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Review
. 2019 Jun 18;8(12):e012673.
doi: 10.1161/JAHA.119.012673. Epub 2019 Jun 12.

Glucose Metabolism in Cardiac Hypertrophy and Heart Failure

Diem H Tran  1 , Zhao V Wang  1
Affiliations
Review

Glucose Metabolism in Cardiac Hypertrophy and Heart Failure

Diem H Tran et al. J Am Heart Assoc. .
No abstract available

Keywords: glucose metabolism; heart failure; ischemic heart disease; pathological cardiac remodeling.

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Figures

Figure 1
Figure 1
Glucose metabolic pathways in the heart. In cardiomyocytes, glucose is transported through glucose transporters GLUT1 or GLUT4. Polyol pathway‐derived sorbitol and fructose may be converted to AGEs or fructose 6‐P for glycolytic use. Intracellular glucose can be phosphorylated to glucose 6‐phosphate by hexokinase (HK). Glucose 6‐phosphate is then metabolized bv multiple pathways, including glycolysis, pentose phosphate pathway (PPP), and hexosamine biosynthetic pathway (HBP). In the cytosol, pyruvate can be utilized to form alanine or lactate. In mitochondria, pyruvate is converted to acetyl‐CoA for the tricarboxylic acid cycle. Ribulose 5‐P derived from PPP can be used for pyrimidine/purine synthesis or converted into intermediates of glycolysis. UDP‐GlcNAc, the final product of HBP, serves as a substrate for the synthesis of proteoglycans, hyaluronan, glycolipid, GPI anchor, O‐GlcNAc modification, and N‐glycan. AGEs indicates advanced glycation end products; fructose 6‐P, fructose 6‐phosphate; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; GPI, glycosylphosphatidylinositol; O‐GlcNAc, O‐linked β‐N‐acetylglucosamine; ribulose 5‐P, ribulose 5‐phosphate; UDP‐GlcNAc, uridine diphosphate N‐acetylglucosamine.
Figure 2
Figure 2
The glycolysis pathway in the heart. A series of enzymatic reactions of glycolysis convert glucose to pyruvate, which may be reduced to lactate or further catabolized by the TCA cycle. Glycolysis‐derived ATP plays a crucial role in maintaining the contractile function of the heart. The green arrow indicates activation of PFK1 by fructose 2,6‐biphosphate. ALT indicates alanine transaminase; fructose 1,6‐BP, fructose 1,6‐bisphosphate; fructose 2,6‐BP, fructose 2,6‐bisphosphate; fructose 6‐P, fructose 6‐phosphate; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; HK, hexokinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PFK, phosphofructokinase; PK, pyruvate kinase; TCA, tricarboxylic acid.
Figure 3
Figure 3
The polyol pathway in the heart. In the polyol pathway, aldose reductase (AR) converts glucose to sorbitol, which is subsequently oxidized to fructose by sorbitol dehydrogenase (SDH). AR also acts as an antioxidant enzyme by catalyzing toxic aldehyde to nontoxic alcohol. AGEs indicates advanced glycation end products; fructose 6‐P, fructose 6‐phosphate; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; GLUT, glucose transporter; GR, glutathione reductase; GSH, reduced glutathione; GSSG, oxidized glutathione; ROS, reactive oxygen species.
Figure 4
Figure 4
The pentose phosphate pathway in the heart. The oxidative phase of the pentose phosphate pathway (PPP) generates NADPH and ribulose 5‐phoshpate (ribulose 5‐P), which are mainly used for anabolism. The nonoxidative phase of PPP stimulates the interconversion of 5‐carbon sugars with a series of reversible reactions. Whereas acute activation of the PPP confers cardioprotection against oxidative stress, persistent upregulation of the PPP may exacerbate oxidative damage and contribute to cardiomyopathies. 6GPD indicates 6‐phosphogluconate dehydrogenase; fructose 6‐P, fructose 6‐phosphate; G6PD, glucose 6‐phosphate dehydrogenase; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; HK, hexokinase; ribose 5‐P, ribose 5‐phosphate; xylulose 5‐P, xylulose 5‐phosphate.
Figure 5
Figure 5
The hexosamine biosynthetic pathway (HBP) in the heart. The rate‐limiting enzyme of the HBP, GFAT, converts fructose 6‐P and glutamine to glucosamine 6‐phosphate, which is used to generate the final product, UDP‐GlcNAc. UDP‐GlcNAc is a substrate for various biosynthetic pathways, including glycan synthesis, glycerolipid production, etc. UDP‐GlcNAc is also used for a prominent posttranslational protein modification on Ser/Thr sites by O‐GlcNAc transferase (OGT), which is counteracted by O‐GlcNAcase (OGA) to catalyze the removal of O‐GlcNAc. GFAT indicates glutamine:fructose 6‐phosphate amidotransferase; GLUT, glucose transporter; HK, hexokinase; UDP‐GlcNAc, uridine diphosphate N‐acetylglucosamine.
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