monomeric protein (151 amino acids, 17 kDa) that was found in human and mouse brain (hence the name), but it is expressed also in some endocrine tissues, and in very low concentrations in most tissues and organs. Due to the low concentration (on average <1 µM in mouse brain), its role in oxygen transport or storage is negligible, except in places such as retinal ganglion cell layer and the optic nerve, where Ngb concentration can be 50-200 fold higher. Ngb expression is increased in oxidative injuries, including hypoxia and ischemia, possibly functions as NO scavenger, and protects tissue from further damage and necrosis (Fiocchetti et al., 2017). In CNS, Nbg is mainly expressed in neurons, especially in the hypothalamus, and in activated astrocytes.

Neuroglobin hosts heme-Fe2+/3+ as prosthetic group, so that Fe-ion is either hexa- or penta-coordinated, and the penta-coordinate form can bind the typical gaseous heme ligands. Binding of O2, NO, CO, etc is allosterically modulated, and causes a structural change in the Ngb molecule. It has a complex interaction network with intracellular proteins, including the α-subunit of G proteins and voltage-dependent anion channel (VDAC).

Intracellularly, Ngb resides mainly in the cytosol, but in addition both functionally and physically associated with mitochondria and other mitochondria-associated proteins. Nbg has a direct impact on the mitochondrial apoptotic pathway (Fiocchetti et al., 2017).

Cytoglobin

Cytoglobin (Cygb) is expressed in most tissues in fibroblast-like cells, and also in CNS. Cybg expression is up-regulated in hypoxia, at least in the liver, and skeletal and cardiac muscle, but also in the brain (Hundahl et al., 2013; Reuss et al., 2016). Cygb is found in smooth muscle cells of the blood vessels, where its expression is up-regulated by inflammatory cytokines (Jourd'heuil et al., 2017).

Cytoglobin has significant NO dioxygenase activity: O2 bound to Cygb reacts with NO, producing nitrate; ferric state of Cygb is the rapidly restored by a reduction system involving NADH and cytochromes (Thuy et al., 2016; Amdahl et al., 2017). This way cytoglobin regulates blood pressure and vascular tone in the vascular walls (Liu et al., 2017).

VO2max

VO2max is the maximal oxygen consumption (maximal aerobic capacity, peak oxygen uptake), expressed either as L O2/min or per body mass, mL O2/(kg×min). VO2max reflects cardiorespiratory fitness (CRF); low CRF is associated with high risk of cardiovascular disease (CVD) and mortality. The VO2max of average untrained healthy males is ∼35-40 mL O2/(kg×min). In endurance athletes it may be close to 100 mL O2/(kg×min).

VO2max is measured in an incremental exercise test, usually on a cycle ergometer, while measuring ventilation and O2 and CO2 in the inhaled and exhaled air. Maximal oxygen consumption is reached when oxygen consumption stops increasing with increased workload. Calculation is based on the Fick principle:

, where CO is the cardiac output, and [O2]a and [O2]v are the O2 concentrations in arterial and venous blood, respectively. In practise, VO2max is often estimated based on other tests, such as 6-min walk test (Mänttäri et al., 2018).

Measurement of oxygen consumption

Oxygen consumption in tissue (metabolic rate of oxygen, MRO2) can be calculated from tissue perfusion (f, blood flow), oxygen extraction fraction, OEF, equalling the oxygen concentration difference in venous and arterial blood, and the concentration of oxygen in the arterial blood, [O2]a:

Oxygen concentration in blood is usually reported by laboratories in units mL O2 in one litre of blood. The molar volume of ideal gas, 22.4 L/mol, is used to convert O2 volume into molar units. O2 concentrations in arterial blood are normally ∼200 mL/L, or ∼9 mM (mmol/L). Haemoglobin (Hb) concentration in the blood is a primary determinant of the [O2]a.

[15O]O2 PET has been used to assess oxygen consumption especially in the brain and heart.

QSM MRI can quantify changes in deoxyhaemoglobin content in the blood and venous oxygen saturation (SvO2) in the brain and peripherally (Fan et al., 2015; Finnerty et al., 2018).

[1-11C]acetate PET has been used for assessment of oxidative metabolism.


See also:


Literature

Baron J-C, Jones T. Oxygen metabolism, oxygen extraction and positron emission tomography: historical perspective and impact on basic and clinical neuroscience. NeuroImage 2012; 61: 492-504. doi: 10.1016/j.neuroimage.2011.12.036.

Kety SS. Determinants of tissue oxygen tension. Fed Proc. 1957; 16(3): 666-671. PMID: 13480339.

Popel AS. Theory of oxygen transport to tissue. Crit rev Biomed Eng. 1989; 17(3): 257-321. PMCID: PMC5445261.

Subczynski WK, Hopwood LE, Hyde JS. Is the mammalian cell plasma membrane a barrier to oxygen transport? J Gen Physiol. 1992; 100(1): 69-87. doi: 10.1085/jgp.100.1.69.

Subczynski WK, Hyde JS. Membranes - barriers or pathways for oxygen transport. Adv Exp Med Biol. 1998; 454: 399-408. PMID: 9889917.



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Updated at: 2019-10-29
Created at: 2018-04-08
Written by: Vesa Oikonen